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10 Best Probiotics For Depression & Anxiety: Gut-Brain Axis Modification

Microbiota is classified as an ecological community of microorganisms that share a specific host.  Within the human body it is estimated that there are trillions of microorganisms, accounting for approximately 1% to 3% of total body mass; equating to an average net weight of around 3 lbs.  Though scientists these days are attempting to elucidate the importance of specific microorganisms and combinations within the human body, research in this field is relatively complex.

Additionally, compared to other areas of health research, the human microbiota – particularly within the gut – never received as much attention as it may have warranted; hence the reason it is now commonly referenced as the “forgotten organ.”  It wasn’t until the late 1990s that scientists began ambitiously investigating the implications of gut bacteria on immune function.  From the 1990s to present day, researchers have managed to unravel links between gut bacteria and numerous conditions including: arthritis, cancer, diabetes, fibromyalgia, multiple sclerosis, and obesity.

Though we know that the gut microbiota mediates propensity to develop deleterious general health conditions, there’s increasing evidence that it may affect a person’s psychological state (e.g. mood, anxiety level, etc.).  Abnormally high concentrations of specific microorganisms in the gut are now linked to major depression, whereas others are associated with better moods.  This has lead many experts to speculate that supplementation with single and/or multi-strain probiotics may attenuate symptoms of depression and anxiety, while simultaneously improving general health.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/16819463

10 Best Probiotics for Depression & Anxiety: Bacterial Strains

Included below are 10 strains of probiotics supported by science to improve depression and anxiety.  Keep in mind that not all of these strains have been clinically evaluated in humans – many have only been assessed in animal models (e.g. rats/mice).  For this reason, we cannot automatically assume that they will prove efficacious among humans, particularly those with severe depression and/or anxiety.  Moreover, until further research is conducted, no probiotic should be regarded as a replacement for scientifically-supported, first-line antidepressants and anxiolytics.

  1. Bifidobacterium Longum

This is a Gram-positive, catalase-negative, rod-shaped bacterium found in the GI tract of humans.  It is one of 32 species associated with the Bifidobacterium genus and implicated in many processes within the human body.  Specifically, Bifidobacterium longum inhibits growth of pathogenic species and maintains normative function of the gastrointestinal tract.

Studies have shown that it may decrease lactose intolerance, prevent diarrhea, attenuate food allergies, and have an antioxidant effect.  Other research indicates that Bifidobacterium longum may lower cholesterol, reduce tumor growth, and may decrease likelihood of certain cancers (e.g. colorectal).  In addition to evidence suggesting that Bifidobacterium longum improves a person’s general health, there’s research indicating that it may be beneficial for mental health.

Particularly, research in animal models shows that Bifidobacterium longum significantly reduces symptoms of anxiety.  It accomplishes this in a number of ways, but is believed to alter neural function via its action upon the vagal nerve.  Bifidobacterium longum mediates vagal tone and as a result, reduces symptoms of anxiety in mice.

Its effect upon vagal function was pinpointed by researchers who removed the vagus nerve (via a vagotomy) from mice.  Mice without the vagus nerve experienced no changes in anxiety following administration of Bifidobacterium longum.  It is logical to assume that similar gut-vagal-brain innervations occur in humans administered this particular probiotic strain.

The evidence is not limited to support the therapeutic effects of Bifidobacterium longum is not confined to a standalone mouse study.  Another study involved administration of Bifidobacterium longum to rats following parasitic infection with Trichuris muris.  Trichuris muris altered neurophysiological function in such a way that important biomarkers such as hippocampal BDNF (brain-derived neurotrophic factor) were nearly depleted.

Abnormally low BDNF is associated with a multitude of neuropsychiatric conditions, perhaps most prominently, major depression.  Upon administration of Bifidobacterium longum after parasitic infection, rats exhibited significant increases in BDNF – this is associated with an antidepressant response.  Perhaps administration of this probiotic strain in humans may be beneficial for mood while simultaneously reducing anxiety.

Fortunately, research of Bifidobacterium longum was also conducted in human volunteers.  A two-part study assessed the effect of Bifidobacterium longum when administered with Lactobacillus helveticus in both animal models and humans.  The first part of the study with the animal models (rats) demonstrated that the combination of Bifidobacterium longum with Lactobacillus helveticus significantly reduced anxiety (as evidenced by a defensive burying test).

The second part of the study with human participants discovered that the concurrent Bifidobacterium longum with Lactobacillus helveticus improved scores on numerous clinical measures.  Measures of significant improvement included: Hopkins Symptom Checklist (HSCL-90), Hospital Anxiety and Depression Scale (HADS), Coping Checklist (CCL), and urinary free cortisol (UFC).  It was concluded that the combination of these probiotics exhibit anxiolytic and therapeutic effects conducive to psychological health.

However, it remains unclear as to whether Bifidobacterium longum necessitates the presence of Lactobacillus helveticus for a clinically significant anxiolytic or antidepressant effect in humans.  Further research of this strain in animal models was published in 2014 by Savignac et al. who assessed the effects of Bifidobacterium longum compared to Celexa (a pharmaceutical SSRI) among BALB/c mice.

The BALB/c mice were administered Bifidobacterium longum (strain) 1714, Celexa, another Bifidobacterium strain, or a placebo – each for a duration of 6 weeks.  Behavioral measures were conducted in a stress-induced hyperthermia test, marble burying task, elevated plus maze, open field assessment, tail suspension test, and forced swim test.  Physiological markers of stress were also collected from each of the mice.

Results indicated that Bifidobacterium longum 1714 (and the other strain) and Celexa reduced anxiety on the marble burying test.  However, only Bifidobacterium longum 1714 decreased stress-induced hyperthermia and facilitated an antidepressant response on the tai suspension test.  This evidence supports the idea that Bifidobacterium longum 1714 decreases anxiety and may improve mood among anxious animal models.

Another study published by Savignac et al. (2015) documented the ability of Bifidobacterium longum to modulate cognitive processes among BALB/c mice with anxiety.  Adult BALB/c mice were fed Bifidobacterium longum 1714, another probiotic strain (B. breve 1205) or a control (vehicle treatment) for 11 weeks.  After 4 weeks of administration, assessments were conducted to evaluate cognitive function, locomotor activity, and visceral pain.

Mice administered Bifidobacterium longum 1714 exhibited quicker object recognition and made fewer errors within a Barnes maze than mice receiving other interventions.  From this study, researchers were able to conclude that not all Bifidobacterium subspecies elicit equal neurophysiological effects.  Moreover, administration of Bifidobacterium longum 1714 (in particular) is associated with cognitive enhancement among mice with anxiety.

From the culmination of research assessing the neurophysiologic effects of Bifidobacterium longum, we can conclude that it may improve symptoms of depression and anxiety among humans.  Additionally, individuals with anxiety (and possibly those without) may derive additional cognitive enhancement from the Bifidobacterium longum 1714 strain.  If your goal is to reduce anxiety and depression via modifying your gut, you may want to consider regular supplementation with Bifidobacterium longum.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20600016/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20974015/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25251188
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25794930
  1. Lactobacillus Rhamnosus

Lactobacillus rhamnosus is a Gram-positive, anaerobic rod that commonly appears in chains.  Initially it was thought to be a member of the Lactobacillus casei species, but additional investigation would reveal its status as a standalone species.  Preliminary research has documented its therapeutic efficacy for a variety of conditions including: preventing peanut allergies, reducing diarrhea, treating dermatitis, genital tract infections, and obesity.

In animal models, Lactobacillus rhamnosus has been shown to attenuate symptoms of depression and anxiety.  A study published in 2011 specifically documented the effect of Lactobacillus rhamnosus upon neurotransmitter systems within the central nervous system.  The study discovered that chronic administration of Lactobacillus rhamnosus to mice altered the neurotransmission of GABA (gamma-aminobutyric acid), an important inhibitory neurotransmitter.

They noted that GABA biomarkers were upregulated in certain regions and downregulated in others, indicative of significant neural changes resulting from the probiotic.  Regions in which GABAergic transmission was modified following Lactobacillus rhamnosus ingestion included the: amygdala, cingulate, hippocampus, locus coeruleus, and prefrontal cortex.  Like the aforementioned Bifidobacterium longum strain, Lactobacillus rhamnosus exerted its effect upon the brain through the vagal nerve.

This specifically lead to modified neurotransmission of GABA, which was ultimately associated with decreased anxiety and depression in the animal models.  Whether similar antidepressant and anxiolytic effects can be attained by chronic administration of Lactobacillus rhamnosus in humans isn’t known.  That said, the preliminary evidence suggests that it is likely to provide some sort of benefit.

It should be noted that in a small percentage of the population, probiotic therapy with Lactobacillus rhamnosus has lead to sepsis, a condition characterized by tissue and organ injuries resulting from the body’s innate response to infectious pathogens.  While sepsis only occurs in a small percentage of the population, particularly those with compromised immune function, it should be noted as a potential adverse reaction.  That said, the potential antidepressant and anxiolytic benefits of Lactobacillus rhamnosus among non-immunocompromised populations likely outweigh the small risk of sepsis.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21876150/
  1. Lactobacillus Helveticus

Lactobacillus helveticus is a bacterium named after “Helvetia,” a Latin reference to the national female goddess of Switzerland.  This particular bacterium is rod-shaped, belongs to the genus Lactobacillus, and facilitates production of lactic-acid.  It is perhaps most well-known for being utilized to enhance the production of cheeses (e.g. Swiss, Cheddar, Parmesean, etc.) by inhibiting bitter taste and optimizing flavors.

Preliminary research of Lactobacillus helveticus suggests that it may reduce blood pressure with a similar mechanism to ACE inhibitors.  Additionally, this appears to be yet another strain of bacteria that, when supplemented as a probiotic, alleviates symptoms of depression and anxiety.  One study investigated the effect of Lactobacillus helveticus administration to animal models exhibiting hyperammonemia.

Hyperammonemia or excessive ammonia within the bloodstream is considered dangerous in that it can inflict severe brain damage and ultimately cause death.  Animal models were made hyperammonemic via injections of ammonium acetate for 4-weeks.  This caused significant neuroinflammation and altered neurotransmission, particularly of serotonin.

Thereafter, they treated the rats with the probiotic Lactobacillus helveticus (strain NS8).  Results indicated that the rats treated with Lactobacillus helveticus experienced significant changes in biomarkers.  More specifically, the Lactobacillus helveticus NS8 strain decreased neuroinflammation, reduced serotonin metabolism, decreased anxiety, and restored cognitive function.  A second study published in 2013 assessed the interaction between diet, gut microbiota, and genetics of mice.

Wild-type (WT) and IL-10 deficient mice were placed on either: a standard mouse feed vs. Western-style diet (33% fat and 49% carbs) plus Lactobacillus helveticus probiotics for 21 days.  Throughout the study, researchers collected biomarker data and measured anxiety along with spatial memory function.  Thereafter, they tested microorganism content within fecal excrement of the mice to determine how quantities of microorganisms affected various measures.

Results indicated that all mice (regardless of whether WT or IL-10) eating the Western diet had weight gain along with anxiety and increased cytokine expression (signifying inflammation).  It appeared as though Lactobacillus helveticus administration attenuated anxiety and memory deficits associated with Western diet consumption and also reduced anxiety among WT mice on a standard mouse feed diet.  Mice with less inflammation responded better to the probiotic than those with high inflammation.

Nonetheless, this provides evidence to support the therapeutic potential of Lactobacillus helveticus in reducing anxiety and correcting cognitive deficits.  Currently, it is unclear as to what the effects of Lactobacillus helveticus are in humans, particularly healthy ones.  That said, Lactobacillus helveticus may reduce inflammation and mediate serotonergic transmission – possibly eliciting an anxiolytic and/or antidepressant response.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24554471
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23566632
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23181058
  1. Lactobacillus Plantarum

Lactobacillus plantarum is a bacterium that was first isolated from human saliva and is ubiquitous in fermented foods such as: sauerkraut, pickles, and kimchi.  It is a member of the Lactobacillus species and may have numerous therapeutic effects in humans.  Preliminary evidence suggests that it may decrease soy allergies, attenuate adverse viral effects of HIV, and reduce inflammatory biomarkers throughout the body.

A study suggests that Lactobacillus plantarum is capable of enhancing memory, possibly acting as a nootropic and/or neuroprotective agent.  This study involved assessing the effects of Lactobacillus plantarum C29 in a sample of 344 aged Fischer rats.  Researchers administered each of the probiotic strains orally once per day, 6/7 days per week, for a total of 8 weeks.

Results indicated that Lactobacillus plantarum C29 strains restored age-reduced cognitive function, minimized escape latency time (on task), and increased swimming times – compared to a control group.  Biomarkers had been altered among the rats receiving Lactobacillus plantarum as well, namely: doublecortin (DCX), brain-derived neurotrophic factor (BDNF), and cAMP response element binding protein (CREB) activation.  Lactobacillus plantarum also altered expression of: p16, cyclooxygenase-2, mTOR, NF-kappa-beta, Akt, and nitric oxide synthase.

It is understood that deficits in BDNF are associated with major depression, as are upregulated inflammatory biomarkers.  Lactobacillus plantarum appears to increase BDNF and decrease inflammation, thereby improving neuropsychiatric function in animal models.  While this specific strain hasn’t been evaluated in humans, it may confer similar benefits to those observed in the trial with aged rats.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25598393
  1. Bifidobacterium Animalis

Bifidobacterium animalis is a bacterium localized principally within the large intestines of humans with Gram-positive, anaerobic, and rod-shaped features.  This probiotic is commonly found within dairy products, but also appears within an array of foods and dietary supplements.  Though the health benefits of Bifidobacterium animalis aren’t clear, initial studies suggest it may reduce bloating and intestinal discomfort associated with IBS (irritable bowel syndrome).

However, the thereapeutic potential of Bifidobacterium animalis is not limited to those with IBS.  It appears as though this species acts as an antioxidant by reducing oxidative stress, while simultaneously decreasing enzymatic activity of monoamine oxidase.  Assuming it is an effective antioxidant, it may inhibit and/or reduce neuroinflammation resulting from heightened oxidative stress.  The reduction in neuroinflammation has potential to decrease likelihood of anxiety, depression, and possibly interfere with the pathogenesis of certain diseases.

What’s equally exciting as the antioxidative properties associated with Bifidobacterium animalis is its ability to inhibit activity of MAO (monoamine oxidase).  Inhibition of MAO allows neurotransmitters (serotonin, dopamine, norepinephrine) to remain in the synaptic cleft for a longer duration without being scavenged by the monoamine oxidase enzyme.  As a result, this improves neuronal signaling and possibly the user’s mood and/or anxiety.

The potency of Bifidobacterium animalis’ MAO inhibition is unclear, however, an entire class of antidepressants (the MAOIs) function with this exact mechanism.  A 2011 study assessed the activity of Bifidobacterium animalis (strain 01) in vitro and in vivo among aging mice.  Results from this study indicated that Bifidobacterium animalis scavenged free radicals and decreased MAO activity.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21132298
  1. Lactobacillus Casei

Lactobacillus casei is a species of bacterium that inhabits the intestine and oral mucosa of humans.  The presence of Lactobacillus casei is considered complementary and conducive to the growth of Lactobacillus acidophilus, another healthy bacterium.  Industrially, Lactobacillus casei is often utilized to aid in the production of dairy products such as cheeses.

Medically, some evidence indicates that Lactobacillus casei strains such as “Shirota” may inhibit Helicobacter pylori growth to a small extent.  Certain strains of Lactobacillus casei may be useful as an intervention for pathogenic bacterial diseases affecting the gastrointestinal tract.  Usage of Lactobacillus casei along with various other healthy bacteria (in the form of a multistrain probiotic) has been successful in preventing antibiotic-associated diarrhea (AAD) and Clostridium difficile infections (CDIs).

A study published in 2009 by Rao et al. investigated the Lactobacillus casei Shirota (LcS) strain as an intervention for chronic fatigue syndrome.  Patients with chronic fatigue syndrome are understood to exhibit abnormal densities of microorganisms within the gut flora and commonly experience significant anxiety.  For this reason, researchers recruited 39 individuals diagnosed with chronic fatigue syndrome and organized a study to administer either: LcS (Lactobacillus casei Shirota) with 8 billion colony forming units (CFUs) or a placebo – once per day for 2 months.

Stool samples were collected from patients prior to commencement and following the study.  Neuropsychiatric states were assessed with the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) pre- and post-study.  Results indicated that there were significant differences in stool bacteria among those receiving the probiotic compared to those taking the placebo.

Those who had received the probiotic exhibited significant increases in Lactobacillus and Bifidobacteria bacteria within excrement compared to the placebo controls.  Additionally, there were significant changes on BAI (Beck Anxiety Inventory) scores among those receiving the Lactobacillus casei Shirota (LcS) strains compared to the controls.  Researchers concluded that administration of Lactobacillus casei Shirota (LcS) appears to improve colonic health and symptoms of anxiety among those with chronic fatigue syndrome (CFS).

The Lactobacillus casei Shirota (LcS) administration elevated concentrations of Bifidobacteria, which may have contributed largely to the therapeutic effects.  Bifidobacteria are reportedly capable of increasing tryptophan concentrations, as well as modulating serotonin (5-HT) and dopamine (DA) turnover in regions implicated in depressive and anxiety disorders.  Another study investigated the effects of a milk drink containing Lactobacillus casei compared to a placebo.

In this study published by Benton et al. (2007), a total of 132 healthy older adults (average age of 61.8 years) were recruited.  A total of 124 adults completed the trail which involved drinking either a probiotic-containing (Lactobacillus casei Shirota) milk or a placebo milk devoid of bacterial cultures – for 20 days.  Results from the study demonstrated significant improvement in mood among a subset of those receiving the Lactobacillus casei Shirota (LcS) milk.

Researchers noted that Lactobacillus casei Shirota (LcS) cultures appeared to improve mood among those only with a low/depressive mood at baseline.  This suggests that Lactobacillus casei Shirota (LcS) may improve mood among those with subclinical depression, but may not further enhance mood among those with an already-good mood.  It is plausible that those with an already-good mood may already have adequate Lactobacillus casei Shirota (LcS) within their gut, whereas those with poorer moods may have had less Lactobacillus casei Shirota (LcS) and ultimately benefitted.

Studies of Lactobacillus casei Shirota (LcS) indicate that it may be more effective for anxiety than depression, but still could improve day-to-day mood after 20 days of administration.  Whether it’s an effective intervention for cases of severe anxiety and depression is unclear.  However, it should be hypothesized that Lactobacillus casei Shirota (LcS) may serve as an effective adjunct for those who fail to attain sufficient benefit from first-line treatments.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19338686/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17151594
  1. Bifidobacterium Infantis

Technically, Bifidobacterium infantis is a subspecies of Bifidobacterium longum, hence the reason most experts simply refer to it as Bifidobacterium longum.  However, scientific reports have documented therapeutic effects of this particular subspecies and have actually tested it against parent species Bifidobacterium longum.  The Bifidobacterium infantis strain is known for facilitating the production of acetic acid, lactic acid, and formic acid.

A study published by Desbonnet et al. (2008) investigated the antidepressant properties of Bifidobacterium infantis on Sprague-Dawley rats.  They noted that lack of beneficial gut bacteria may alter monoaminergic activity, alter the HPA (hypothalamic-pituitary-adrenal axis), and lead to onset of depression.  To determine efficacy of Bifidobacterium infantis as an antidepressant, they chronically administered it to the rats for 14 days while simultaneously assessed monoaminergic activity, neuroendocrine responses, and immune function.

Results indicated that Bifidobacterium infantis has zero effect on swim behaviors of the rats, but it attenuated detrimental biomarkers such as TNF-alpha, IL-6 cytokines, and IFN-gamma.  It also significantly bolstered concentrations of tryptophan (the amino acid precursor to serotonin), as well as kynurenic acid (a metabolic byproduct of tryptophan).  This suggests that Bifidobacterium infantis may increase serotonin production and/or concentrations.

Of additional interest to researchers was the fact that Bifidobacterium infantis decreased 5-HIAA (serotonin metabolites) in the prefrontal cortex and decreased DOPAC (dopamine metabolites) in the amygdaloid cortex.  Researchers concluded that Bifidobacterium infantis may promote antidepressant effects as a result of monoamine (serotonin and dopamine) modulation, as well as its anti-inflammatory effect.  That said, the study was unable to conclude whether this strain of probiotics legitimately improves mood.

Fortunately, a follow-up study was published in 2010 by the same researcher Desbonnet et al. to investigate the effect of Bifidobacterium infantis administration on mood.  For this study, researchers used a rat maternal separation (MS) model that is thought to accurately portray a combination of stress-related mood and gastrointestinal disorders.  The maternally-separated rats were administered either Bifidobacterium infantis OR Celexa.

Thereafter, they engaged in a forced swim test (FST) to determine their level of motivation.  Researchers collected measures such as: cytokine levels, central monoamine concentrations, and activation of the HPA (hypothalamic-pituitary-adrenal axis).  The maternal separation decreased swim behaviors and increased likelihood of immobility on the forced swim test (FST).

It also decreased levels of norepinephrine in the brain, stimulated release of peripheral IL-6 (interleukin), and increased amygdala corticotrophin-releasing factor (a neuropeptide implicated in stress responses).  Administration of Bifidobacterium infantis reversed behavioral abnormalities (e.g. swim behaviors and FST immobility), restored concentrations of norepinephrine in the brain, and attenuated immune dysfunction associated with the maternal separation.  Researchers concluded that Bifidobacterium infantis is capable of significantly altering neural function.

Although Bifidobacterium infantis hasn’t been tested in humans, preliminary evidence suggests that it may improve immune function, reduce inflammation, and combat neural changes associated with stress.  Its parent species Bifidobacterium longum is already known to possess antidepressant and anxiolytic properties.  Those experiencing stress-related depression may benefit from administration of Bifidobacterium infantis.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18456279
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20696216
  1. Bifidobacterium Breve

Bifidobacterium breve is non-motile, anaerobic, and rod-shaped with a cactus-like appearance.  It is thought to prevent the growth of candida albicans, an opportunistic fungus that is associated with the onset of oral and genital yeast infections and simultaneously inhibits the proliferation of disconcerting bacteria such as E. coli.  Its inclination to compete with other potentially harmful bacteria makes Bifidobacterium breve relatively unique in its mechanism of action.

Research has linked sufficient Bifidobacterium breve in the gut to healthy digestive function.  Those with depleted Bifidobacterium breve are more likely to develop allergies, diarrhea, flatulence, and even irritable bowel syndrome (IBS).  A study published in 2004 by Li et al. discovered that supplementation with Bifidobacterium breve improves intestinal health among low birth weight infants.

Lack of Bifidobacterium breve supplementation results in abnormal gut flora development, which may yield numerous deleterious health consequences – potentially for the entire lifetime of the infant.  In any regard, Bifidobacterium breve may also provide benefit to individuals with neuropsychiatric anxiety disorders.  A study conducted by Savignac et al. (2014) documented the effects of Bifidobacterium breve 1205 (a specific strain) to the antidepressant Celexa, as well as another Bifidobacterium strain, and a vehicle (control) treatment.

In the results, it was noted that Bifidobacterium breve 1205 was the only intervention that reduced anxiety in the elevated plus maze.  A follow-up study published by the same researcher Savignac et al. (2015) documented the effect of Bifidobacterium breve 1205 administration in anxious mice over an 11-week term.  It was compared to a vehicle intervention (control) and another Bifidobacterium strain.

Results indicated that the anxious mice receiving the Bifidobacterium breve 1205 strain were able to discriminate faster than the control group in an object recognition test.  This indicates that Bifidobacterium breve 1205 may enhance cognitive function among those with anxiety and possibly even those without.  Although Bifidobacterium breve may not be as effective as Bifidobacterium longum for alleviation of anxiety and depression, clinical evaluation in humans with anxiety is warranted.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26445348
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15491374
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25251188
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25794930
  1. Lactobacillus Acidophilus

Lactobacillus acidophilus a Gram-positive, microaerophilic bacterium that is perhaps the most popular of all bacteria in probiotic formulations.  Lactobacillus acidophilus is found within the gastrointestinal tract and oral mucosa of humans and certain strains are understood to elicit probiotic effects.  There is significant evidence to support the administration of Lactobacillus acidophilus for the treatment of diarrhea, SIBO (small-intestinal bacterial overgrowth), and vaginal infections.

It is also thought to improve immune function, inhibit growth of cancer cells, and reduce inflammation.  A study conducted by Rousseaux et al. (2007) assessed the effect of Lactobacillus acidophilus on the gut of animal models.  This study documented that a specific strain of Lactobacillus acidophilus known as “NCFM” upregulated peripheral mu-opioid receptors and cannabinoid receptors in epithelial cells within the intestine.

Whether this correlated to mood improvements and/or anxiety reductions is unknown.  However, research shows that animal models who overexpress the CB2 receptor are resistant to symptoms of depression.  Hypothetically, it could be that Lactobacillus acidophilus upregulates peripheral (and possibly central) CB2 receptors and, as a result, improves mood.

It is unclear as to how modulation of peripheral (or central) mu-opioid receptor densities affects mood of humans.  Assuming the combined cannabinoid and mu-opioid receptor modulation that occurs following administration of Lactobacillus acidophilus NCFM in mice is similar in humans, it may decrease depression, anxiety, and/or pain.  That said, the mood enhancing properties of specific Lactobacillus acidophilus strains warrant investigation.

A study published by Campana et al. (2012) highlighted the fact that Lactobacillus acidophilus is capable of blunting the growth of the pathogenic Campylobacter jejuni bacteria.  Campylobacter jejuni is capable of causing anxiety in mice and is associated with unfavorable gut health in humans.  The strain of Lactobacillus acidophilus known as “ATCC 4356” significantly decreased growth of Campylobacter jejuni and displaced its adhesion to cells.

It could be hypothesized that among those with abnormally high concentrations of Campylobacter jejuni, an anxiolytic benefit may be attained following administration of specific Lactobacillus acidophilus strains.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17159985/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20649579
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22271268/
  1. Trans-Galactooligosaccharides (TOS)

Transgalactooligosaccharide is a prebiotic of the galacto-oligosaccharides (GOS) family generated through enzymatic conversion of lactose.  It is a non-digestible food ingredient, that when administered, is thought to stimulate the growth of health-conducive bacteria within the body.  Galacto-oligosaccharides are unique in that they contain glycosidic bonds, allowing them to remain unhydrolyzed throughout the salivary and digestive tract.

As transgalactooligosaccharides (TOS) make their way through the intestinal tract, they promote growth of therapeutic bacteria such as Bifidobacteria and Lactobacilli.  Some also speculate that they may interfere with the growth of deleterious bacteria, thereby enhancing immune function, increasing nutrient absorption, and augmenting vitamin synthesis.  A study published in 2009 by Silk et al., specifically investigated the effect of transgalactooligosaccharides among individuals with IBS.

Researchers speculated that supplementation of transgalactooligosaccharides would improve colonic health of those with IBS compared to a placebo.  They organized a crossover trial with 44 patients diagnosed with Rome II positive IBS over a duration of 12-weeks.  All participants were divided at random to receive either: 3.5 grams per day of a prebiotic (transgalactooligosaccharides), 7 grams per day of a prebiotic (transgalactooligosaccharides), or 7 grams per day of a placebo formulation.

Symptoms of IBS were evaluated on a weekly basis with the 7-point Likert scale, while alterations in fecal microorganism content were monitored with the Bristol stool scale.  In addition, patient’s anxiety, depression, and quality of life were also evaluated.  Results indicated that the transgalactooligosaccharides prebiotic dramatically elevated bifidobacteria within fecal samples – regardless of the dose.

The lower dose prebiotic (transgalactooligosaccharides) at 3.5 grams per day improved stool consistency, flatulence, bloating, and all IBS symptoms.  That said, the higher dose at 7 grams per day significantly improved anxiety scores.  This suggests that a high-dose prebiotic at 7 grams per day in the form of transgalactooligosaccharides may be useful for the treatment of anxiety disorders, especially among those with IBS.

Note: The agent tentatively known as “B-GOS” or Bimuno-R is a form of a Trans-Galactooligosaccharide (TOS) in clinical trials for the treatment of anxiety.  I included it in the article “5 New Anxiety Medications in Development (2015).”  Keep in mind that this isn’t a “probiotic,” rather a prebiotic designed to stimulate the production of good bacteria in the gut.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19053980

Could a multispecies probiotic improve depression and anxiety?

There’s evidence from a study published by Steenbergen et al. (2015) suggesting that a multispecies probiotic with several of the aforementioned healthy bacterium may improve depressive symptoms.  This study tested a multispecies probiotic consisting of Bifidobacterium and Lactobacillus strains for a duration of 4 weeks.  The medley of bacterial species (and their specific strains) utilized in the study are listed below.

  • Bifidobacterium bifidum W23
  • Bifidobacterium lactis W52
  • Lactobacillus acidophilus W37
  • Lactobacillus brevis W63
  • Lactobacillus casei W56
  • Lactobacillus salivarius W24
  • Lactococcus lactis (W19 and W58)

The researchers specifically tested the effects of the multispecies probiotic on cognitive reactivity to sad mood.  Cognitive reactivity (CR) refers to dysfunctional attitudes as induced by a particular mood; in this study, the CR was determined in response to a sad mood.  Individuals with depression tend to exhibit abnormally high cognitive reactivity to mood changes, as well as detrimental changes in gut bacteria.

Researchers hypothesized that introducing a multi-strain probiotic formulation may reduce cognitive reactivity and thus ameliorate depressive symptoms.  For the study, researchers implemented a triple-blind, placebo-controlled, randomized design.  Participants were administered either a placebo OR the probiotic medley comprised of Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) – for a duration of 4 weeks.

To test the efficacy of the probiotic intervention, researchers assessed participants with the Leiden Index of Depression Sensitivity to document cognitive reactivity to sadness.  Results indicated that participants receiving the probiotic exhibited less cognitive reactivity to sadness compared to the placebo controls.  Decreased cognitive reactivity is associated with less aggressivity, rumination, and negative thoughts – associated with sadness.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25862297

Researchers Ait-Belgnaoui et al. (2014) documented the effect of a probiotic formulation marketed as the “Probio’Stick” on mice exposed to stress.  The Probio’Stick formulation consisted of the strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175.  The mice were exposed to either a water avoidance stress (WAS) task or a sham and stress responses were recorded by assessing ANS, HPA, peripheral neurotransmitters, and various neural biomarkers.

Results indicates that pretreatment with the Probio’Stick formulation prevented HPA axis and ANS alterations in the water avoidance stress (WAS) task.  What’s more is that this combination seemed to inhibit decreases in hippocampal neurogenesis and epigenetic modulation associated with stress.  This provides evidence that a combination product is capable of preventing neural changes associated with stress, thereby yielding either an anxiolytic effect OR an anti-anxiogenic effect.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24372793

An earlier study by Tillisch et al. (2013) attempted to determine how modification of the intestinal microbiota affects brain connectivity and responses to emotional attention tasks.  The study recruited 36 healthy women with no history of gastrointestinal nor psychiatric diagnoses.  The women were divided into three groups and set to receive the following: fermented milk product with probiotic (12 women), non-fermented milk product (11 women), and no intervention (13 women) – twice per day (b.i.d.) for a duration of 4 weeks.

The fermented milk product with probiotic (FMPP) contained the following:

  • Bifidobacterium infantis
  • Streptococcus thermophiles
  • Lactobacillus bulgaricus
  • Lactococcus lactis

Following the intervention, participants’ brain activity was recorded with fMRI neuroimaging during an emotional face attention task and at rest.  Ingestion of FMPP altered connectivity in the midbrain and neural activation.  Authors of the study concluded that intake of FMPP for 4-weeks can alter emotional and sensory processing functions in women – possibly enhancing mood and/or reducing anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23474283

Gut Bacteria that May Cause Anxiety and Depression

There are some bacteria that may contribute to the pathophysiology of anxiety and depression.  Most probiotic supplement companies would never include such bacteria in their product, so you shouldn’t have to worry.  A benefit associated with taking the right probiotic is that it may compete with and/or inhibit proliferation of these unhealthy gut bacteria, ultimately improving mood and reducing anxiety.

Citrobacter rodentium: This is a Gram-negative bacterium that is associated with higher mortality rates in mice.  Whether Citrobacter rodentium is detrimental to the health of humans and/or pathogenic remains unclear.  In mice, it is associated with increased rates of gastrointestinal disease and may facilitate an upregulation in other pathogenic bacteria within the intestinal lining.

A study published in 2011 discovered that Citrobacter rodentium was implicated in stress-induced memory dysfunction in mice.  Probiotic treatment successfully reversed the influx of Citrobacter rodentium within the gastrointestinal tract of mice, thereby attenuating the memory deficits.  That said, it is unlikely that Citrobacter rodentium solely causes memory deficits – it may also directly increase anxiety in mice.

A study from 2006 found that when mice were infected with Citrobacter rodentium, early-stages of the infection were associated with anxiogenic behavior.  This increase in anxiety was evidenced by behaviors exhibited on a hole-board open field apparatus by the mice that were administered this particular bacterium compared to the control group.  Researchers noted that the Citrobacter rodentium did not appear to increase inflammation, rather, it modulated vagal sensory neurons in such a way that the mice became anxious.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20966022/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16887154/

Campylobacter jejuni: This is a Gram-negative, non-spore, microaerophilic bacterium that is found within animals.  It is considered pathogenic in that it is associated with onset of gastroenteritis (the stomach flu), as well as food poisoning.  Those with elevated concentrations of Campylobacter jejuni tend to experience stomach aches, diarrhea, fever, and feel sick.

Research published by Lyte et al. (1998) documented the effects of Campylobacter jejuni infection in mice.  The researchers specifically infected the mice with a low amount of this bacterium and measured immune responses.  No immune activation was recorded as the level of Campylobacter jejuni wasn’t high enough to warrant a response.

However, even in the absence of immune activation, the mice became increasingly anxious.  The anxiety in mice was evidenced by behaviors in an elevated plus maze compared to controls.  This study portrays that, even at low levels, Campylobacter jejuni may alter neural processes that increase anxiety.  It should be speculated that elevations in Campylobacter jejuni among humans may induce anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9811366/

Clostridium: There’s evidence linking abnormally high (10-fold) Clostridium concentrations in the gut of children with autism compared to individuals without autism.  Autism is associated with an array of deleterious neurophysiological consequences, including anxiety and depression.  Administration of Lactobacillus strains are known to displace Clostridium, potentially a direct way by which strains of Lactobacillus may improve mood.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25468489

Enterococcus faecalis: This is a Gram-positive bacterium commonly found in the GI tract of humans.  It is considered pathogenic in that it can cause urinary tract infections, meningitis, and heart damage.  Unfortunately, this particular species is very resistant to antibiotics and can survive for extended durations without any nutrients.

Research suggests that it produces a significant amount of D-lactic acid from within the gut, which likely compromises brain function.  Individuals with chronic fatigue syndrome tend to have abnormally high concentrations of Enterococcus faecalis within the gut lining.  Eliminating accumulation of this bacterium from the gut is likely to improve health.

Streptococcus sanguinis: This bacterium is Gram-positive, anaerobic, and a normal inhabitant of the human mouth.  It is abundant in the formation of dental plaque and is actually thought to protect the teeth from cavity formation.  However, you don’t want this particular bacterium to enter your bloodstream, nor your gut.

When this bacterium leaches into the bloodstream, it may colonize within your heart valves and damage them.  If it works its way down to your gut, it may also stimulate the production of D-lactic acid, a well-known neurotoxin.  Studies have shown that people with chronic fatigue syndrome tend to have more of Streptococcus sanguinis within their guts than those without.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25402818

Microbiota implicated among those with major depression…

A study published by Jiang et al. (2015) investigated the microbiota implicated among individuals that had been diagnosed with major depressive disorder (MDD).  They specifically assessed the fecal matter of 46 individuals with major depression and compared it to 30 healthy controls.  Among the depressed individuals, increases in the concentrations of the following phyla (a higher order classification) were apparent:

  • Actinobacteria
  • Bacteroidetes – Specifically it was found bacteria within the genus Alistipes were higher among those with depression than healthy controls.
  • Enterobacteriaceae
  • Proteobacteria

Interestingly, there was an inverse correlation between Firmicutes in the stool and depression.  Those with greater concentrations of Firmicutes were less likely to be depressed.  An earlier study by Naseribafrouei et al. (2014) documented a plethora of Bacteroidales in the stool of those with depression, whereas the quantity of Lachnospiraceae was considered insufficient – compared to healthy individuals.  It seems as though when these strains are overpopulated relative to healthy strains, mood disorders may be more likely to occur.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20664638/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24888394/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25882912

How Probiotics May Treat Depression & Anxiety

To many individuals, it may be unclear as to how taking a probiotic supplement or getting healthy microorganisms in their gut may improve mood and reduce anxiety.  In recent years, research has shed light on the fact that the gut sends signals to the brain in numerous ways.  In effort to accurately describe the communication between the gut and brain, researchers have coined the term Gut-Brain-Axis, sometimes abbreviated under the acronym “GBA.”

Keep in mind that the relationship between the gut and the brain is bidirectional, implying that the brain influences the gut and gut influences the brain.  This means that if you’re psychologically stressed, the brain will alter the bacteria content within your gut.  On the other hand, depleting healthy bacteria from your gut (such as while taking antibiotics) may significantly alter neurochemical processes within the brain, thereby changing your mood.

For the purposes of this article, we are focusing specifically on how gut bacteria (such as in the form of probiotics) likely influences brain function.  When gut bacteria changes, it modulates activity in the ENS (enteric nervous system), a complex peripheral network with over 500 million neurons – often dubbed the “second brain.”  Gut bacteria also influences both branches of the ANS (autonomic nervous system), namely the sympathetic and parasympathetic.

ENS: The ENS is comprised of afferent neurons, motor neurons, and glial cells.  The microorganisms in a person’s gut sends signals to these peripheral neurons, which in turn have implications for CNS function.  When a person’s gut bacteria are suboptimal or non-existent (such as in studies of “germ-free” mice), significant abnormalities are observed within the ENS such as: fewer ganglia and thinner nerve fibers.

  • Peripheral neurotransmitters: There are many neurotransmitters generated within your gut. The generation of these neurotransmitters is thought to be contingent upon the specific bacterial inhabitants.  Research has shown that gut bacteria are capable of producing: acetylcholine, GABA, histamine, norepinephrine, and serotonin.  For example, certain lactobacilli are capable of converting glutamate (an excitatory neurotransmitter) to GABA (an inhibitory neurotransmitter).  These peripheral neurotransmitters stimulate receptors in the gut that could affect mood.  It has also been hypothesized that a percentage of these neurotransmitters may work their way up to the brain and cross the blood-brain-barrier (BBB) – ultimately influencing neural activity.
  • Peripheral receptors: Not only can bacteria in your ENS stimulate the production of peripheral neurotransmitters, they can also alter receptor densities. Receptor modulation is evidenced within rodent studies and may have significant implications for those with chronic pain conditions.  One study documented the effect of a probiotic supplement on the peripheral receptors in animal models and found that cannabinoid and opioid receptor densities were upregulated.
  • Central neurotransmission: Strains of gut bacteria may also be able to directly alter neurotransmitter levels in the brain, regional turnover, and/or receptor densities. One study discovered that animals administered Lactobacillus rhamnosus JB-1 significantly altered the entire GABA (gamma-aminobutyric-acid) system within the brains of animal models, ultimately lowering their anxiety and depression.  It is unclear as to exactly how central neurotransmission is altered

Our bodies are an integrated system and there’s no getting around the fact that activity within the ENS (the “second brain”) also mediates signaling within the CNS.  Researchers highlight that peripheral ENS neurons can influence the vagus nerve, particularly vagal afferents (or those signaling to the CNS).  The fact that vagal afferents are influenced by ENS activity indicates that the ENS can affect brain function.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24997036

Vagus nerve: Most evidence indicates that the predominant modality by which gut bacteria influence brain activity is via afferent vagal nerves.  These vagal nerves send sensory signals outward from the vagus nerve to the CNS.  Studies in mice have shown that when the vagus nerve is removed (via a vagotomy), administration of healthy gut bacteria fail to reduce anxiety, stress, and/or improve mood.

  • Cerebral blood flow: It is widely documented that the vagus nerve is capable of influencing cerebral blood flow. Alterations in cerebral blood flow, especially to particular regions, are thought to influence someone’s psychological state and propensity to engage in certain behaviors. Among those with depression, vagus nerve stimulation decreases cerebral blood flow to some regions (e.g. orbitofrontal cortex), while increases it to others (e.g. medial putamen). Since gut bacteria mediate signaling from the vagus to the brain, there’s no doubt that they also affect cerebral blood flow on a regional basis.
  • Neurotransmission: Vagus nerve stimulation likely alters neurotransmission in the brain, but the exact neurotransmitters affected may be a direct reflection of signaling received from gut bacteria. There are some studies linking vagus nerve stimulation to changes in acetylcholine, but it is unclear as to if these occur in the CNS.  That said, it is likely that bacterial-induced changes to vagus signaling can affect concentrations of neurotransmitters in the synaptic cleft, thereby affecting neuronal signaling.
  • Neuroelectrical activity: We should also consider that bacterial-induced changes to vagal signaling may alter neuroelectrical activity in the brain. In other words, those taking probiotics may experience changes in their brain waves.  These brain wave changes may be in part a byproduct of other changes such as altered regional activation and neurotransmission.  However, it could be that neuroelectrical impact is an important component of neuromodulation associated with gut bacteria.
  • Regional activation: Studies have shown that administration of fermented foods and probiotics for several weeks can alter regional activity within the brain. In other words, certain regions become more or less active (e.g. hypothalamic-pituitary-adrenal axis) as a direct result of bacteria in the gut.  The exact neural activation and deactivation correlates associated with particular strains of probiotics aren’t fully understood.  However, the effects of bacteria upon regional activation are likely mediated (at least in part) via the vagus nerve.

However, mice with a vagus nerve and normative vagal function exhibit significantly less anxiety and mood improvements following administration of the same bacteria.  Vagus nerve dysfunction has been implicated in many psychiatric and general health conditions ranging from depression to obesity.  In fact, there are treatments with vagus nerve stimulators that have significantly improved mood and/or reduced obesity in certain users. (Read: VBLOC Therapy for Weight Loss).

It is apparent that microorganisms in a person’s gut increase or decrease the firing rate of vagal nerves.  This altered firing rate has potential to activate and/or deactivate neural pathways in the brain and mediate neurotransmission.  Though there are other ways in which gut bacteria alter function within the brain, none are as significant as via modulation of vagal tone.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23139216/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23759244
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22037127

Other ways probiotics (gut bacteria) may treat depression and anxiety…

There remains a myriad of ways by which probiotics and prebiotics may improve symptoms of depression and anxiety.  Administration of the right probiotics can reduce inflammation, lower Substance P, deliver neurotransmitters to the brain, alter hormone concentrations, and reduce HPA axis activity.  In addition, probiotics may repair intestinal barriers to improve nutrient absorption while simultaneously overtaking pathogenic bacteria – the culmination of which may directly increase well-being.

Anti-inflammatory: Individuals with depression, anxiety, and excess stress often have simultaneous inflammation.  Some experts believe that chronic, low level inflammation is implicated in the pathogenesis of many neuropsychiatric disorders.  Interestingly, some research highlights that taking anti-inflammatory agents for depression may be an effective treatment.

In many cases, inflammation is perpetuated and/or exacerbated by the presence of pathogenic bacteria in the gut.  This inflammation also facilitates increases in Substance P, a neurotransmitter associated with depression. Probiotics reduce pathogenic bacteria, decrease inflammation, lower Substance P – and ultimately could improve mood.

Antioxidant effect: There is evidence that administration of probiotics provides an antioxidant effect by scavenging free radicals and possibly inhibiting the production of reactive oxygen species (via pathogenic bacteria).  Individuals diagnosed with depression and anxiety tend to exhibit heightened oxidative stress which can cause neuroinflammation and lead to a host of abnormalities within the CNS.  Treatment with the right probiotics can reduce reactive oxygen species and improve neural function, and possibly a person’s neuropsychiatric condition.

Delivery of neurotransmitters: Probiotics are sometimes called “psychobiotics” because they are thought to directly modulate brain activity.  One way by which they modulate brain activity could be via the generation and/or delivery of neurotransmitters to the CNS.  It is understood that gut bacteria generate neurotransmitters within the peripheral nervous system, but it may be that they also deliver neurotransmitters such as GABA and serotonin to the brain.  Even if the effect of probiotics on the brain is indirect such as through the vagus nerve, spinal cord, and/or neuroendocrine systems, they appear to alter neurotransmission in the CNS.

Hormonal alterations: Gut bacteria not only affect the ENS, but also the entire autonomic nervous system including parasympathetic and sympathetic pathways.  It is hypothesized that gut bacteria may alter generation of hormones within the body, possibly by mediating autonomic tone.  An overactive sympathetic nervous system is associated with stimulation of the HPA axis, which stimulates release of CRF and ACTH – which in turn facilitates glucocorticoid release.

Ultimately when someone is highly stressed, anxious, and/or possibly depressed – they may have abnormally high cortisol.  Probiotics are thought to reduce activity within the HPA axis, which inhibits release of stress hormones and may facilitate relaxation and/or positive mood.

Intestinal barrier restoration: Some individuals with depression and/or anxiety may also experience leaky gut syndrome.  Leaky gut syndrome is classified as damage to the intestinal lining that allows toxins to “leak” through.  Leakage of unfiltered toxins can cause autoimmunity, neuroinflammation, and possibly even neurotoxicity (via circulating endotoxins).

Administration of probiotics has been shown to restore tight-junction integrity within the intestine, thereby correcting leaky gut.  A simple correction of leaky gut could have significant therapeutic implications for mental health and overall well-being.  It may also reduce flatulence and improve stool composition.

Monoamine oxidase inhibition: The enzyme monoamine oxidase is responsible for scavenging neurotransmitters between synapses.  Those with depression and anxiety often derive benefit from drugs that inhibit the activity of the monoamine oxidase enzyme.  Inhibition allows neurotransmitters to remain in the synaptic cleft for a longer duration, which facilitates improved neuronal communication.

Studies have shown that certain strains of gut bacteria (e.g. Bifidobacterium animalis 01) can also inhibit the activity of monoamine oxidase.  Assuming they inhibit monoamine oxidase to a moderate extent, it is logical to suspect an improved mood of the user, possibly with less anxiety.  Perhaps in the future a potent bacterial strain will be discovered that inhibits MAO to a significant enough extend to clinically treat depression.

Neurotoxicity inhibition: Those with a gut lining full of pathogenic bacteria may not realize that these bacteria are affecting their cognitive function and mood.  When pathogenic bacteria within the gut outnumber healthy bacteria, they may produce metabolites such as D-lactic acid and ammonia.  If you are struggling with depression, foggy thinking, and/or excess anxiety – there’s a chance that your gut may be generating toxins that work their way up to your brain.

These neurotoxins inflict damage to the brain by killing brain cells and inducing a state of neuroinflammation and neurochemical disarray.  Your neurons will have a tougher time signaling to each other, neurotransmitter levels will likely be altered, and mitochondria will literally become dysfunctional.  Introducing healthy bacteria in your gut should help kill off some of the bad bacteria and prevent D-lactic acid build-up from pathogens like Enterococcus faecalis and Streptococcus sanguinis.

Nutrient absorption: Some would argue that if your gut isn’t healthy and/or is leaky, you may not be absorbing enough nutrients from the foods that you eat.  Lack of nutrient absorption may detrimentally affect your mood and/or cognitive function.  Even if you are eating seemingly enough foods with the right nutrients, if you aren’t sufficiently absorbing them, the deficiency could influence the severity of your depression and/or anxiety.  Utilizing a probiotic can restore healthy bacteria within the gut to repair the lining and improve absorption, which thereafter, may reduce depression and/or anxiety.

Pathogenic bacteria reduction: Introducing bacteria that have been proven to be improve health outcomes can reduce pathogenic bacteria.  Many of the healthy bacteria compete with existing pathogenic bacteria for resources in your gut.  Regular administration of a probiotic will keep these pathogenic bacteria such as Clostridium difficile in-check.

Since these pathogenic bacteria can also detrimentally affect brain function, you may notice significant improvement in your mental health after probiotics.  For example, studies have shown that pathogenic bacteria compromise hippocampal neurogenesis, alter hypothalamic genes, and affect synaptic plasticity to facilitate a stress response.  Healthy gut bacteria appear to attenuate these unwanted neural alterations induced by pathogens.

Substance P reduction: Those with significant inflammation tend to have high levels of Substance P.  Additionally, studies have shown that among people diagnosed with major depression, Substance P production is upregulated.  Comparatively, those without depression tend to have lower Substance P concentrations.

Lacking healthy gut bacteria is also directly associated with high Substance P; animal models administered antimicrobials exhibit an upregulation.  Fortunately, administration of probiotics has been shown to downregulate Substance P – possibly by lowering inflammation.  In any regard, this may be one mechanism by which probiotics improve mood.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25834446
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23320049
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25822014
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18619532/

Probiotics for Depression & Anxiety (The Research)

There are numerous studies that have been conducted investigating the therapeutic efficacy of probiotics for the treatment of depression and anxiety.  While most research is limited to animal models, a few studies have shown promising results in humans.  Included below are some important scientific articles that you should read if you are interested.

Perhaps the most thorough explanation comes from a 3-part series written by Alison Bested et al. entitled “Intestinal microbiota, probiotics, and mental health.”  Part 1 eloquently summarizes the historical application of gut bacteria for the treatment of various medical conditions, Part 2 addresses how the gut influences physiology, and Part 3 discusses trials of bacteria for the treatment of neuropsychiatric conditions.  Below is a synopsis of the most relevant “Part 3,” as well as other informative research.

2015: Systematic review of evidence to support the theory of psychobiotics.

A systematic review of evidence conducted by Romijn and Rucklidge (2015) investigated the efficacy of “psychobiotics,” or using probiotics for the treatment of neuropsychiatric disorders.  Though many human and animal studies had been published documenting the effects of probiotics as interventions for neuropsychiatric conditions, no researchers had reviewed the literature.  Researchers collected studies dating through July 2014 from numerous sources including: Cochrane, Medline, and PubMed – to name a few.

The inclusion criteria for the systematic review was that the research needed to be: double-blind, randomized, placebo-controlled, and human trials.  In other words, no animal studies were used and only the most robustly designed human research was analyzed.  Furthermore, the included studies needed to gauge psychological outcomes and/or symptoms of psychiatric disorders following treatment of the probiotics compared to a placebo.

Researchers Romijn and Rucklidge each analyzed trials on an independent basis and evaluated the quality of the methods.  A total of 10 studies met inclusion criteria necessary to be included in the systematic review.  After extracting and synthesizing the data from these studies, the researchers concluded that there is “very limited evidence” to support the efficacy of probiotics for psychological outcomes.

It was concluded that more research is warranted before any inferences can be made regarding the clinical efficacy of probiotics for psychiatric conditions.  In other words, without more robustly-designed, larger-scale trials – it is difficult to know whether probiotics will prove efficacious for conditions like depression and anxiety.  However, it is important to avoid dismissing their efficacy altogether, as some evidence suggests that they may work.

There are numerous concerns that need to be addressed in regards to psychobiotics including: long-term effects, optimal CFUs, frequency of administration, and optimal strains necessary to treat a particular psychiatric condition.  As more data is generated in forthcoming years, we should get a better understanding of how various probiotic strains can influence the brain.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26370263

2015: The Gut-Brain Axis: The Missing Link in Depression.

Researchers Evrensel and Ceylan (2015) published an article entitled “The Gut-Brain Axis” and discussed how it may directly contribute to neuropsychiatric disorders such as major depression and anxiety.  They discussed the fact that the gut microbiota is linked to an array of conditions including: autism, diabetes, obesity, schizophrenia, and more.  Furthermore, it was mentioned that the latest neuroscience suggests that microbiota may contribute to brain development.

Microorganisms within the gut may also help deliver neurotransmitters such as 5-HT and GABA to the CNS.  Authors note that research from animal studies document a combination of antidepressant and anxiolytic properties of probiotics.  They believe that a mechanism by which probiotics may improve health is through modulation of neuroendocrine and immune function. This is a report worth reading if you’re interested in learning more about the impact of the gut on mental health.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26598580

2014: The gastrointestinal tract microbiome, probiotics, and mood.

A report by Vitetta et al. (2014) discussed the fact that many people with treatment-resistant depression fail to derive benefit from standardized pharmacological interventions.  They may try an SSRI, SNRI, TCA, MAOI, and atypical antidepressants with no relief.  They may mix and match various other adjuncts along with a first-line option and derive insufficient benefit – or may end up feeling worse.

In the small percentage of non-responders to traditional recommended pharmacology for depression, individuals need alternative treatments.  Though nutraceuticals such as Omega-3 fatty acids, St. John’s wort, SAMe, L-tryptophan, etc. – may prove helpful, they are clearly not a panacea.  Researchers suggest that microbiome alterations within the GI tract may hold potential to ameliorate mood disorders and serve as a viable adjunct to traditional psychopharmacology.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25266952

2014: Microbiota, immunoregulatory old friends and psychiatric disorders.

A report by Rook et al. (2014) referred to microorganisms in the gut as functioning via an “Old Friends” mechanism.  They use the “Old Friends” terminology to imply that throughout evolution, many of these gut bacteria co-evolved with humans.  These days, the living conditions and lifestyles exhibited by modern humans is much different than throughout a bulk of evolution.

The changes in diet, increases in antibiotic use, fewer infections, and heightened sanitization from birth – may have deleterious implications for gut health.  As a result, this may contribute to allergies, autoimmunity, and systemic inflammation – along with a host of interrelated neuropsychiatric disorders.  Researchers specifically note that certain microorganisms are associated with inflammation, which may paly an important role in the pathogenesis of conditions like depression and anxiety, as well as stress-resilience.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24997041

2014: Gut emotions – mechanisms of action of probiotics as novel therapeutic targets for depression and anxiety disorders.

A synopsis of literature regarding “gut emotions” and probiotics as treatments for depression and anxiety was conducted by Slyepchenko et al. (2014).  Researchers in this report mention that over the past 10 years, there’s been an increasing amount of evidence suggesting a symbiotic relationship between the microbiota within the gut and the brain.  The communication between the two takes place via stimulation from the ENS to the CNS and vice-versa.

The specific signaling pathways from the gut to brain and brain to gut are referred to as the “gut-brain-axis” (GBA).  Researchers believe that probiotics can alter signals sent from the ENS to CNS via the GBA, which may prove useful for the prevention and/or treatment of neuropsychiatric disorders.  They outline the fact that probiotics may alter neural, endocrine, and/or immune pathways to elicit their effect – making them novel therapeutic interventions for a myriad of conditions.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25470391

2014: The impact of microbiota on brain and behavior: mechanisms & therapeutic potential.

Another study published in 2014 by Borre et al. noted that microorganisms within the body are necessary to maintain homeostatic neurophysiology.  When gut bacteria are altered significantly, the host’s mood, cognition, and behavior may change.  Like other researchers, they note that there’s a bidirectional relationship between microorganisms within the gut and psychological states; changes to either affects the other.

Those with neurodevelopmental disorders (e.g. autism) and stress-related disorders tend to exhibit bacterial dysbiosis within the gut.  The colonization of important bacteria within the gut is necessary to facilitate CNS development, immune function, and endocrine function.  These researchers believe that the gut communicates with the brain through neural, hormonal, immune, and metabolic pathways.

They also mention that alterations of microorganism concentrations in the gut may be helpful for the treatment of CNS disorders.  If you’re interested in learning more about the therapeutic potential of probiotics as treatments for neuropsychiatric disorders, consider reading the full text of this article.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24997043

2013: Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III – convergence toward clinical trials.

A comprehensive report published in 2013 by Bested et al. documented the relationship between intestinal microbiota and mental health.  Researchers documented the fact that pathogenic dysbiosis within the gut was linked to increased activation within the amygdala and other subregions within the limbic system.  Cases of pathogenic dysbiosis are associated with increased vagal tone or activation of the vagus nerve.

The gut bacteria appear to utilize the vagus nerve as a chief conduit to mediate neural activity.  Researchers mentioned that in animal studies, administration of probiotic strain Bifidobacterium longum (NCC3001) reduces anxiety among animals with a healthy vagus nerve, but is unable to reduce anxiety among animals without a vagus nerve.  Researchers believe that the vagus nerve has potential to either induce anxiogenic or anxiolytic effects depending on signaling received from gut bacteria.

They documented that administration of Lactobacillus rhamnosus strains were able to attenuate anxiety and depression in animal models.  It appeared as though this strain modulated the neurotransmission of GABA (gamma-aminobutyric acid), thereby facilitating a calming effect.  However, this effect was contingent upon functioning of the vagus nerve – mice without a vagus nerve experienced no favorable anxiolytic effect.

The extent to which the neurotransmission of GABA is modified as a result of gut bacteria isn’t fully elucidated.  That said, oral intake of GABA derived from fermentation of Lactobacillus hilgardii has been proven to reduce anxiety.  Additionally, administration of Bifidobacterium longum reversed hippocampal BDNF abnormalities induced by the parasite Trichuris muris.

Authors of the report highlight the fact that antibiotics have been successfully used as a treatment for depression.  Although most wouldn’t consider antibiotics a feasible treatment for mood disorders, minocycline has demonstrated clinically significant antidepressant properties.  Additionally, it should be noted that neuropsychiatric disorders such as major depression are linked to suboptimal expression of the biomarker MMP-9 (matrix metalloproteinase 9).

MMP-9 is also associated with substantial loss of important intestinal microorganisms and poor microorganism diversity within the gut flora.  Interestingly, adherents to the Mediterranean diet exhibit decreased MMP-9 activation whereas ingestion of a multi-strain probiotic is associated with enhanced MMP-9 and decreased oxidative stress.  Therefore, it is clear that the relationship between gut flora, biomarkers, and neurophysiological health outcomes is highly complex.

Researchers note that quantities of specific strains of gut bacteria influence neurotransmission in the brain.  When there’s an imbalance of gut bacteria such as overpopulation or underpopulation of a certain strain, the host engages in different behaviors.  Animal models show that germ-free animals differ significantly from those with standardized microbiota – contributing to alterations in appetite, anxiety, sedation, and serotonin production in the brain.

The bacterial strain Lactobacillus plantarum C29 has been shown to increase BDNF (brain derived neurotrophic factor) when isolated from kimchi.  Low levels of BDNF are associated with depression, anxiety, and other adverse health conditions.  Administration of Lactobacillus plantarum C29 appears to directly improve behavior among animal models with depression.

What’s more, when an animal’s diet is strategically modified with the intention of increasing lactobacillus quantities by 2-fold, anxiety behaviors significantly decrease.  A common strain of probiotic, lactobacillus acidophilus has demonstrated significant efficacy in reducing chronic fatigue symptoms in animal models.  Biomarker measures of oxidative stress and inflammation (via inflammatory cytokine TNF-alpha) appear reduced among those receiving the lactobacillus acidophilus strain.

Researchers speculate that the strain “Bifidobacterium animalis 01” may reduce oxidative stress and enzymatic activity of monoamine oxidase.  The combination of reduced oxidative stress and less MAO activity allows for heightened concentrations of important neurotransmitters within the synaptic cleft – which improves communication between neurons.  These bacteria also may alter concentrations of the neuropeptide Substance P.

When gut microbes are deliberately modified via laboratory experiments, most animals exhibit upregulation of Substance P.  An upregulation in Substance P is associated with anxiety behaviors, depression, and aggression.  Researchers point out the fact that responders to antidepressants tend to exhibit noticeable reductions in Substance P.

In other words, Substance P concentrations are inversely correlated with favorable mood; the lower the Substance P, the better one’s mood.  This finding is also supported with research of cannabinoid (CB)-2 receptor agonists, noting that they reduce anxiety and depression – possibly [in part] by decreasing Substance P.  Bringing things full circle, researchers highlight the preliminary evidence that probiotics may upregulate CB2 density.

They also noted that neuroimaging studies (with fMRI) measured changes in brain activation as a result of probiotic administration.  A double-blind, placebo-controlled study with 45 healthy female volunteers showed that administration of a probiotic medley (Bifidobacterium lactis CNCM I-2494, L. bulgaricus and L. lactis) in the form of yogurt for a full month altered activation of the mid- and posterior-insula.  The reduction in activity within the mid/posterior insula was associated with decreased emotional reactivity when exposed to a negative stimulus.

Near the end of their publication, researchers discussed “direct clinical investigations” of probiotics.  They noted one study in which supplementation of Lactobacillus casei improved mood among 132 healthy adults compared to a placebo.  A smaller pilot study tested the effect of Lactobacillus casei on 39 patients with chronic fatigue syndrome compared to a placebo and anxiety scores (as measured by the Beck Anxiety Inventory) were substantially lower among those receiving the probiotics.

Other research has shown that the combined administration of Lactobacillus helveticus and Bifidobacterium longum for a full month improved neuropsychiatric states of anger, anxiety, and depression – compared to a placebo.  Hormonal biomarkers were altered as a result of the concurrent Lactobacillus helveticus with Bifidobacterium longum administration, leading to noticeable reductions in cortisol.  Trials of the prebiotic fiber “trans-galactooligosaccharide” among those with IBS increased concentrations of bifidobacteria and substantially attenuated anxiety symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23497650

2013: Melancholic microbes: a link between gut microbiota and depression?

A report by Dinan and Cryan conferred the increasing popularity of gut-brain research.  They highlighted the potential of microbiota to alter brain function and facilitate health or perpetuate diseased states.   Effects of various interventions such as antibiotics, probiotics, and fecal microorganism transplants – have been documented as potentially impacting the brain.

In addition, studies have investigated deliberate bacterial GI infections as well as animals devoid of all gut bacteria.  Regardless of the intervention and/or modality of altering gut function, brain chemistry and behaviors were influenced as a result.  Researchers speculate that development of psychobiotics for psychiatric disorders may be beneficial, especially for individuals with neruogastroenterological disorders (e.g. IBS).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23910373

2005: Major depressive disorder: probiotics may be an adjuvant therapy.

A report published by Logan and Katzman (2005) suggested that probiotics may be an effective antidepressant augmentation strategy.  Pairing the right strains of healthy bacteria with a pharmacologically-proven antidepressant may be more effective than a standalone antidepressant (or probiotic).  Researchers particularly highlighted the fact that nutrition has a significant impact on mood and is often overlooked among those with neuropsychiatric disorders.

Those with depression tend to have nutrient deficiencies, inflammation, oxidative stress, impaired GI function, and decreased omega-3 fatty acids.  Researchers note that SIBO (small-intestinal bacterial overgrowth) can impair nutrient absorption, and when coupled with stress, pathogenic microorganisms may proliferate – overtaking Lactobacilli and Bifidobacterium species.  Fortunately, probiotics can decrease inflammation, reduce oxidative stress, reverse SIBO, and ameliorate nutritional deficiencies.

Authors of this publication speculate that probiotics administration may enhance production of BDNF (brain-derived neurotrophic factor) – a biomarker that is often reduced among those with depression.  BDNF is directly linked to hippocampal neurogenesis or growth of new brain cells, which in turn is associated with an antidepressant response.  Though there aren’t any known trials of probiotics paired with antidepressants (as of yet), they may be an effective adjunct – for both general and mental health.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15617861

5 Recommended Probiotics for Depression and Anxiety

Below is a list of several probiotics on the market that may help depression and anxiety.  When looking for a probiotic supplement, you may want to consider a few things including: the specific bacterial strains within the product, legitimate customer reviews, and CFU (colony forming units).  Since we don’t have the equipment to verify the survival rate of the bacteria ingested via a probiotic, it helps to look for honest reviews of the product that suggest it actually works.

If you’re endeavoring to treat symptoms of depression and/or anxiety, you’ll want to look for specific strains that were highlighted above.  There are many multispecies probiotics on the market that are engineered to populate the gut with a diverse amount of healthy bacteria.  These probiotics may contain between 5 and 20 distinct bacterial species.

On the other hand, various probiotic products may include just a single species (e.g. Lactobacillus acidophilus) or a dual-species with 2.  When it comes to probiotics as interventions for mental health, more species may not provide greater benefits.  It is up to you to experiment and find whether a specific probiotic product is better for your individual neurophysiology than another.

  1. Hyperbiotics PRO-15

A probiotic that I personally take is Hyperbiotics PRO-15.  It is the first one that I’ve taken and one that I’ve stuck with.  I’m not sure how it compares to other products out, but it clearly is a juggernaut on Amazon and the users seem to like it.  Furthermore, it contains 15 (healthy) probiotic strains coupled with a healthy prebiotic.

Upon hearing some experts discuss probiotics, some have mentioned the fact that they aren’t sure whether certain supplements actually deliver the bacteria to the gut.  Many products contain the right bacteria, but the formulation is unknowingly flawed and the bacteria included within the product “die-off” long long before making it to the gut.  As a result, people are forking over cash for products that aren’t having any impact on gut health.

Hyperbiotics PRO-15 implements a patented technology called BIO-tract which forms a gel matrix to protect microorganisms from getting killed by stomach acids prior to reaching the intestinal tract.        In addition, rather than simply unleashing all of the microorganisms at once, the BIO-tract technology facilitates a controlled-release, allowing for consistent release of the microorganisms from the probiotic pearls throughout the day.  Moreover, each pearl contains 5 billion colony forming units (CFUs) which (according to the company) is equivalent to 75 billion CFUs of standard probiotics.

PRO-15 ingredients…

The bacteria included in PRO-15 supplements is diverse.  If your goal is diversity for optimal gut and brain health, this supplement may be a good starting point.  From the above list of 10 best gut bacteria for depression and anxiety, you’ll see that many bacteria from that list are included in this product.  Examples include: B. longum, L. rhamnosus, L. plantarum, B. infantis, B. breve, L. acidophilus, and L. casei.

  • Plantarum
  • Fermentum
  • Acidophilus
  • Infantis
  • Casei
  • Longum
  • Rhamnosus
  • Lactis
  • Reuteri
  • Salivarius
  • Paracasei
  • Gasseri
  • Bifidum
  • Breve
  • Thermophilus

It should be noted that the Lactobacillus casei studied in research was the “Shirota” subspecies.  Since this particular supplement doesn’t specifically state L. casei Shirota (LcS) – it may not be the type necessary to improve mental health.  That said, it contains 7 of the species that have been researched for depression and anxiety.  It also contains a potentially useful prebiotic in the form of FOS (fructooligosaccharides).

  1. Earth Pearl Probiotics

Another seemingly quality brand is Earth Pearl Probiotics.  This product is non-GMO, lactose free, and packages the probiotics in the form of a pearl.  Just like the PRO-15 product, the “pearl” formulation is capable of protecting the probiotics from stomach acids that may kill them before they are able to reach the intestine.  This protective pearl is marketed at being 15-fold more effective than encapsulated probiotics in term of the quantity of bacteria that reach the intestinal wall.

This may be due to the fact that the “pearls” have been engineered in such a way as to create a barrier between stomach acids and the bacteria.  Other products such as those in veggie capsules may be less effective (in terms of how much bacteria are delivered to the intestine).  Based on the delivery method and numerous positive testimonials, Earth Pearl seems to have a good product.

Earth Pearl Probiotics ingredients…

Unlike the PRO-15 product, Earth Pearl contains just 5 species of bacteria, marketed as “power strains.”  Essentially this is a similar product to PRO-15, but instead of 15 strains, you’re just getting 5.  Not everyone may like all of the strains included within the PRO-15 product and may want to test out something that provides a little diversity, without over diversification.

  • Acidophilus
  • Plantarum
  • Reuteri
  • Infantis
  • Lactis

In addition to the 5 healthy probiotics, the Earth Pearl product contains FOS (Fructooligosaccharides) prebiotic.  Overall, anyone looking for a quality product with a few less strains than the PRO-15 product should consider Earth Pearl.  Certainly a quality probiotic to test if you’re having difficulty choosing which one to buy.

  1. NOW Foods Probiotic-10

A supplement company that creates pretty good products for low prices is NOW Foods.  Most of their products have been critically reviewed by customers and independent reviewers.  Their probiotic is a hot seller because it is slightly cheaper than others, yet provides diversity in the number of strains included.

My only problem with this product is that I’m unsure as to how effective the vegetarian capsule is at shielding the probiotics from stomach acids after ingestion.  I don’t doubt that some of the bacteria survives and proliferates within the intestinal lining, but I’m suspecting that a fair amount may die off as a result of the veggie capsule delivery.

NOW Foods probiotic ingredients…

The product contains 25 billion CFU (colony forming units) per serving, which is a fair amount.  It contains slightly fewer strains than the PRO-15 product, whereas it contains double that of the Earth Pearl product.  In addition to the species listed below, the product also contains FOS (Fructooligosaccharides) to stimulate growth of healthy bacteria in the gut.

  • Acidophilus
  • Plantarum
  • Rhamnosus
  • Paracasei
  • Salivarius
  • Lactis
  • Longum
  • Breve
  • Casei

As you can see, the NOW Foods probiotic product contains many beneficial bacteria to populate the gut.  The strains such as L. plantarum, L. rhamnosus, B. longum, B. breve, L. casei, and L. acidophilus may be conducive to mental health.  And although unlisted above, NOW’s product includes the exact strain type which is helpful for identification purposes.

  1. Jarrow Formulas Ideal Bowel Support

Those that don’t want to populate their gut with a myriad of bacteria may want to consider Jarrow Formulas “Ideal Bowel Support” product.  The product consists solely of an L. Plantarum (299v) strain with 10 billion CFUs per capsule.  Many users have testified that this product has improved their gastrointestinal function.

Whether L. Plantarum (299v) is thought to decrease inflammatory biomarkers, preserve cognition, and enhance BNDF production in animals.  Whether something similar occurs among humans that supplement with it isn’t fully understood.  Although this product is a “single strain,” it has relatively low CFUs per capsule compared to others at 10 billion.

  1. ProBiota Bifido

This supplement is comprised of only Bifidobacteria with 10 billion CFUs per serving.  It is manufactured in an inulin-base (derived from chicory root).  Bifidobacteria are considered healthy within the gut and may improve mood and/or anxiety of users.  Within this product, the two strains of bacteria studied in research include Bifidobacterium Longum and Bifidobacterium Breve.

  • Bifidum (4 billion CFUs)
  • Longum (3 billion CFUs)
  • Lactis (2 billion CFUs)
  • Breve (1 billion CFUs)

Though there are 10 billion CFUs per serving, the amount of each bacterium is divided in a hierarchy.  The B. longum strain is delivered at 3 billion CFUs per serving, whereas the B. breve strain is only delivered at 1 billion CFUs per serving.  That said, if you want to solely introduce some potentially therapeutic strains from the Bifidobacterium genus, this is a solid product.

Note: You may be wondering why I didn’t include the product “Nexabiotic” and various others on the above list.  Reasons for exclusion are due to the fact that many contain possibly pathogenic strains of bacteria and/or do not contain any bacterial strains that have been studied for mental health.  Some products that may improve gut health may have lesser impact on brain health than the ones studied in animals and humans.

How to determine the best probiotic for you…

Due to the fact that the technology is not yet available, it is difficult to determine exactly how you’ll respond to a particular probiotic prior to taking it.  This means that you’ll likely need to be your own guinea pig in regards to testing various products and finding what yields the best psychological outcomes.  Keep in mind that you may not respond well to any probiotic and may find them all relatively useless for improving your neurogastroenterological function.  That said, below are some steps you can follow when attempting to find the ideal probiotic.

  1. Consider your psychological state: If you are suffering from a condition such as major depression, you may want to take a different strain of probiotic than someone suffering from anxiety. There may be differences in gut microbiota of those with standalone anxiety compared to those with standalone depression. In forthcoming years, we may be able to pinpoint specific species and subspecies and/or combinations of species that may be ideal for a particular neuropsychiatric condition. Or perhaps we’ll even be able to know which bacteria necessitate upregulation in a specific subtype of a disorder (e.g. social anxiety) compared to another subtype (e.g. OCD).  Although much of the research is limited to animal models (which is low on the evidence pyramid when determining what is likely to work for humans), it may be worth considering when choosing your probiotic.  Someone looking for an antidepressant response may want more B. Animalis whereas someone with anxiety may want more L. Rhamnosus CFUs in the product.
  2. Consider a gut assay: There are assays available that will cost upwards of $400. These involve collecting fecal samples and analyzing them in a laboratory. The microorganism composition within your fecal sample can determine whether you are deficient in certain healthy gut bacteria.  If the assay shows that you are clearly low on a particular bacterial subtype, you can look for it in a probiotic.  Reintroducing the “old friend” that you’ve been missing may substantially improve your mood.
  3. Find a probiotic supplement: As you’ve seen above, I’ve outlined a few probiotics that are seemingly quality products. I have absolutely zero affiliation with any of the companies (in case you were wondering). There may be some great probiotics for sale that simply evaded my research and that you may want to test.  Your goal shouldn’t necessarily be to find the “cheapest” product – as it may get completely obliterated by stomach acids en route to your intestine.
  4. Test it for awhile: After you’ve received a probiotic, start testing. Don’t expect it to work magic in one day – it may take awhile to feel any noticeable difference. That said, I should mention that I felt a noticeable change in my psychological state on the first day of supplementation.  I felt significantly more relaxed than usual, but also dealt with some brain fog – making it difficult for me to finish my work.  Most research suggests that anxiolytic and antidepressant benefits are attained after at least 1 full month of supplementation.  Give it a shot for 4-6 weeks – but obviously cut the testing short if you notice any adverse effects.
  5. Evaluate the results: To accurately determine whether your mood improves or stress is reduced while taking a probiotic, you may want to conduct a pre-test evaluation. Fill out a mood chart and/or anxiety scale and note its severity. Throughout your experience, you may also want to keep a day-to-day journal to document your daily moods and/or anxiety level.  After 30, 60, or 90 days – retake the anxiety or depression test and determine whether any significant improvements were apparent.
  6. Repeat (start new experiment): If after a couple months of supplementation, you derive minimal or zero benefit from the probiotic (in terms of gastroenterological function or neurological function), you may want to discontinue and test another brand. Repeat the experiment with a different strain, set of strains, etc. Assuming you test nearly every probiotic and find no benefit, you may want to test something like daily consumption of fermented foods instead.

Note: You may want to consider fermented foods instead of a probiotic supplement.  Research suggests that fermented foods may reduce anxiety.  Fermented foods contain many more strains of bacteria than are currently documented in the literature.  That said, the drawback of fermented foods is that bacterial contents may be unpredictable based on the specific batch and could contain pathogenic bacteria.

Could the wrong probiotic cause depression and anxiety?

Although most probiotics contain species that are associated with healthy gut function and mental health – they cannot be assumed to treat any condition.  In fact, a subset of users could find that probiotic administration makes their depression and/or anxiety worse.  These substances haven’t been tested extensively in humans, and the impact of various strains on brain function isn’t clear.

A small percentage of probiotics contain a blend of beneficial bacteria, as well as some bacteria that may be pathogenic.  Even though there are likely a greater quantity of healthy bacteria than pathogenic bacteria in these formulations, sensitive individuals may report feeling worse.  Some individuals may also notice certain benefits with other unwanted effects; this could be a sign that certain bacteria are helpful, while others are detrimental.

If there were more single-species probiotics on the market, it would be easier to test strains on oneself and determine which are tolerable and/or yield the greatest benefit.  By testing single species prior to a multispecies formulation, a user would have a better idea as to whether any contents within the multispecies product may yield undesirable effects.  In the future, I wouldn’t be surprised if a company allowed users to format their own probiotics by choosing the specific strains and CFUs they’d like to have included.

In summary, it may be best to do your research and consider sticking with basic strains of probiotics that have been proven to improve neuropsychiatric function in humans – rather than willy-nilly ingesting a probiotic because it has “a ton of strains”; more strains may not necessarily be better.  If you end up feeling worse while taking a particular probiotic, there’s no law mandating continued usage – just stop taking it.  I’ve found that when a specific probiotic alters my psychological state – it generally returns to a homeostatic baseline within several days; activated charcoal administration may expedite recovery.

Other things that can affect your gut bacteria…

Keep in mind that there are many things that can directly alter your gut bacteria besides a probiotic.  Hypothetically speaking, if you are sedentary and don’t get any physical activity on a daily basis – you’ll have dramatically different gut microbiota than if you jogged several miles per day or lifted weights.  The effects of certain lifestyle changes on gut microbiota haven’t been fully elucidated, but consider that your: diet, drug usage, supplement regimen, environment, exercise, sleep, and stress level – can influence your gut, which as is known, can alter brain function.

  • Diet: The foods that you eat on a daily basis will affect the bacteria present in your gut. The macronutrients and micronutrients within your food can influence gut bacteria.  Studies have shown that high-fat diets yield very different gut bacteria from vegan diets, and high protein diets.  Furthermore, the specific types of fats, proteins, and carbs consumed – as well as the quality – can mediate gut bacteria.
  • Drugs: Preliminary evidence suggests that prescription and non-prescription drugs alter gut microbiota. For example, studies have shown that antipsychotics like Zyprexa (Olanzapine) cause weight gain by altering gut bacteria in mice.  It is unclear as to how every drug affects gut bacteria and/or if every drug detrimentally affects gut bacteria – but there is likely an effect on the gut associated with nearly every drug and supplement a person takes.  The most obvious example of drugs that significantly alter gut bacteria are antibiotics.  Antibiotics literally obliterate healthy and pathogenic bacteria simultaneously – potentially leading to GI and psychological distress.
  • Environment: A person’s environment including where they live, how much sun they get, the air quality, toxins, etc. – may be predictive of bacteria that are likely to form in the gut. Inhabitants of Alaska may have significantly different gut bacteria (on average) than people from Hawaii.  Bacterial constituents of the gut lining may change when a person moves to a new house or location.
  • Physical activity: A study published in 2015 documents that one way by which exercise may improve depressive symptoms is by altering bacteria in the gut. While the mechanisms of exercise as an intervention for depression are complex, microbiota alterations may play an important and/or significant role.  Some speculate that regular exercise is associated with fewer pathogenic bacteria in the gut.  Whether a particular type of exercise (e.g. cardio, strength training, walking) is correlated with unique bacteria in the gut (relative to others) is unclear.
  • Sleep: Whether you are getting enough sleep vs. too little sleep may affect your gut bacteria. Chronic sleep deprivation is known to take a significant toll on the brain, and possibly a major toll on gut health.  Those who are chronically sleep deprived may be more likely to exhibit pathogenic gut bacteria than those who regularly get a full night’s sleep.
  • Stress: Individuals who are stressed tend to generate stimulatory neurotransmitters (e.g. norepinephrine) and hormones (e.g. cortisol). Stress also is associated with increased HPA (hypothalamic-adrenal-pituitary axis) activation.  Studies have shown that the norepinephrine produced by stress increases the pathogenicity of Campylobacter jejuni, a harmful bacterium.
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26556075
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17185353/

Which comes first, the chicken (psychiatric diagnosis) or the egg (dysbiosis)?

It is important to note that correlation of a specific psychiatric illness with species of gut bacteria does not necessarily mean that the abnormal gut caused the condition.  As was already mentioned, the relationship between the gut and the brain is multidirectional.  While pathogenic gut bacteria could certainly be a direct, standalone cause of certain psychiatric disorders among a subset of individuals – it may have not been a causative factor for others.

For some individuals, it may be that gut dysbiosis is a causative factor in the pathogenesis of a particular condition, but it may only contribute to a small extent.  For example, someone with schizophrenia may have developed the condition in part because of pathogenic bacteria in the gut, but these bacteria may have only played tiny role in the disease onset.  Therefore, it is important to avoid assuming that simply “fixing the gut” is some utopian treatment or preventative intervention.

To briefly summarize, gut bacteria may be: (1) more of a symptom or byproduct of a condition (than cause of that condition), (2) a 100% direct cause, or (3) a partial cause of varying weightedness (possibly synergistic with another cause) depending on the individual.  Consider that all three aforestated possibilities may occur rather than assuming one is the absolute, definitive explanation.  That said, regardless of whether the “chicken” (psychiatric condition) or “egg” (dysbiosis) came first, evidence does suggest that fixing the gut may improve neurophysiological function.

Therefore, regardless of whether the gut caused a particular condition to develop, some health benefits should theoretically be attained by correcting dysbiosis associated with the condition.  As a result of this dysbiosis correction, some neuropsychiatric symptoms associated with probiotic treatment may be attenuated.  The degree of attenuation and/or general health improvement may be subject to interindividual variation based upon: degree of dysbiosis, extent to which dysbiosis altered neuropsychiatric function, genetics/epigenetics, specific probiotic, dosing regimen, other medications, etc.

Have you tried probiotics for your depression, anxiety, or mental health?

If you’ve tried probiotics for your depression, anxiety, or brain health, have you noticed any significant benefits?  To help others get a better understanding of your particular situation, mention the specific probiotic product that you’re taking, as well as the specific strains of bacteria within that product, and the total CFU (colony forming units).  Assuming your probiotic has had no effect on your overall health, have you considered that the particular product you’re taking isn’t actually delivering the bacteria to your gut?

Many probiotic products are hypothesized to deliver the beneficial bacteria to your gut, completely unadulterated.  The problem is that many times the product will have spoiled and/or the bacteria will die off well before they can proliferate within your gut.  If you believe that a particular probiotic is working well for you, have you considered a possible placebo effect and/or been able to dismiss such an effect?

Since there is a bidirectional relationship between the brain and the gut, perhaps even if there is a placebo effect it could yield benefit for your gut health via CNS-to-ENS signaling.  That said, if you want to rule out a placebo effect, you could pursue a gut assay via a kit that involves mailing in a stool sample.  The stool sample is analyzed and a microbial profile is created for your particular gut to highlight pathogenic bacteria, fungi, and parasites.

Unfortunately, this stool sample is considered costly by average standards between $400 and $600 – depending on the company.  It may be helpful to receive an assay pre-probiotic, pre-prebiotic, or pre-fermented food consumption –  then compare it several months later to determine how your gut has changed.  You may want to also evaluate your mood with objective criteria and attempt to elucidate correlates between pathogenic bacteria and your well-being.

In conclusion, it seems as though administration of certain bacterial strains has potential to optimize gut health and ultimately reduce the likelihood of depression and anxiety.  It is unclear as to whether modifying gut bacteria will provide significant benefit to all individuals with psychiatric disorders.  That said, there is ample evidence to suggest probiotics (or “psychobiotics”) can attenuate certain symptoms of neuropsychiatric disorders in humans.

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{ 11 comments… add one }
  • Eggs For Breakfast March 7, 2016, 5:49 am

    Neat. I’ve been hoping to find a nice summary/discussion this topic. I really enjoy reading your mini literature searches – they’re very thorough and accessibly written. Thanks for writing this!

  • mark March 13, 2016, 9:33 pm

    I have one question and one comment. I am trying to reach you but cannot find a private email on this website. My comment: I have read most of the 20-30 reviews on Psychobiotics on Pubmed and this is the most well documented, balanced one that I have found. Thank you so much for your valuable work. Recent work on autoimmune disorders indicates that many victims suffer from various forms of mental illness and may have less diversity of gut flora.

    I am presently taking a nine strain d-lactate free probiotic powder, containing many of the bacteria mentioned in this review. I had mild headaches for about five days (a sign that my less symbiotic bacteria were not happy with their new neighbors) and after that experienced a surge in energy, the same pleasant sort of energy one gets by working out regularly, that I am now modulating by tweaking the dosage. Powerful stuff.

    • marianne March 14, 2016, 2:15 am

      Was just wondering if you are using the Custom Probiotics d-lactate free probiotic? Also, there is a site, cfsremission.wordpress.com, that has an incredible amount of information on probiotics, all based on research the author has done on PubMed.

      • mark March 15, 2016, 12:03 pm

        Yes, you guessed it… I have no links to that company but they are one of the few that supply d lactate free probiotics and that sell individual strains. Thanks for the tip.

  • Hannah-Phoebe July 11, 2016, 1:44 pm

    This is a wonderful and wonderfully written resource, thank you so much for compiling it.

  • marcel July 21, 2016, 5:01 pm

    Wow – excellent work!

  • sarah July 31, 2016, 10:06 am

    Thank you! Thank you! for writing such a comprehensive article. My sister has struggled with IBS and anxiety for so long, and at last she tried Align, which has B. Infantis. It helped her a lot, but left her very constipated. I also had mild depression, and I now take Jamieson Sticks Probiotic (B. Longum and Lactobillus helveticus) – it helps my mild depression, but it also left me constipated. I deal with this by taking this probiotic every 3 or 4 days.

  • CBL September 1, 2016, 10:08 am

    What a great article, really interesting and I really appreciate the science and studies backing things up. I’m taking 3 of these a day “Probiotic Bacteria Complex 15 billion CFU containing: Lactobacillus acidophilus 3.75 billion, Lactobacillus rhamnosus 3 billion, Bifidobacterium lactis 2.25 billion, Lactobacillus casei 1.5 billion, Bifidobacterium breve 1.5 billion, Bifidobacterium longum 1.5 billion, Bifidobacterium bifidum 750 million, Streptococcus thermophilus 750 million, Fructo oligosaccharides (FOS) 660 mg”, plus Sacchromyces Boulardii and the difference is quite incredible. I am much perkier, less tired, my stomach is less sore and the brain fog is lessening daily.

  • J bas September 10, 2016, 12:14 pm

    Very informative. I wish the medical world would wake up too the reason why so many people are suffering all sorts of symptoms from an imbalance in their gut. If the gut is not right than the rest of your body cannot function well.

  • Jon October 3, 2016, 7:53 pm

    I am using this: https://www.amazon.com/gp/product/B0050FKPU0/ as it includes 9 of the listed bacteria. It doesn’t appear to have the TOS prebiotic. Maybe I should consider adding that? Just started a week ago, so we’ll see… Jon

  • John Macgregor October 21, 2016, 8:26 am

    An extremely good rundown, thanks.

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