Fecal microbiota transplantation (FMT) aims to modify the gut microbiome and holds promise as a new treatment approach for major depressive disorder (MDD).
Early case studies report improvements in depressive symptoms following fecal microbiota transplantation (FMT), but larger controlled trials are needed to substantiate its efficacy.
- Two patients with long-standing major depression received FMT as add-on therapy in a pilot trial. Both showed improved depression scores 4 weeks after FMT.
- One patient had sustained GI benefits and depression improvement 8 weeks after FMT. The other patient’s depressive symptoms began to relapse as GI symptoms returned.
- Patients’ microbial composition changed after FMT, but in different ways. One patient increased in diversity and beneficial microbes, the other decreased in diversity.
- More controlled research is essential to clarify if FMT can safely and effectively treat subsets of depression patients. Optimization of protocols and patient selection is needed.
Source: Frontiers in Psychiatry (2022)
Depression & Gut Microbiome Abnormalities
The gut microbiome refers to the vast community of microbes living in our intestines.
Research over the past decade reveals important links between gut bacteria and brain health.
The so-called “gut-brain axis” involves bidirectional communication via neural, endocrine, and immune pathways.
Studies associate gut microbiome alterations with depression.
For example, patients with major depression have reduced microbial diversity and altered ratios of beneficial versus harmful bacteria compared to controls.
Rodent studies show transferring depression-associated gut bacteria can induce depressive behaviors.
Recent evidence suggests that depression is linked to 12 gastrointestinal diseases such as IBS, NAFLD, GERD, ulcerative colitis (UC), and more.
Exactly how gut dysbiosis contributes to depression is unclear.
Potential mechanisms include microbial production of neuroactive metabolites, effects on tryptophan metabolism, regulation of stress response pathways, and influences on the immune system and inflammation.
This gut-brain relationship has led scientists to hypothesize that manipulating intestinal microbiota could improve psychiatric symptoms in depressed patients. FMT aims to do just that.
What is FMT & How Might it Treat Depression?
FMT involves transplanting fecal bacteria from a healthy donor into a recipient’s gut.
This is done by administering the donor sample into the stomach or colon.
The goal is to durably reshape the recipient’s microbial ecosystem in a healthier direction.
FMT was first used to successfully treat refractory Clostridium difficile infections by restoring intestinal microbial diversity.
More recently, researchers have begun testing FMT for other disorders associated with gut dysbiosis, including irritable bowel syndrome, obesity, and Parkinson’s disease.
There is accumulating preclinical evidence that FMT can reduce depressive behaviors in rodents.
For example, germ-free mice colonized with microbiota from depressed patients exhibit more depressive behaviors than mice receiving healthy donor microbiota.
Based on this, clinicians hypothesize FMT may also benefit patients with major depression.
The First FMT Patients for Depression (Pilot Study)
Researchers at the University Psychiatric Clinics Basel in Switzerland performed a pilot randomized controlled trial of FMT for moderate to severe depression.
They aimed to assess safety and gather initial efficacy data.
Thirty patients were planned to receive either FMT or placebo, in addition to their treatment-as-usual.
However, after treating only 4 patients, the trial was halted for safety reasons following an FDA alert about FMT risks.
Here, we summarize the published case reports from the first two patients who received active FMT prior to the trial’s suspension.
FMT for Depression (2 Case Reports)
- Two female patients in their 50s with long histories of major depression, hospitalizations, and suicide attempts
- Both had failed to achieve remission on medications, psychotherapy, electroconvulsive therapy, etc.
- At enrollment, they had moderate-severe depression based on the Hamilton Depression Rating Scale
- Both also had gastrointestinal issues – predominantly constipation
- After baseline assessments, each received a single dose of 30 FMT capsules derived from healthy donors
- They were monitored weekly for 8 weeks post-FMT
Depression Scores Improved After Fecal Microbiota Transplantation
Four weeks after their single FMT dose, both patients’ depression scores were substantially reduced:
- Patient 1’s score dropped 52%, from severe to mild depression
- Patient 2’s score dropped 68%, from severe to mild depression
Additionally, both patients reported feeling better on a subjective depression questionnaire.
However, at the 8 week follow-up:
- Patient 1’s depression score had increased to moderate severity again
- Patient 2 remained mildly depressed, but her score rose slightly
This suggests the FMT treatment effect may diminish over time. Larger trials are needed to clarify duration of benefit.
FMT Also Helped Constipation in One Patient
Both patients experienced gastrointestinal symptoms along with depression. After FMT:
- Patient 1 showed dramatic improvement in constipation, stomach pains, bloating, and other symptoms
- These benefits persisted at 8 weeks
- Patient 2 had little change in constipation and bloating initially. By 8 weeks she had marginal improvement.
This aligns with previous FMT studies showing greater benefits in patients whose gastrointestinal symptoms also improve.
It suggests the depression and GI effects of FMT may be linked.
Examining How FMT Changed Gut Bacteria
The patients gave stool samples before FMT and 4 and 8 weeks after.
Researchers analyzed these to see how the microbiome changed.
Initially, both patients had dysbiosis typical of depression – decreased diversity, reduced beneficial microbes, and increased potentially harmful groups.
Patient 1, who had better clinical outcomes, showed increased diversity and several favorable microbial shifts after FMT.
For example, increases in beneficial bacterial genera and groups that produce helpful compounds like short chain fatty acids.
In contrast, Patient 2 had minimal improvement in diversity or growth of beneficial microbes.
She also developed increased levels of inflammatory markers like fecal calprotectin.
Together this indicates Patient 1 had a more favorable gut microbiome response to FMT.
This may have contributed to her better symptom improvement, especially in GI domains.
Considerations for Using FMT to Treat Depression
This early case study provides preliminary evidence that FMT could potentially improve depressive symptoms for some patients.
However, there are important caveats and questions to address through further research:
- These results need to be replicated in larger controlled trials to truly determine efficacy and safety of FMT for depression.
- Optimal FMT protocol factors remain unclear – best donor and recipient matching strategies, delivery methods, dosing, etc.
- Identifying specific patient characteristics or microbiome biomarkers associated with better response could help select ideal candidates.
- Durability of depression benefits is uncertain. Repeated FMT dosing may be necessary to maintain remission.
- Mechanisms need clarification. GI symptom improvement may mediate depression benefits, but other pathways likely also play a role.
- Safety risks of FMT must be carefully defined and mitigated, especially regarding infection transmission.
With additional well-designed trials, FMT could reveal itself as a useful adjuvant treatment for depression in coming years.
But there is more science still needed for it to be translated into standard clinical practice.
- Paper: Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression – Case Report (2022)
- Authors: Jessica P.K. Doll et al.