Is Fecal Transplantation Effective for Depression?

Fecal microbiota transplantation (FMT) may be an effective adjunctive therapy for depression, especially in patients with symptoms linked to gut disorders such as irritable bowel syndrome (IBS). However, experts caution that the evidence is preliminary.

A large meta-analysis showed that FMT significantly reduced depressive symptoms in the short and medium term. Both oral capsule and direct gastrointestinal (GI) delivery were effective, although the benefits were greater with direct GI administration.

However, the researchers cautioned that the overall quality of the evidence was rated as low to very low and highlighted the need for more robust and targeted research.

The study was published online on October 5 in Frontiers in Psychiatry.

Does Fixing the Gut Boost Mood?

Depression, which affects over 280 million people globally, is increasingly linked to gut microbiome imbalances.

FMT involves transferring gut bacteria from a healthy donor into a recipient’s GI tract to restore microbial balance. Long used for recurrent Clostridioides difficile infections, it is now under investigation for conditions linked to the gut-brain axis.

Preclinical and clinical work suggests that restoring healthy microbial diversity may influence inflammation, neurotransmitter activity, and mood regulation. Yet current evidence on FMT for depression is “fragmented and inconclusive,” the researchers, with first author Xiaotao Zhang, of Nanjing University of Chinese Medicine, Nanjing, China, wrote.

To gain a better understanding of the therapeutic potential of FMT for depressive symptoms, they synthesized data from 12 randomized controlled trials with 681 participants across China, Australia, Canada, Finland, and the US.

All trials consistently evaluated the impact of FMT on depressive symptoms whether as a primary or secondary outcome using validated scales such as the Hamilton Depression Rating Scale, Montgomery-Åsberg Depression Rating Scale, and Hospital Anxiety and Depression Scale.

The trials included patients with various conditions. Five trials focused on IBS and one on ulcerative colitis. Two trials targeted neurologic disorders including progressive supranuclear palsy-Richardson syndrome and Parkinson’s disease with comorbid GI disorders.

Four trials included patients with COVID-19 experiencing diarrhea and depressive symptoms, severe obesity with insulin resistance, or fibromyalgia. Only one trial specifically included patients diagnosed with major depressive disorder (MDD).

The pooled results showed a significant reduction in depressive symptoms in the FMT group compared to the control group (standardized mean difference [SMD], -1.21; P = .0003).

Although the included studies were highly heterogeneous, sensitivity analyses showed that depressive symptom scores were significantly improved in the FMT group compared with the control group (SMD, -0.56; P = .0003).

Subgroup analysis showed stronger effects in patients with IBS (SMD, -1.06) than in those with neurologic/psychiatric-related conditions (SMD, -0.67), with moderate heterogeneity.

Both oral capsules and direct GI administration (via endoscopy or enema) were effective, with slightly greater effects observed for direct GI delivery (SMD, -1.29 vs -1.06).

Improvement in depressive symptoms was most notable in short- to mid-term follow-up, with the effects diminished by 6 months.

To advance the field, the researchers recommended that future trials focus on clinically diagnosed depression, use standardized FMT protocols, and include long-term follow-up to evaluate sustained effects on depressive symptoms. They also emphasized the need to systematically account for factors such as diet, medications, and psychological therapies to minimize confounding.

A New Therapeutic Target?

Valerie Taylor, MD, PhD, professor and head of the Department of Psychiatry at the University of Calgary, Calgary, Alberta, Canada, who wasn’t involved in the study, told Medscape Medical News there is a “growing body of research to support really examining the gut microbiome as a therapeutic target in mental illness treatment.”

“While we need to do longer studies to understand dosing and efficacy, this is an exciting new area. This study highlights there is successful translational work occurring in this space,” Taylor said.

Her team in Calgary recently completed a study on FMT for treatment-resistant MDD, which is currently under review, she said.

Jessica Green, MBBS, PhD, consultant psychiatrist and senior research fellow at the Food & Mood Center, Deakin University in Geelong, Australia, also wasn’t involved in the study, but was a reviewer on the paper.

She said that while FMT is a “very promising” potential treatment for depression, the paper is “perhaps more optimistic about its interpretation of the findings than is justified by the preliminary nature of the data at this stage.”

“That’s because the analysis uses data from studies that weren’t designed or powered for measuring depression, and it wasn’t known if a population was clinically depressed or not at baseline; if they weren’t clinically depressed, then improvement in the depression rating scale is not very meaningful,” Green said.

She noted that most of the studies included people diagnosed with a range of disorders including IBS combined with mild-to-moderate anxiety/depression, COVID-19 with associated diarrhea and depressive symptoms and fibromyalgia.

“You would expect mood to be impacted in these patients and if mood improved, it’s unclear whether the improvements were due to FMT or simply because IBS had resolved,” Green said.

Still, Green said there is “every reason theoretically” that FMT could help with depression and “hopefully, we’ll get a better signal soon.”

Note: This article originally appeared on Medscape.