Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial

Abstract

Objectives Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. Methods The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial ( n = 15) of enema-delivered FMT ( n = 10) compared with a placebo enema ( n = 5) in adults with moderate-to-severe MDD. Results Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. Conclusions All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.

The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders

“…Depression is a heterogeneous mood disorder with a complex yet not sufficiently understood neurobiology that has strong links to a dysfunction of the microbiome-gut-brain axis (Gheorghe et al, 2022). Clinical studies have found differences in the composition of the gut microbiota in patients with depression compared to individuals without mental disorders (Valles-Colomer et al, 2019;Socała et al, 2021;Green et al, 2023;Modesto Lowe et al, 2023). Common to all studies is an increase in the number of lactic acid-producing bacteria such as Lactobacillus, Streptococcus, and Enterococcus, and a decrease in the number of bacteria producing SCFAs (mainly butyrate) such as Faecalibacterium and Coprococcus (Table 4) (Valles-Colomer et al, 2019;McGuinness et al, 2022).…”

“…There is evidence of a correlation between certain gut bacteria and depression symptoms (Simpson et al, 2021;McGuinness et al, 2022). However, their involvement in the pathophysiology of the mental disorder is not well understood (Green et al, 2023). Meta-analyses suggest that probiotics as an adjunctive treatment may reduce depressive symptoms, (Chao et al, 2020;El Dib et al, 2021;Green et al, 2023).…”

“…However, their involvement in the pathophysiology of the mental disorder is not well understood (Green et al, 2023). Meta-analyses suggest that probiotics as an adjunctive treatment may reduce depressive symptoms, (Chao et al, 2020;El Dib et al, 2021;Green et al, 2023). However, probiotic preparations to date are limited to a single bacterial strain or, at best, a small number of strains (Green et al, 2023).…”

“…Meta-analyses suggest that probiotics as an adjunctive treatment may reduce depressive symptoms, (Chao et al, 2020;El Dib et al, 2021;Green et al, 2023). However, probiotic preparations to date are limited to a single bacterial strain or, at best, a small number of strains (Green et al, 2023). In contrast, fecal microbiota transplantation (FMT), which encompasses the complete human gut microbiome containing thousands of potentially symbiotic strains (Strandwitz et al, 2019), may be better suitable since it alters the composition of the gut microbiota more effectively (Green et al, 2023).…”

Just a gut feeling: Faecal microbiota transplant for treatment of depression – A mini-review

“…A pilot double-blind randomised controlled study (RCT) in humans by Green et al (2023) demonstrated good feasibility, acceptability and safety of FMT enemas in the treatment of MDD. All feasibility targets were met or exceeded, and the findings are encouraging and support further research into FMT.…”