Microbial Ecosystem Therapeutics for Major Depression

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Authors

Chinna-Meyyappan, Arthi

Date

2024-01-24

Type

thesis

Language

eng

Keyword

clinical trial , depression , anxiety , microbe therapy , gut brain axis

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Abstract

Background: Research suggests gut microbiota repopulation techniques may elicit an improvement in depressive symptoms via the pathways of the gut-brain axis, a bidirectional communication network between the gut and the brain. Objectives: 1) Systematically review the current literature examining fecal microbiota transplantation (FMT) for psychiatric symptoms in clinical and preclinical populations; 2) Examine the efficacy, safety, and tolerability of microbial ecosystem therapeutic-2 (MET-2) on depression and anxiety symptoms in a pilot study; 3) Formulate a protocol for a double-blind, randomized, placebo-controlled trial (DBRCT) to investigate the impact of MET-2 on depression using knowledge obtained from the pilot study 4) Conduct a comparative analysis of the clinical and molecular effects of MET-2 versus placebo. Methods: After systematically reviewing the current literature to evaluate existing evidence for the use of gut repopulation treatments, I conducted a 10-week open-label pilot study examining the effects of MET- 2, an alternative to FMT that is comprised of 40 lyophilized bacterial cultures for oral consumption. Then I developed a protocol for an 8-week DBRCT to examine MET-2’s efficacy in comparison to a placebo and explore changes in immune biomarkers that may be involved in underlying mechanisms of action of MET-2. Results: The systematic review provided relatively strong evidence for the use of gut repopulation techniques for treatment of depression, though there was minimal evidence in clinical populations and a lack of DBRCTs. The pilot results showed promising evidence for using MET-2 in alleviating mood and anxiety symptoms. These findings were not supported by the DBRCT. Though there were significant improvements in mood and related symptoms scores, these were not significantly different between placebo and MET-2 groups. There were also no significant changes in immune biomarkers. However, the response rate data and clinically significant trends seen between the two groups in the clinical data were promising. Conclusions: The findings presented in this thesis are the first to provide evidence for the role of MET-2 in alleviating symptoms of depression and compare its use to a placebo alternative. They provide crucial future directions for gut repopulation research in the context of psychiatric indications.

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