Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial

Jessica E Green; Amelia J McGuinness; Michael Berk; David Castle; Eugene Athan; Christopher Hair; Philip Strandwitz; Amy Loughman; Andrew A Nierenberg; John F Cryan; Mohammadreza Mohebbi; Felice Jacka

doi:10.1186/s40814-023-01235-z

Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial

Pilot Feasibility Stud. 2023 Jan 9;9(1):5. doi: 10.1186/s40814-023-01235-z.

Authors

Jessica E Green^{1

2

3}, Amelia J McGuinness⁴, Michael Berk^{4

5

6

7

8}, David Castle⁹, Eugene Athan^{4

8

10}, Christopher Hair⁸, Philip Strandwitz¹¹, Amy Loughman⁴, Andrew A Nierenberg^{12

13}, John F Cryan¹⁴, Mohammadreza Mohebbi⁴, Felice Jacka^{4

15

16

17}

Affiliations

¹ Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia. jegreen@deakin.edu.au.
² Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Australia. jegreen@deakin.edu.au.
³ Department of Psychiatry, Peninsula Health, Frankston, Australia. jegreen@deakin.edu.au.
⁴ Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
⁵ Department of Psychiatry, University of Melbourne, Parkville, Australia.
⁶ Orygen Youth Health Research Centre and the Centre of Youth Mental Health, Melbourne, Australia.
⁷ The Florey Institute for Neuroscience and Mental Health, Parkville, Australia.
⁸ Barwon Health, Geelong, Australia.
⁹ Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Canada.
¹⁰ School of Medicine, Deakin University, Geelong, Australia.
¹¹ Holobiome, Inc., Boston, MA, USA.
¹² Dauten Family Center for Bipolar Treatment Innovation, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹³ Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Anatomy and Neuroscience, University College Cork and APC Microbiome, Cork, Ireland.
¹⁵ Centre for Adolescent Health, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
¹⁶ Black Dog Institute, Melbourne, Australia.
¹⁷ James Cook University, Townsville, Australia.

Abstract

Background: Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD.

Methods and design: This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters.

Discussion: Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need.

Trial registration: Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864.

Keywords: Depression; Faecal microbiota transplantation; Major depressive disorder; Mental disorder; Mental health; Microbiome; Mood disorders; Neuroscience; Psychiatry; RCT.