Randomized Controlled Trial

. 2023 May;68(5):315-326.

doi: 10.1177/07067437221150508. Epub 2023 Jan 13.

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

Jessica Emily Green^{1

2

3}, Michael Berk^{1

4}, Mohammadreza Mohebbi^{1

5}, Amy Loughman¹, Amelia J McGuinness¹, David Castle⁶, Mary Lou Chatterton^{7

8}, Joahna Perez⁷, Philip Strandwitz⁹, Eugene Athan^{1

10

11}, Christopher Hair¹⁰, Andrew A Nierenberg^{12

13}, John F Cryan¹⁴, Felice Jacka^{1

15

16}

Affiliations

¹ Deakin University, Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation, Geelong, Victoria, Australia.
² Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Australia.
³ Department of Psychiatry, Peninsula Health, Frankston, Australia.
⁴ Department of Psychiatry, University of Melbourne, Parkville, Australia.
⁵ Faculty of Health, Biostatistics Unit, Deakin University, Geelong, Australia.
⁶ Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Parkville, Australia.
⁷ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁸ Institute for Health Transformation, Deakin University, Geelong, Australia.
⁹ Holobiome, Boston, MA, USA.
¹⁰ School of Medicine, Barwon Health, Geelong, Australia.
¹¹ School of Medicine, Deakin University, Geelong, Australia.
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, County Cork, Ireland.
¹⁵ Centre for Adolescent Health, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
¹⁶ College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Australia.

PMID: 36637229
PMCID: PMC10192831
DOI: 10.1177/07067437221150508

Randomized Controlled Trial

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

Jessica Emily Green et al. Can J Psychiatry. 2023 May.

. 2023 May;68(5):315-326.

doi: 10.1177/07067437221150508. Epub 2023 Jan 13.

Authors

Affiliations

¹ Deakin University, Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation, Geelong, Victoria, Australia.
² Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Australia.
³ Department of Psychiatry, Peninsula Health, Frankston, Australia.
⁴ Department of Psychiatry, University of Melbourne, Parkville, Australia.
⁵ Faculty of Health, Biostatistics Unit, Deakin University, Geelong, Australia.
⁶ Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Parkville, Australia.
⁷ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁸ Institute for Health Transformation, Deakin University, Geelong, Australia.
⁹ Holobiome, Boston, MA, USA.
¹⁰ School of Medicine, Barwon Health, Geelong, Australia.
¹¹ School of Medicine, Deakin University, Geelong, Australia.
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, County Cork, Ireland.
¹⁵ Centre for Adolescent Health, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
¹⁶ College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Australia.

PMID: 36637229
PMCID: PMC10192831
DOI: 10.1177/07067437221150508

Abstract
in English, French

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.

Objectif: Les perturbations du microbiote intestinal ont été associées aux troubles de santé mentale, notamment le trouble dépressif majeur (TDM). Par conséquent, la transplantation du microbiote fécal (TMF) est prometteuse à titre de traitement de modulation du microbiote pour le TDM. Pourtant, à ce jour il n'y a pas d'études contrôlées publiées qui évaluent l'utilisation de la TMF pour le TDM. La présente étude visait à corriger cet écart en évaluant la faisabilité, l'acceptabilité et la sécurité de la TMF pour le TDM. Méthodes : L'étude était un essai pilote randomisé contrôlé (n = 15), de 8 semaines, à double insu, en groupes parallèles 2:1, d'une TMF administrée par lavement (n = 10) comparé à un lavement placebo (n = 5) chez des adultes souffrant d'un TDM modéré à grave. Résultats : Le recrutement s'est fait en 2 mois, avec 0 % d'attrition et 100 % de participation aux principaux rendez-vous de l'étude. Il n'y a pas eu de déviation majeure du protocole. Les stratégies du placebo et du double insu ont été estimées réussies; les infirmières et les participants ont correctement deviné leur affectation de traitement à un rythme semblable à celui anticipé par hasard. Aucun événement indésirable sérieux ou grave n'a été déclaré dans aucun groupe et il n'y a pas eu de différences significatives entre les événements indésirables bénins à modérés entre les groupes (la médiane de deux événements indésirables par participant rapportée dans les deux groupes). En outre, les 12/15 participants qui ont rempli le sondage sur la satisfaction du participant à la 2e semaine étaient d'accord ou fortement d'accord que l'administration du lavement était tolérable, et qu'ils suivraient le traitement de nouveau, si nécessaire. Bien que l'étude ne soit pas conçue pour mesurer les résultats cliniques, les données exploratoires ont aussi suggéré que le traitement actif de la TMF peut entraîner des améliorations des symptômes gastro-intestinaux et de la qualité de vie dans cette population, en faisant remarquer que le syndrome du côlon irritable est communément comorbide avec le TDM. Conclusions : Toutes les cibles de faisabilité ont été satisfaites ou excédées. Cette étude a constaté que la TMF administrée par lavement est faisable, acceptable, bien tolérée et sécuritaire chez les patients souffrant du TDM. Les résultats de cette étude soutiennent plus de recherche pour évaluer l'efficacité clinique, et l'usage de ce protocole est soutenu.

Keywords: FMT; MDD; depression; faecal microbiota transplantation; major depressive disorder; mental disorder; mental health; microbiome; mood disorders; psychiatry.

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

Affiliations

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

Authors

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Abstract
in English, French

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Abstract in English, French

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Abstract
in English, French