Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review

Raghunath Singh; Kristoffer Panganiban; Emily Au; Rekha Ravikumar; Sandra Pereira; Thomas D Prevot; Daniel J Mueller; Gary Remington; Sri Mahavir Agarwal; Elena F Verdu; Premysl Bercik; Giada De Palma; Margaret K Hahn

doi:10.1016/j.ajp.2024.104285

Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review

Asian J Psychiatr. 2024 Oct 24:102:104285. doi: 10.1016/j.ajp.2024.104285. Online ahead of print.

Authors

Affiliations

¹ Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
² Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³ Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
⁵ Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada.
⁶ Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada.
⁷ Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁸ Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Banting and Best Diabetes Centre (BBDC), Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁹ Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹⁰ Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Banting and Best Diabetes Centre (BBDC), Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].

PMID: 39486191
DOI: 10.1016/j.ajp.2024.104285

Abstract

More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.

Keywords: Animal model; Fecal microbiota transplantation; Gut microbiome; Gut-brain axis; Schizophrenia.

Publication types

Review