Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour

Julie Kristine Knudsen,Peter Leutscher,Gregers Wegener,René Ernst Nielsen,Thomas Yssing Michaelsen,Simon Hjerrild,Suzette Sørensen,Caspar Bundgaard-Nielsen

doi:10.1038/s41598-021-01248-9

Abstract

Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Here, we investigated if faecal microbiota transplantation (FMT) from patients with MDD into rats could induce a depressive-like phenotype. We performed FMT from patients with MDD (FMT-MDD) and healthy individuals (FMT-Healthy) into male Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats and assessed depressive-like behaviour. No behavioural differences were observed in the FSL rats. In FRL rats, the FMT-Healthy group displayed significantly less depressive-like behaviour than the FMT-MDD group. However, there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria. We additionally found different taxa between the FMT-MDD and the FMT-Healthy FRL rats, which could be traced to the donors. Four taxa, three belonging to the family Ruminococcaceae and the genus Lachnospira, were significantly elevated in relative abundance in FMT-MDD rats, while the genus Coprococcus was depleted. In this study, the FMT-MDD group was different from the FMT-Healthy group based on behaviour and intestinal taxa.

Highlights

Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals
In the Flinders Resistant Line (FRL) rats, there was a tendency towards higher immobility (p = 0.088) and significantly less struggling (p = 0.013) (Fig. 1A,B, respectively) in the faecal microbiota transplantation (FMT)-MDD group compared to the FMT-Healthy group
We explored if a depressive-like phenotype was induced in rats by FMT from treatment-naïve patients with MDD compared to FMT from healthy individuals

Summary

Introduction

Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Studies have observed reduced intestinal tight junction proteins in animals with gut microbiota alterations, which may increase barrier permeability, allowing the translocation of potentially harmful bacterial metabolites, which cannot normally pass this barrier[31,32] This phenomenon, termed ‘leaky gut’, has been hypothesized to be involved in the pathogenesis and development of MDD33,34, as it is speculated that this allows transfer of metabolites leading to increased inflammation[35]. The alterations were plausibly linked to the transplantation of distinct bacteria with specific neuropathophysiological features These studies found behavioural differences between animals receiving FMT from patients with MDD compared to healthy individuals, the applied animal models may have imposed behavioural differences prior to FMT. It was found that depressive behaviours could be linked to dietary components manipulated by the gut microbiota[42], and that probiotics could alter b ehaviour[42,43]

Objectives

Methods

Results

Conclusion