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. 2021 Nov 8;11(1):21869.
doi: 10.1038/s41598-021-01248-9.

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

Julie Kristine Knudsen  1   2   3 , Thomas Yssing Michaelsen  4 , Caspar Bundgaard-Nielsen  1   2 , René Ernst Nielsen  2   5 , Simon Hjerrild  6   7 , Peter Leutscher  1   2 , Gregers Wegener  3   7 , Suzette Sørensen  8   9
Affiliations

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

Julie Kristine Knudsen et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Behavioural analysis of the forced swim test of FSL and FRL rats. Total immobility time (sec) (A,C) and total struggling time (sec) (B,D) of rats from each group of FRL (A,B) or FSL (C,D) rats based on recordings of the first 5 min. P-values were included in the figure if they were below 0.2. Grey lines represent cohoused animals in the FRL group. The red dot represents the rat that was removed from the analysis as mentioned in the Methods section. FMT-MDD: Faecal microbiota transplantation from patients with MDD into rats. FMT-Healthy: Faecal microbiota transplantation from healthy individuals into rats. FMT-MDD-Ser: Faecal microbiota transplantation from patients with MDD into rats combined with treatment with sertraline. CON-Auto: Rats receiving auto-transplantations. CON-H2O: Rats receiving demineralised water.
Figure 2
Figure 2
Stacked bar plots of relative changes in gut microbiota composition of FRL rats. Each bar represents all the OTUs observed across samples from one rat. OTUs in blue were detected in both pre-and post-FMT samples, while OTUs in purple were novel in the rat and not detected in the donor material. The green OTUs were common in both rats and humans, while the red percentage was unique to the human donor material only. FMT-MDD: Faecal microbiota transplantation from patients with MDD into rats. FMT-Healthy: Faecal microbiota transplantation from healthy individuals into rats. FMT-MDD-Ser: Faecal microbiota transplantation from patients with MDD into rats combined with treatment with sertraline.
Figure 3
Figure 3
MA plot presenting the fold change in OTU expression between pre-FMT and post-FMT samples collected from FRL rats. (A) OTU expression in rats receiving faecal microbiota transplantation (FMT) from patients with MDD (FMT-MDD) compared to rats receiving from healthy individuals (FMT-Healthy). Of all the OTUs, seventeen were elevated in FMT-MDD samples, while eight were depleted compared to FMT-Healthy samples. (B) The twenty-five OTUs significantly different between FMT-MDD animals and FMT-Healthy animals. Five of these OTUs, marked by “X”, could be traced to the human donor material. The fold change is expressed as the change in relative abundance of bacteria in the FMT-MDD group compared to the FMT-Healthy group.
Figure 4
Figure 4
Relative mRNA expression of tight junction protein-encoding genes in the caecum of FRL rats. (A) Relative gene expression of ocln in rats. (B) Relative gene expression of cldn3 in rats. Gene expression was normalized against gene expression of Gapdh using the ΔΔCt method. FMT-MDD: Faecal microbiota transplantation from patients with MDD into rats. FMT-Healthy: Faecal microbiota transplantation from healthy individuals into rats. FMT-MDD-Ser: Faecal microbiota transplantation from patients with MDD into rats combined with treatment with sertraline. CON-Auto: Rats receiving auto-transplantations. CON-H2O: Rats receiving demineralised water.
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