Abstract
RationaleThe gut microbiota is increasingly recognized as a potential mediator of psychiatric diseases. Depressed patients have been shown to have a different microbiota composition compared with healthy controls, and several lines of research now aim to restore this dysbiosis. To develop novel treatments, preclinical models may provide novel mechanistic insights.Objective and methodsWe characterized the gut microbiota of male adult Flinders sensitive line (FSL) rats, an animal model of depression, and their controls, Flinders resistant line (FRL) rats using 16S rRNA amplicon sequencing. Moreover, we performed fecal microbiota transplantation (using saline or pooled FRL/FSL feces) to study if the potential strain-specific differences could be transferred from one strain to the other, and if these differences were reflected in their depressive-like behavior in the forced swim test.ResultsFSL rats tended to have lower bacterial richness and altered relative abundances of several bacterial phyla, families, and species, including higher Proteobacteria and lower Elusimicrobia and Saccharibacteria. There was a clear separation between FRL and FSL rat strains, but no effect of treatment, i.e., the bacterial composition of FSL rats receiving FRL feces was still more similar to FSL and not FRL rats. Similarly, the transplantation did not reverse behavioral differences in the forced swim test, although FSL feces significantly increased immobility compared with saline.ConclusionsOur study showed that the gut microbiota composition of the depressive-like rats markedly differed from their controls, which may be of value for future microbiota-targeted work in this and similar animal models.
Highlights
The gut microbiota is known to be involved in key physiological processes such as nutrient absorption, digestion, and metabolism
Compared with Flinders resistant line (FRL) rats, Flinders sensitive line (FSL) tended to have lower gut microbiota richness as calculated by the number of observed Operational taxonomic unit (OTU) based on 10.000 reads per sample (507.8 ± 87.2 vs. 461.7 ± 76.7; F(1,41) = 3.56, p = 0.066, Fig. 2a)
Multivariate inference revealed a clear separation between FSL and FRL rats To assess whether the microbiota could predict group belonging, we performed a partial least-squares discriminant analysis (PLS-DA) analysis
Summary
The gut microbiota is known to be involved in key physiological processes such as nutrient absorption, digestion, and metabolism. Animal studies provided evidence to both, as stress caused gut microbial changes (O’Mahony et al 2011, Bangsgaard Bendtsen et al 2012, Abautret-Daly et al 2018), Bailey et al 2011) and gut microbiota transplantation from depressed patients induced depressive-like behavior in germ-free mice (Zheng et al 2016) and microbiota-depleted rats (Kelly et al 2016) These effects may be specific to microbiota-depleted models or human-derived feces, but they clearly demonstrate a causal association between gut microbiota and depressive-like behavior. To further explore this relationship, more data on conventional animals raised in nonsterile environments are needed
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