Microbiota alteration is associated with the development of stress-induced despair behavior

Abstract

Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.

Yeast fermentate prebiotic improves intestinal barrier integrity during heat stress by modulation of the gut microbiota in rats

“…Some of them observed an increase of Lactobacillus spp. during chronic stress (Wong et al, ), while others reported about depleting of these bacteria in stressed animals (Marin et al, ). Treatment with EH did not change the relative abundance of Lactobacillus spp.…”

Lactobacillus plantarumMTCC 9510 supplementation protects from chronic unpredictable and sleep deprivation-induced behaviour, biochemical and selected gut microbial aberrations in mice

“…One recent study also suggesting a beneficial effect of a potential probiotic strain of lactobacilli in stress‐induced anxiety and depression (Marin et al . ). Despite the increasing evidences suggesting a link between gut microbial dysbiosis with stress and neuropsychiatric disorders, the underlying mechanisms are not fully understood.…”

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

“…; Marin et al . ), as well as the supplementation of host‐indigestible dietary fibres that are fermented by the gut microbiota (prebiotics) (Burokas et al . ).…”