Food and Behaviour Research

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

Ioana A. Marin, Jennifer E. Goertz, Tiantian Ren, Stephen S. Rich, Suna Onengut-Gumuscu, Emily Farber, Martin Wu, Christopher C. Overall, Jonathan Kipnis & Alban Gaultier (2017) Nature Scientific Reports 7,  Article number: 43859 (2017) doi:10.1038/srep43859 

Web URL: Read the abstract and full article on Nature here

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.

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