Abstract (as presented by the authors of the scientific work):
"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."
Covered topics (the letter size corresponds to the frequency of mentioning in the text):
Discussion (as presented by the authors of the scientific work):
"Taken together, our results demonstrate that microbiome homeostasis was robustly altered in animals undergoing UCMS, with a consistent decrease in Lactobacilli. This finding was shared across three strains of mice (C57BL/6J, as BALB/cJ and C57BL/6N). Moreover, our data suggest that the production of H2O2 by Lactobacillus may be protective against the development of despair behavior by direct inhibition of intestinal ido1 expression and decrease in the circulating level of kynurenine, a metabolite associated with depression26.
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Prof. Atanas G. Atanasov (Dr. habil., PhD)