Structural & functional consequences of chronic psychosocial stress on the microbiome & host

Abstract

Introduction: Given the lasting impact of psychological distress on behavior, along with the role of the microbiome in neurobehavioral development, we sought to examine the relationship between the microbiota and stress-induced behavioral deficits.

Methods: Male C57BL/6 mice exposed to chronic social defeat were subjected to behavioral analysis and profiling of the intestinal microbiome. Mice were also analyzed for phenotypic and functional immune changes. A computational approach on 16S rRNA marker gene sequences was used to predict functional changes in the metagenome as a consequence of structural shifts in the microbiota.

Results: Chronic social defeat induced behavioral changes that were associated with reduced richness and diversity of the gut microbial community, along with distinct shifts at the level of operational taxonomic units (OTU) across phyla. The degree of deficits in social, but not exploratory behavior was correlated with group differences between the microbial community profile. In silico analysis predicted a shift in the functional profile of the microbiome: defeated mice exhibited reduced functional diversity and a lower prevalence of pathways involved in the synthesis and metabolism of neurotransmitter precursors and short-chain fatty acids. Defeated mice also exhibited sustained alterations in dendritic cell activation, and transiently elevated levels of IL-10+ T regulatory cells that were suppressed over time.

Conclusions: This study indicates that stress-induced disruptions in neurologic function are associated with altered immunoregulatory responses and complex OTU-level shifts in the microbiota. It is thus suggested that a dysbiotic state, along with specific changes in microbial markers, may predict the onset of adverse neurocognitive deficits commonly observed following exposure to severe stressors. The data also predict novel pathways that might underlie microbiota-mediated effects on brain and behavior, thus presenting targets for investigations into mechanisms and potential therapy.

Keywords: Behavior; Chronic social defeat; Functional metagenome; Gut microbiota; Immune regulation; Psychosocial stress.