Integrative analysis of microbiome and metabolome in mouse model simulating features of post‐traumatic stress disorder (982.1)

Abstract

The gastrointestinal tract is colonized by an enormous array of microbial symbiotes and pathogens. The symbiote influence of gut microbiota on the nervous system and behavior has been receiving profound interest. Rodent studies have provided suggestive evidence that probiotics (e.g. Lactobacillus and Bifidobacterium) can influence behavior. Using “cage‐within‐cage resident‐intruder” model, subject C57BL/6J mice were exposed to aggressors for 6 h daily for 5 or 10 days. After one day of recovery inflammatory cardiac histopathologies were prevalent. Here we report metagenomics and metabolomics approaches to understanding the microbiome activity in our social stress model of mice. Plasma samples were compared between aggressor‐exposed and control mice using various Mass Spec‐based techniques. Large effects of microbiome composition on plasma biochemistry were observed, and several microbiome‐affected molecules such as hippurate, phenylpropionylglycine, and 3‐phenylpropionic were identified in plasma. We also sequenced the 16S rRNA gene V4 variable region on DNA from duodenum tissue using an ion torrent Personal Genome Machine platform. A significant increase of Lactobacillus in the socially stressed mice compared to the control group was observed. Together, these data demonstrate that prolonged stress can significantly change the composition of the intestinal microbiome. We are in the process of analyzing possible correlations between host microbiome population structure and accumulation of metabolites in plasma.DISCLAIMER “Research was conducted in compliance with the Animal Welfare Act and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.”