Effect of Norepinephrine on Gut Bacterial Community Structure and Function

Abstract

Metabolites produced by both the microbial community and the host are present in the gastrointestinal tract environment. Several metabolites have been identified as important mediators of different physiological functions in the host. Small molecules and metabolites produced by commensal bacteria resident in the gastrointestinal tract can both promote and attenuate colonization of pathogens and inflammation. However, interactions between different metabolites in the GI tract and their net effect on the host are poorly understood. We hypothesized that NE promotes EHEC virulence by altering the microbial community structure and function to facilitate colonization. An in vitro anaerobic batch culture system was used to investigate the effect of NE on the microbial community structure and function. Cecal contents from 6–8 week‐old mice (n = 7) were both collected and cultured anaerobically in Gut Microbiota Medium (GMM) with or without NE (500μM) at 37°C for seven days. Exposure to NE increased the diversity of the bacterial community (p < 0.05, Mann‐Whitney test), as determined from 16S rRNA sequencing. Genera containing facultative pathogens and reported with pro‐inflammatory roles like Hathewaya, Clostridium and Streptococcus were highly abundant in the NE group while beneficial bacterial genera like Lactobacillus were decreased in abundance with NE treatment. Untargeted LC‐MS metabolomics showed significant changes in the levels of metabolites derived from aromatic amino acids. Targeted LC‐MS metabolomics analysis confirmed that the tryptophan metabolites indole and 5‐hydroxyindole were significantly decreased and tyramine was increased with NE treatment (p < 0.05, Wilcoxon test). Integration of metabolomic and metagenomic data using partial least squares regression (PLS‐R) showed correlation between the downregulation of indole and indole producing bacteria in the presence of NE. NE also down‐regulated the expression of the enzyme Tryptophanase A (TnaA) that is required for the conversion of dietary tryptophan to indole, in both nonpathogenic E. coli and EHEC. These results suggest that NE can modulate the microbial community composition and metabolite output to potentially increase pathogen colonization and infection.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.