Serotonin Promotes Enterohemorrhagic Escherichia Coli Pathogenesis Through Altered AI‐2 Production by Gut Microbiota

Abstract

The overall goal of this study is to investigate the cross‐talk between a host metabolite (serotonin), the commensal bacterial community, and a microbial signaling molecule (Autoinducer‐2; AI‐2), in the etiology of Enterohemorrhagic Escherichia coli (EHEC) infections. A broad range of microbial (e.g., AI‐2, indole) and host metabolites (e.g., neuroendocrine hormones such as serotonin and norepinephrine) are present in the GI tract microenvironment and often function together to modulate the virulence of enteric pathogens. Serotonin is of specific interest as it is abundant in the GI tract and has pleiotropic roles on intestinal physiology. While it is well established that serotonin levels increase during inflammation, its impact on the commensal microbiota composition and function, and thereby, on enteric pathogen infections is poorly understood. Here we show that serotonin exposure results in a statistically significant increase (p<0.05) in the production of AI‐2 produced by non‐pathogenic E. coli and EHEC. Serotonin exposure also increased the expression of virulence genes (eaeA, escC, and escV) in EHEC in vitro and this increase depends on the luxS gene that is required for AI‐2 production. Based on these results, we hypothesize that serotonin's effects on EHEC virulence are mediated through AI‐2. Administering serotonin in mice resulted in pronounced dysbiosis of the microbiota composition. Interestingly, approximately 50% of the bacterial communities that showed a significant fold change (p<0.05) at the genus level had representative members with the luxS gene. Significant changes were also observed in the levels of six tryptophan‐derived microbiota metabolites including a reduction in the levels of indole. Together, our results support a model in which an increase in serotonin causes microbiota dysbiosis, increases AI‐2 levels, downregulates the beneficial anti‐inflammatory metabolites, thereby creating a niche favorable for EHEC colonization. Understanding the specific mechanisms underlying the effect of serotonin on the microbial community can lead to the development of new therapeutic approaches for combating enteric infections.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.