Species-specific enhancement of enterohemorrhagic E . coli pathogenesis mediated by microbiome metabolites

摘要: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice relatively resistant this pathogen. This intrinsic species-specific difference EHEC limits translation murine research human. Furthermore, studying mechanisms underlying differential is a difficult problem due complex vivo interactions between host, pathogen, and disparate commensal microbial communities. We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology model damage human colonic epithelium induced show that epithelial injury greater when exposed metabolites derived from gut microbiome compared mouse. Using multi-omics approach, we discovered four metabolites—4-methyl benzoic acid, 3,4-dimethylbenzoic hexanoic heptanoic acid—that sufficient mediate effect. The active preferentially induce expression flagellin, bacterial protein associated with motility increased injury. Thus, decreased observed versus other species may be part presence compounds produced intestinal actively promote pathogenicity. Organ-on-chip allowed identification specific modulating pathogenesis. These identified increase our Colon Chip they contribute tolerance. work suggests higher concentrations these could reason for certain populations, such as children. lays foundation therapeutic-modulation microbe products order prevent treat infection.