PR001952 (Project)

Description:Antibiotics cause collateral damage to resident microbes that is associated with various health risks. To-date, studies have largely focused on impacts of antibiotics on large intestinal and fecal microbiota. Here, we employ a GI-wide integrated multiomic approach to reveal that amoxicillin (AMX) treatment reduces overall bacterial abundance, bile salt hydrolase activity and unconjugated bile acids in the small intestine (SI). An accompanying loss of fatty acids and increase in acyl-carnitines in the large intestine corresponded with spatially-distinct expansions of proteobacteria. Parasutterella excrementihominis utilized fatty acid biosynthesis, becoming dominant in the SI while multiple Klebsiella species employed fatty acid oxidation during expansion in the large intestine. Depletion of bile acids and lipids may contribute to AMX-induced dysbiosis in the lower GI. To test this, we demonstrate that restoration of unconjugated bile acids can mitigate losses of commensals in the large intestine while also inhibiting the expansion of Proteobacteria during AMX treatment.