Glutamine Deficiency Links Clindamycin-Induced Dysbiosis and Intestinal Barrier Dysfunction in Mice.

Antibiotic rank the most powerful weapons against bacterial infection, but their use is often limited by antibiotic-associated diarrhea (AAD). Here we reported that glutamine deficiency might act as a new link between clindamycin-induced dysbiosis and intestinal barrier dysfunction during AAD progression. Using a mouse model, we demonstrated that glutamine became a conditionally essential amino acid upon persistent therapeutic-dose clindamycin expose, evidenced by a dramatic decrease in intestinal glutamine level and glutaminase expression. Mechanistically, clindamycin substantially confounded the abundance of butyrate-producing strains, lead to the deficiency of fecal butyrate which is normally a fundamental fuel for enterocytes, and in turn increased compensatory use of glutamine. In addition to its pivotal roles in colonic epithelial cell turnover, glutamine was required for nitric oxide (NO) production in classic macrophage-driven host defense facilitating pathogen removal. Importantly, oral administration of glutamine effectively attenuated clindamycin-induced dysbiosis and restored intestinal barrier dysfunction in mice. Collectively, this study highlighted the importance of gut microbiota in host energy homeostasis, and provided a rationale for introducing glutamine supplementation to patients receiving long-term antibiotic treatment.