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Glutamine deficiency links clindamycin-induced dysbiosis and intestinal barrier dysfunction in mice

Published online by Cambridge University Press:  22 October 2020

Jinyan Mao
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China
Yongheng Yan
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China
Hongling Li
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China
Xudan Shen
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China
Hao Zhang
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, People’s Republic of China
Haitao Li
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China
Wei Chen
Affiliation:
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, People’s Republic of China Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology & Business University, Beijing 100048, People’s Republic of China
Corresponding

Abstract

Antibiotics rank as the most powerful weapons against bacterial infection, but their use is often limited by antibiotic-associated diarrhoea (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 exposure, evidenced by a dramatic decrease in intestinal glutamine level and glutaminase expression. Mechanistically, clindamycin substantially confounded the abundance of butyrate-producing strains, leading to the deficiency of faecal butyrate which is normally a fundamental fuel for enterocytes, and in turn increased the compensatory use of glutamine. In addition to its pivotal roles in colonic epithelial cell turnover, glutamine was required for nitric oxide production in classic macrophage-driven host defence facilitating pathogen removal. Importantly, oral administration of glutamine effectively attenuated clindamycin-induced dysbiosis and restored intestinal barrier dysfunction in mice. Collectively, the present study highlighted the importance of gut microbiota in host energy homoeostasis and provided a rationale for introducing glutamine supplementation to patients receiving long-term antibiotic treatment.

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Copyright
© The Author(s), 2020. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

Jinyan Mao and Yongheng Yan contributed equally to this work.

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