Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome

Aibo Gao, Junlei Su, Ruixin Liu, Shaoqian Zhao, Wen Li, Xiaoqiang Xu, Danjie Li, Juan Shi, Bin Gu, Juan Zhang, Qi Li, Xiaolin Wang, Yifei Zhang, Yu Xu, Jieli Lu, Guang Ning, Jie Hong, Yufang Bi, Weiqiong Gu (), Jiqiu Wang () and Weiqing Wang ()
Additional contact information
Aibo Gao: Shanghai Jiao Tong University School of Medicine
Junlei Su: Shanghai Jiao Tong University School of Medicine
Ruixin Liu: Shanghai Jiao Tong University School of Medicine
Shaoqian Zhao: Shanghai Jiao Tong University School of Medicine
Wen Li: Shanghai Jiao Tong University School of Medicine
Xiaoqiang Xu: Aimigene Institute
Danjie Li: Shanghai Jiao Tong University School of Medicine
Juan Shi: Shanghai Jiao Tong University School of Medicine
Bin Gu: Shanghai Jiao Tong University School of Medicine
Juan Zhang: Shanghai Jiao Tong University School of Medicine
Qi Li: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Xiaolin Wang: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Yifei Zhang: Shanghai Jiao Tong University School of Medicine
Yu Xu: Shanghai Jiao Tong University School of Medicine
Jieli Lu: Shanghai Jiao Tong University School of Medicine
Guang Ning: Shanghai Jiao Tong University School of Medicine
Jie Hong: Shanghai Jiao Tong University School of Medicine
Yufang Bi: Shanghai Jiao Tong University School of Medicine
Weiqiong Gu: Shanghai Jiao Tong University School of Medicine
Jiqiu Wang: Shanghai Jiao Tong University School of Medicine
Weiqing Wang: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.

Date: 2021
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DOI: 10.1038/s41467-021-27187-7

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