PT - JOURNAL ARTICLE AU - Haifeng Sun AU - Peng Wang AU - Gulisudumu Maitiabula AU - Li Zhang AU - Jianbo Yang AU - Yupeng Zhang AU - Xuejin Gao AU - Jieshou Li AU - Bin Xue AU - Chao-Jun Li AU - Xinying Wang TI - Total parenteral nutrition drives glucose metabolism disorders by modulating gut microbiota and its metabolites AID - 10.1101/2021.10.26.466009 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.10.26.466009 4099 - http://biorxiv.org/content/early/2021/10/27/2021.10.26.466009.short 4100 - http://biorxiv.org/content/early/2021/10/27/2021.10.26.466009.full AB - The occurrence of glucose metabolism disorders is a potentially fatal complication of total parenteral nutrition (TPN). However, the mechanisms of TPN-associated glucose metabolism disorders remain unclarified. Given that the glucose metabolism was related to gut microbiome and TPN could induce the gut microbiota dysbiosis, we hypothesized that gut microbiota and its metabolites played the important roles in TPN-associated glucose metabolism disorders. By performing a cohort study of 256 type 2 IF patients given PN, we found that H-PN (PN>80%) patients exhibited insulin resistance and a higher risk of complications. Then, TPN and microbiome transfer mice model showed that TPN promoted glucose metabolism disorders by inducing gut microbiota dysbiosis; 16S rRNA sequencing demonstrated that the abundance of Lactobacillaceae was decreased in mice model and negatively correlated with HOMA-IR and lipopolysaccharide level in TPN patients. Untargeted metabolomics found that indole-3-acetic acid (IAA) was decreased in TPN mice, and the serum level was also decreased in H-PN patients. Furthermore, GLP-1 secretion regulated by IAA and aryl hydrocarbon receptor was reduced in TPN mice and patients; IAA or liraglutide completely prevented glucose metabolism disorders in TPN mice. In conclusion, TPN drives glucose metabolism disorders by inducing alteration of gut microbiota and its metabolites.Competing Interest StatementThe authors have declared no competing interest.