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Functional and metabolic alterations of gut microbiota in children with new-onset type 1 diabetes

Yuan Xiaoxiao,Wang Ruirui,Han Bing,Sun ChengJun,Chen Ruimin,Wei Haiyan,Chen Linqi,Du Hongwei,Li Guimei,Yang Yu,Chen Xiaojuan,Cui Lanwei,Xu Zhenran,Fu Junfen,Wu Jin,Gu Wei,Chen Zhihong,Fang Xin,Yang Hongxiu,Su Zhe,Wu Jing,Li Qiuyue,Zhang Miaoying,Zhou Yufeng,Zhang Lei,Ji Guang,Luo Feihong

Gut dysbiosis has been linked to type 1 diabetes (T1D); however, microbial capacity in T1D remains unclear. Here, we integratively profiled gut microbial functional and metabolic alterations in children with new-onset T1D in independent cohorts and investigated the underlying mechanisms. In T1D, the microbiota was characterized by decreased butyrate production and bile acid metabolism and increased lipopolysaccharide biosynthesis at the species, gene, and metabolite levels. The combination of 18 bacterial species and fecal metabolites provided excellently discriminatory power for T1D. Gut microbiota from children with T1D induced elevated fasting glucose levels and declined insulin sensitivity in antibiotic-treated mice. In streptozotocin-induced T1D mice, butyrate and lipopolysaccharide exerted protective and destructive effects on islet structure and function, respectively. Lipopolysaccharide aggravated the pancreatic inflammatory response, while butyrate activated Insulin1 and Insulin2 gene expression. Our study revealed perturbed microbial functional and metabolic traits in T1D, providing potential avenues for microbiome-based prevention and intervention for T1D.