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

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

doi:10.1038/s41467-022-33656-4

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

Nat Commun. 2022 Oct 26;13(1):6356. doi: 10.1038/s41467-022-33656-4.

Authors

Xiaoxiao Yuan^#¹, Ruirui Wang^#², Bing Han^{3

4}, ChengJun Sun¹, Ruimin Chen⁵, Haiyan Wei⁶, Linqi Chen⁷, Hongwei Du⁸, Guimei Li⁹, Yu Yang¹⁰, Xiaojuan Chen¹¹, Lanwei Cui¹², Zhenran Xu¹, Junfen Fu¹³, Jin Wu¹⁴, Wei Gu¹⁵, Zhihong Chen¹⁶, Xin Fang¹⁷, Hongxiu Yang¹⁸, Zhe Su¹⁹, Jing Wu¹, Qiuyue Li¹, Miaoying Zhang¹, Yufeng Zhou^{20

21}, Lei Zhang², Guang Ji²², Feihong Luo²³

Affiliations

¹ Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China.
² Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
⁴ Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁵ Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, China.
⁶ Department of Endocrinology and Inherited Metabolic, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
⁷ Children's Hospital of Soochow University, Suzhou, China.
⁸ The First Hospital of Jilin University, Changchun, China.
⁹ Department of Pediatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
¹⁰ The Affiliated Children's Hospital of Nanchang University, Nanchang, China.
¹¹ Department of Endocrinology, Genetics and Metabolism, The Children's Hospital of Shanxi Province, Taiyuan, China.
¹² The First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹³ Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹⁴ Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
¹⁵ Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China.
¹⁶ Department of Neuroendocrinology Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, China.
¹⁷ Fujian Medical University Union Hospital, Fuzhou, China.
¹⁸ Qingdao Women and Children's Hospital, Qingdao, China.
¹⁹ Shenzhen Children's Hospital, Shenzhen, China.
²⁰ Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
²¹ National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China.
²² Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. jg@shutcm.edu.cn.
²³ Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China. luofh@fudan.edu.cn.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Bile Acids and Salts / pharmacology
Butyrates / pharmacology
Diabetes Mellitus, Type 1* / genetics
Gastrointestinal Microbiome* / physiology
Glucose / pharmacology
Lipopolysaccharides / pharmacology
Mice
Streptozocin

Substances

Lipopolysaccharides
Streptozocin
Butyrates
Anti-Bacterial Agents
Bile Acids and Salts
Glucose