Multi‐omics reveals different signatures of obesity‐prone and obesity‐resistant mice
Congcong Wang,
Jinhua Lin,
Meng Duan,
Jialing He,
Simayi Halizere,
Ningxin Chen,
Xinyu Chen,
Ye Jiao,
Wei He,
Kenneth A. Dyar,
Fei Yang,
Shankuan Zhu
Affiliations
Congcong Wang
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Jinhua Lin
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Meng Duan
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Jialing He
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Simayi Halizere
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Ningxin Chen
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Xinyu Chen
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Ye Jiao
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Wei He
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Kenneth A. Dyar
Metabolic Physiology, Institute for Diabetes and Cancer, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg Germany
Fei Yang
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Shankuan Zhu
Department of Nutrition and Food Hygiene, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou China
Abstract Obesity‐prone (OP) and obesity‐resistant (OR) individuals demonstrate significant metabolic differences, potentially influenced by variations in the gut microbiome. However, the influence of host–microbiota interactions on obesity susceptibility remains unknown. We performed an integrative multi‐omics approach to explore microbial, metabolic, and genetic differences in high‐fat diet (HFD)‐fed OP and OR mice, with additional analyses of gut microbiota variations in humans. In OP mice, the dynamic gut microbiota was characterized by a stable presence of Longibaculum, while Kineothrix predominated in OR mice. We termed both as keystone bacteria. Beyond these, eight dominant bacterial genera were significantly associated with bile acid metabolites and amino acids. Three of these genera were also identified in OR humans and showed positive correlations with genes that may support intestinal barrier function. We identified 22 specific amino acid profiles as potential biomarkers for obesity susceptibility, along with significantly increased levels of ten non‐12‐OH bile acids in fecal of OR mice. In vivo, mouse experiments demonstrated that ursodeoxycholic and hyodeoxycholic acids could reduce HFD‐induced obesity. Additionally, the colon of OP mice displayed a higher presence of inflammatory cells. These findings suggest that host–microbiota interactions may contribute to phenotypic differences between OP and OR. Our study offers insights into crucial intestinal markers associated with obesity, providing a valuable resource for advancing the understanding of obesity‐prone and obesity‐resistant phenotypes.
