Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine

Jia Wei; Jiayou Luo; Fei Yang; Xiangling Feng; Ming Zeng; Wen Dai; Xiongfeng Pan; Yue Yang; Yamei Li; Yamei Duan; Xiang Xiao; Ping Ye; Zhenzhen Yao; Yixu Liu; Zhihang Huang; Jiajia Zhang; Yan Zhong; Ningan Xu; Miyang Luo

doi:10.1080/19490976.2024.2351620

Gut Microbes (Dec 2024)

Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine

Jia Wei,
Jiayou Luo,
Fei Yang,
Xiangling Feng,
Ming Zeng,
Wen Dai,
Xiongfeng Pan,
Yue Yang,
Yamei Li,
Yamei Duan,
Xiang Xiao,
Ping Ye,
Zhenzhen Yao,
Yixu Liu,
Zhihang Huang,
Jiajia Zhang,
Yan Zhong,
Ningan Xu,
Miyang Luo

Affiliations

Jia Wei: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Jiayou Luo: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Fei Yang: Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang, Hunan, China
Xiangling Feng: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Ming Zeng: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Wen Dai: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Xiongfeng Pan: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Yue Yang: Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang, Hunan, China
Yamei Li: Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang, Hunan, China
Yamei Duan: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Xiang Xiao: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Ping Ye: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Zhenzhen Yao: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Yixu Liu: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Zhihang Huang: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Jiajia Zhang: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Yan Zhong: Institute of Children Health, Hunan Children’s Hospital, Changsha, Hunan, China
Ningan Xu: Institute of Children Health, Hunan Children’s Hospital, Changsha, Hunan, China
Miyang Luo: Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

DOI: https://doi.org/10.1080/19490976.2024.2351620
Journal volume & issue: Vol. 16, no. 1

Abstract

Read online

ABSTRACTGut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.

Published in Gut Microbes

ISSN: 1949-0976 (Print); 1949-0984 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.tandfonline.com/journals/kgmi

About the journal

Abstract

Keywords