Targeted metabolomics reveals bioactive inflammatory mediators from gut into blood circulation in children with NAFLD.

Journal: NPJ biofilms and microbiomes
Published Date: Jul 1, 2025

Abstract

Altered gut metabolites are important for the inflammatory progression in children with NAFLD. Fecal and plasma samples were collected from 145 subjects including 53 non-alcoholic fatty liver (NAFL), 39 nonalcoholic steatohepatitis (NASH) and 53 obese controls. We performed G350 targeted integrative metabolomics using high performance liquid chromatography mass spectrometry for fecal and plasma analysis of NAFL, NASH, and obese children. We found 9 metabolites involved in metabolic reprogramming of inflammation in NAFLD, such as lipid, carbohydrate, amino acid metabolism, and TCA cycle pathway. Moreover, 7 inflammation-related metabolites could discriminate NAFLD severity by machine learning model. This study identified three novel elevated inflammatory pathogenic metabolites and the relationship between increased inflammation, may be involved in TLR5/MYD88/NFκB pathway. These findings reveal that specific inflammatory metabolites entering the blood circulation from the gut are associated with disease severity and inflammatory pathogenesis in children with NAFLD.

Authors

  • Miyang Luo
    International Initiative on Spatial Lifecourse Epidemiology (ISLE), the Netherlands; Saw Swee Hock School of Public Health, National University of Singapore, 117549, Singapore.
  • Jiayou Luo
  • Atipatsa C Kaminga
    Department of Epidemiology and Health Statistics, Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China.
  • Jia Wei
    Department of Thyroid Surgery, The First Hospital of Jilin University Changchun 130021 P. R. China mengxiany@mail.jlu.edu.cn.
  • Wen Dai
    School of Kinesiology, Shanghai University of Sport Shanghai, China.
  • Yan Zhong
  • Ningan Xu
    Institute of Children Health, Hunan Children's Hospital, Changsha, Hunan, China.
  • Xiongwei Li
    Center for Disease Control and Prevention of Ningxiang, Changsha, Hunan, China.
  • Haixiang Zhou
    Center for Disease Control and Prevention of Ningxiang, Changsha, Hunan, China.
  • Xiongfeng Pan
    Pediatrics Research Institute of Hunan Province, Hunan Children's Hospital, Changsha, Hunan, China.

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