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

Miyang Luo1, Jiayou Luo1, Atipatsa C Kaminga1

  • 1Department of Epidemiology and Health Statistics, Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China.

PubMed

Insights

Altered gut metabolites drive inflammation in pediatric NAFLD. Specific inflammatory metabolites from the gut correlate with disease severity and pathogenesis in children with non-alcoholic fatty liver disease (NAFLD).

Area of Science:

  • Pediatric Gastroenterology
  • Metabolomics
  • Inflammation Research

Background:

  • Gut metabolites play a crucial role in the inflammatory progression of pediatric non-alcoholic fatty liver disease (NAFLD).
  • Understanding these metabolic alterations is key to deciphering NAFLD pathogenesis in children.

Purpose of the Study:

  • To investigate the role of gut metabolites in the inflammatory pathogenesis of NAFLD in children.
  • To identify specific metabolites associated with NAFLD severity and inflammatory pathways.

Main Methods:

  • Collected fecal and plasma samples from 145 children: 53 with non-alcoholic fatty liver (NAFL), 39 with nonalcoholic steatohepatitis (NASH), and 53 obese controls.
  • Utilized G350 targeted integrative metabolomics via high-performance liquid chromatography-mass spectrometry for comprehensive analysis.
  • Employed machine learning models to discriminate NAFLD severity based on identified metabolites.

Main Results:

  • Identified 9 key metabolites involved in metabolic reprogramming of inflammation in NAFLD, including lipid, carbohydrate, amino acid metabolism, and TCA cycle pathways.
  • Discovered 7 inflammation-related metabolites capable of discriminating NAFLD severity.
  • Characterized three novel elevated inflammatory pathogenic metabolites linked to increased inflammation, potentially involving the TLR5/MYD88/NFκB pathway.

Conclusions:

  • Specific gut-derived inflammatory metabolites are associated with disease severity in pediatric NAFLD.
  • These findings highlight the gut-blood-liver axis in NAFLD pathogenesis and suggest potential therapeutic targets.