Integrated Metagenomics and Metabolomics Studies Reveal Core Bacterial Guild Regulating Carbohydrate Metabolism in Pediatric MASLD

作者：Jiating Huang, Xuelian Zhou, H L Wang, Ana Liu, JUNFEN FU, G P Dong, Ying Shen, Wenqing Xiang, Jeffrey Schwimmer, Gang Yu, Jian Huang, Yingping Xiao, Yan Ni · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.05.11.724093 · 研究领域：Gut microbiota and health、Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent pediatric disorder with limited treatment options, primarily due to an incomplete understanding of its molecular drivers. Recent research underscores the role of microbial guilds in metabolic health, but the mechanisms by which dysbiosis driven by core species and co-abundant symbionts disrupt metabolic homeostasis in pediatric MASLD remain unclear. Results Here, we conducted integrated metagenomic and metabolomic analyses on 285 pediatric subjects including MASLD patients, obese and healthy controls. The gut dysbiosis in MASLD was characterized by a depletion of Phocaeicola vulgatus , Bacteroides uniformis , Parabacteroides distasonis , and Bacteroides thetaiotaomicron . Co-abundance network analysis, integrating our cohort with four public datasets, identified these species as core guild members associated with MASLD. Microbial enrichment analysis showed significant disruptions in carbohydrate metabolism, particularly the downregulation of the tricarboxylic acid (TCA) cycle, fructose and sucrose metabolism, and pentose and glucuronate interconversions. P. vulgatus and B. uniformis were identified as dominant species linked to the downregulation of KEGG orthologs (KOs) in these disrupted pathways that were inversely correlated with hepatic injury biomarkers. CAZyme database analysis further emphasized P. vulgatus as the primary contributor to glycoside hydrolases involved in m...