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

IF 9.2 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

npj Biofilms and Microbiomes Pub Date : 2025-07-01 DOI:10.1038/s41522-025-00706-w

Miyang Luo, Jiayou Luo, Atipatsa C Kaminga, Jia Wei, Wen Dai, Yan Zhong, Ningan Xu, Xiongwei Li, Haixiang Zhou, Xiongfeng Pan

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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.

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靶向代谢组学揭示NAFLD儿童从肠道进入血液循环的生物活性炎症介质。

改变肠道代谢物是NAFLD儿童炎症进展的重要因素。收集了145名受试者的粪便和血浆样本，包括53名非酒精性脂肪肝（NAFL）， 39名非酒精性脂肪性肝炎（NASH）和53名肥胖对照组。我们使用高效液相色谱质谱法对NAFL、NASH和肥胖儿童的粪便和血浆进行了G350靶向综合代谢组学分析。我们发现9种代谢物参与NAFLD炎症的代谢重编程，如脂质、碳水化合物、氨基酸代谢和TCA循环途径。此外，7种炎症相关代谢物可以通过机器学习模型区分NAFLD的严重程度。本研究鉴定出三种新型炎症致病性代谢物升高与炎症增加的关系，可能参与TLR5/MYD88/NFκB通路。这些发现表明，从肠道进入血液循环的特定炎症代谢物与NAFLD儿童的疾病严重程度和炎症发病机制有关。

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来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.