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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microorganisms in Vertebrate Digestive Systems

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1636007

Integrated Analysis of Fecal Microbiota and Metabolomics Reveals Unique Characteristics of Asymptomatic and Classic Celiac Disease

Provisionally accepted
Shanxia  YaoShanxia Yao1Shenglong  xueShenglong xue1Na  liNa li2Tian  ShiTian Shi2Yan  FengYan Feng2Ayinuer  MaimaitireyimuAyinuer Maimaitireyimu2Munila  maimaitiMunila maimaiti2Halina  HalikeHalina Halike2Feng  GaoFeng Gao2*
  • 1新疆大学, 乌鲁木齐, China
  • 2People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China

The final, formatted version of the article will be published soon.

Celiac Disease (CeD) is a clinical manifestation-based autoimmune small intestinal disorder with subtypes (typical, atypical, asymptomatic). While classic CeD development is linked to microbes/metabolites, their relationships with other subtypes remain unclear. We conducted 16S rDNA sequencing on fecal samples from 14 asymptomatic CeD (SCeD) patients and integrated this data with our team's prior sequencing data of 30 classic CeD (CDF) patients and 30 healthy controls (CDFH). 16S rDNA results showed: Compared to CDFH, SCeD had lower abundances of Bacteroides, Alistipes, CAG-352 and higher abundances of Blautia, Collinsella, Dorea, Mediterraneibacter, Gemmiger; a random forest model based on 8 differential microbes distinguished SCeD from CDFH (AUC=0.97). Compared to CDF, SCeD had lower Bacteroides and higher Faecalibacterium, Blautia, Collinsella, Agathobacter — suggesting Bacteroides may relate to CeD symptoms, while Faecalibacterium and Agathobacter may alleviate symptoms. Metabolomic analysis identified differential metabolites between SCeD and CDFH (enriched in "Steroid Hormone Biosynthesis", "Primary Bile Acid Biosynthesis", "Tryptophan Metabolism" via KEGG) and between SCeD and CDF (enriched in "Tryptophan Metabolism", "Biosynthesis of Plant Secondary Metabolites", "Degradation of Flavonoids"). Spearman analysis showed correlations between differential microbes and metabolites.In conclusion, different CeD subtypes may involve a "host-microbe-metabolite" trinity network: A random forest model built with SCeD-CDFH differential microbes/metabolites is a high-efficacy SCeD diagnostic tool; modulating these microbes/metabolites could be a new entry point for CeD mechanism research and adjunctive therapy.

Keywords: asymptomatic celiac disease, Classic celiac disease, microbiota, Metabolites, Diagnosticmarkers

Received: 04 Jul 2025; Accepted: 23 Oct 2025.

Copyright: © 2025 Yao, xue, li, Shi, Feng, Maimaitireyimu, maimaiti, Halike and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Feng Gao, xjgf@sina.com

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