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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Multi-omics integration reveals oral microbiota-metabolite-immune interactions in recurrent aphthous ulceration

4 affiliations
  1. 1Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine
  2. 2Department of Tuberculosis of Henan Provincial Chest Hospital
  3. 3Department of First Clinical School of Medicine of Henan University of Chinese Medicine
  4. 4Department of Gastroenterology, The First Affiliated Hospital of Henan University of Chinese Medicine

Abstract

Recurrent aphthous ulceration (RAU) is a chronic inflammatory disease of the oral mucosa, but its underlying mechanisms remain unclear. In this study, integrated oral microbiome, serum metabolomics, and immune analyses were performed in 16 RAU patients and 16 healthy controls. 16S rRNA sequencing revealed suggestive compositional shifts in the oral microbiota of RAU patients, with nominal trends toward enrichment of Fusobacterium , Moraxella , and Granulicatella and depletion of Treponema and Lancefieldella . PICRUSt2 analysis indicated functional shifts associated with amino acid metabolism and inflammatory signaling. Untargeted metabolomics identified extensive metabolic remodeling, including altered gamma-glutamylcysteine, eicosapentaenoic acid (EPA), crocetin, pristanic acid, and cysteinyl-containing dipeptides, suggesting disturbances in oxidative stress regulation and inflammatory lipid metabolism. KEGG analysis further demonstrated enrichment of pathways related to cysteine and methionine metabolism, purine metabolism, taurine and hypotaurine metabolism, and primary bile acid biosynthesis. Immune profiling showed significant alterations in CD4 ⁺ T lymphocyte subsets, accompanied by elevated IL-1, IL-6, and TNF-α levels. Integrated correlation analysis revealed strong associations among differential microbial taxa, metabolites, and inflammatory cytokines. Collectively, these findings suggest that coordinated alterations in the oral microbiota, serum metabolites, and immune responses are associated with RAU, providing new insights into the biological features of RAU and potential therapeutic targets for further investigation.

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BibTeX
@article{shao2026multiomics,
  title = {{Multi-omics integration reveals oral microbiota-metabolite-immune interactions in recurrent aphthous ulceration}},
  author = {Cancan Shao and Haojie Wang and Jigao Li and Hongtao Guo and Xiaohong Gong and Ruilin Liu and Huifang He and Mingyi Shao},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fmicb.2026.1889297},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1889297/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Multi-omics integration reveals oral microbiota-metabolite-immune interactions in recurrent aphthous ulceration
AU  - Cancan Shao
AU  - Haojie Wang
AU  - Jigao Li
AU  - Hongtao Guo
AU  - Xiaohong Gong
AU  - Ruilin Liu
AU  - Huifang He
AU  - Mingyi Shao
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1889297
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1889297/full
AB  - Recurrent aphthous ulceration (RAU) is a chronic inflammatory disease of the oral mucosa, but its underlying mechanisms remain unclear. In this study, integrated oral microbiome, serum metabolomics, and immune analyses were performed in 16 RAU patients and 16 healthy controls. 16S rRNA sequencing revealed suggestive compositional shifts in the oral microbiota of RAU patients, with nominal trends toward enrichment of Fusobacterium , Moraxella , and Granulicatella and depletion of Treponema and Lancefieldella . PICRUSt2 analysis indicated functional shifts associated with amino acid metabolism and inflammatory signaling. Untargeted metabolomics identified extensive metabolic remodeling, including altered gamma-glutamylcysteine, eicosapentaenoic acid (EPA), crocetin, pristanic acid, and cysteinyl-containing dipeptides, suggesting disturbances in oxidative stress regulation and inflammatory lipid metabolism. KEGG analysis further demonstrated enrichment of pathways related to cysteine and methionine metabolism, purine metabolism, taurine and hypotaurine metabolism, and primary bile acid biosynthesis. Immune profiling showed significant alterations in CD4 ⁺ T lymphocyte subsets, accompanied by elevated IL-1, IL-6, and TNF-α levels. Integrated correlation analysis revealed strong associations among differential microbial taxa, metabolites, and inflammatory cytokines. Collectively, these findings suggest that coordinated alterations in the oral microbiota, serum metabolites, and immune responses are associated with RAU, providing new insights into the biological features of RAU and potential therapeutic targets for further investigation.
SN  - 1664-302X
ER  -