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Endocrine, Metabolic & Immune Disorders - Drug Targets

Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Oral Microbiota Associated with Clinical Efficacy of Ustekinumab in Crohn’s Disease

Author(s): Feiyang Xuorcid of author, Rui Xie, Le Heorcid of author, Honggang Wangorcid of author, Yifan Zhuorcid of author, Xiaozhong Yang*orcid of author and Huiming Yu*

Volume 25, Issue 15, 2025

Published on: 13 January, 2025

Page: [1228 - 1239] Pages: 12

DOI: 10.2174/0118715303363951241209060903

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Abstract

Background: Crohn’s Disease (CD) is a chronic inflammatory gastrointestinal disease. Ustekinumab (UST) has been utilized as a therapeutic option for CD patients. However, approximately 40-60% of patients exhibit an inadequate response to UST. Accumulating evidence has confirmed the involvement of oral bacteria in the development of CD. Nevertheless, the relationship between oral microbiota and the efficacy of UST therapy in CD patients has remained unexplored.

Materials and Methods: We recruited 28 healthy individuals and 53 CD patients, 47 of whom completed the entire UST therapy. Oral samples and clinical data were collected. The clinical response and clinical remission were defined based on the CDAI score. Oral samples were analyzed by 16S rRNA gene sequencing. The analysis of sequence data was performed by QIIME and R.

Results: We revealed the oral microbial difference between the Healthy Control (HC) group and the CD group. The enrichment of Fusobacteria, Leptotrichia, Capnocytophaga, and Campylobacter, and the diminution of Haemophilus and Rothia were observed in the CD group. Differences in oral microbiota were also identified among patients with different efficacy of UST. Compared to the response and remission groups, both the non-response and non-remission groups showed significantly higher levels of Fusobacteria and Leptotrichia. Predictive models for clinical response and clinical remission in UST were developed based on oral microbiota, with the Area Under the Curve (AUC) value of 0.944 and 0.930, respectively.

Conclusion: Oral microbiota was relevant to the UST efficacy in patients with CD based on the predictive model. These findings suggest that oral microbiota could serve as a non-invasive prognostic biomarker for UST treatment in CD patients.

Keywords: Crohn's disease, ustekinumab, oral microbiota, 16S rRNA, prognostic biomarker, non-invasive prognostic biomarker.

Graphical Abstract

Graphical abstract illustrating key findings of the study

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