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

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. We recruited 28 healthy controls (HC) 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. We revealed the oral microbial difference between the 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 response group and remission group, a significantly higher abundance of Fusobacteria and Leptotrichia was identified both in nonresponse group and nonremission group. Predictive models for clinical response and clinical remission in UST were constructed based on oral microbiota, with the AUC value of 0.944 and 0.930, respectively. Oral microbiota was relevant to the UST efficacy in patients with CD based on the predictive model. It could be considered a non-invasive prognostic biomarker for UST therapy in CD patients.