Baseline Fusobacterium Abundance Predicts Ustekinumab Response in Crohn's Disease: A Prospective Microbiome Cohort Study

The gut microbiota composition in Crohn's disease (CD) patients may influence their response to ustekinumab (UST) therapy. A total of 51 patients with active CD undergoing UST therapy were prospectively enrolled. Clinical activity was evaluated using the Crohn's Disease Activity Index (CDAI), and faecal microbiota were characterised by 16S rRNA sequencing at baseline and week 24. Microbial compositional and functional alterations were assessed, and their correlations with clinical outcomes were examined. At week 24, 46.7% of patients achieved clinical remission and 82.2% achieved clinical response. At baseline, Megamonas (p = 0.009) and Erysipelatoclostridium (p = 0.030) were enriched in the remission group, whereas Fusobacterium (p = 0.016) was more abundant in the non-remission group and correlated positively with C-reactive protein (CRP) but negatively with body mass index (BMI) and serum albumin (ALB). Longitudinal analysis showed that CR patients exhibited increased Clostridium sensu stricto 1 (p = 0.028) and decreased Granulicatella (p = 0.043) after 24 weeks. This study provides real-world evidence supporting the clinical efficacy of UST in Asian patients with active CD. The observed association between elevated baseline Fusobacterium abundance and poorer treatment response suggests a potential microbial influence on therapeutic outcomes. These findings highlight the potential of Fusobacterium as a predictive biomarker for UST response and could provide a rationale for integrating microbiota-modulating strategies to enhance the efficacy of biologics in the future.