P1232 Alterations in microbial composition in patients with newly diagnosed Crohn's disease over a course of one year: data from a prospective longitudinal real-world study

Abstract

Abstract Background Gut microbial composition in Crohn's disease (CD) is variable, changing with specific interventions. We aimed to explore the dynamics in microbial alterations in a cohort of patients with newly diagnosed Crohn's disease (ndCD) over one year. Methods This was a prospective longitudinal real-world study of patients with ndCD1 naïve to therapy who were treated at the physician's discretion. Clinical outcomes at one year were corticosteroid-free clinical remission (CSFR) and biochemical remission ([BR], CRP<1mg/dL and FC<150ug/g). We sequenced paired stool samples from diagnosis and after one year using 16S rRNA gene (V4) and analyzed changes in diversity and dysbiosis indices. A linear mixed-effect model was constructed to identify factors associated with microbial alterations and to identify specific genera that drove the alterations while controlling for confounders. Results Seventy-five patients completed one-year follow-up (49.3% female, median age 27 years [IQR 22-38.5], therapeutic interventions: 45 patients on biological therapies [43 anti-TNF], 26 antibiotics, 10 corticosteroids, 5 underwent surgery, and 59 various nutritional interventions). Rates of CSFR, BR, and conjoined CSFR-BR at one-year post-diagnosis were 64%, 56%, and 45.3%, respectively. We observed an overall significant increase in microbial Shannon diversity (H index), p<0.001, and decreased microbial dysbiosis index (MDI), p=0.007, from baseline to one year. On subgroup analysis, these alterations were significant among patients who achieved the clinical outcomes (all p<0.05) and even more prominent among patients who were on biological therapies (both indices p<0.001). Notably, in the biological therapy subgroup, the microbial composition at diagnosis was less diverse and more dysbiotic than in the non-biological subgroup. In the latter, microbial composition at diagnosis was less disrupted and remained relatively stable over time. Linear mixed model analysis corroborated a positive association between biological therapy and the positive dynamics in microbial indices (H-index, p=0.020 and MDI, p=0.040). Fifteen specific genera drove the microbial alterations over time (Table 1), while alterations in the relative abundance of some genera correlated with changes in clinical biomarkers and clinical indices (Figure 1). Conclusion The microbial composition of this real-world cohort of patients with ndCD improved over the course of one year, which was significant for patients who achieved clinical outcomes and was more prominent for patients requiring biological therapy. In this subgroup, the microbial signature was less diverse and more dysbiotic when diagnosed; this likely led the significant improvement over time. 1 Yanai H,et al. Crohns Colitis 360 2023;5:otad064