Microbial Shift Over 1 Year Among Patients With Newly Diagnosed Crohn's Disease Reflects Clinical Trajectory and Exposure to Biologic Treatment: A Prospective Real-World Inception Cohort.

Introduction: The gut microbiome in Crohn's disease (CD) shows variability and conflicting associations with disease activity. We aimed to assess microbial and clinical trajectories in newly diagnosed CD (ndCD) over 1 year.

Methods: This prospective longitudinal inception cohort study followed treatment-naive patients with ndCD for 1 year. The primary outcome was sustained corticosteroid-free clinical remission (CSFR) after 1 year. Paired fecal samples were collected at diagnosis and 1 year later, analyzed using bacterial 16S rRNA gene high-throughput sequencing. Microbial composition changes were compared between baseline and 1-year follow-up and between biologics-treated and conservatively managed patients. Fecal samples from healthy volunteers served as controls.

Results: Seventy-three patients participated; 64.4% achieved sustained CSFR after 1 year. During follow-up, 60.3% had moderate-to-severe disease activity and received biologics (95.5% anti-tumor necrosis factor), whereas 39.7% were managed conservatively. Significant microbial improvements, including increased Shannon diversity and decreased microbial dysbiosis index, were observed only in patients achieving sustained CSFR (both P < 0.001). Biologic-treated patients had more disrupted baseline microbiome composition than conservatively managed ones (Shannon, P = 0.04; microbial dysbiosis index, P = 0.03); they showed significant microbial improvement regardless of clinical success, shifting toward a healthier microbiome profile. Changes in clinical outcomes over 1 year correlated with microbial alterations.

Discussion: Over 1 year, treatment-naive patients with ndCD showed microbial improvements paralleling clinical outcomes, with shifts toward a healthier state. Biologic therapy enhanced microbial profiles, likely due to greater baseline disruption in these patients. These findings suggest that the microbiome is a marker of inflammation and a modifiable factor in CD management.