Journal Article

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

Pfeffer-Gik, Tamar, Snir, Yifat, Sharar Fischler, Tali, Banai Eran, Hagar, Reshef, Leah, Godny, Lihi, Dotan, Iris, Pauker, Maor H., Freidenberg, Adi, Yanai, Henit, Goren, Idan, Rabinowitz, Keren M., Broitman, Yelena, Ollech, Jacob E., Gophna, Uri, Avni-Biron, Irit

2025

Overview

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.

• Publisher: Wolters Kluwer,Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins,American College of Gastroenterology
• Subject: Adult / Antibiotics / Biological Products - pharmacology / Biological Products - therapeutic use / Biomarkers / Chronic illnesses / Clinical outcomes / Cohort analysis / Crohn Disease - diagnosis / Crohn Disease - drug therapy / Crohn Disease - immunology / Crohn Disease - microbiology / Crohn's disease / Dysbiosis - diagnosis / Dysbiosis - drug therapy / Dysbiosis - immunology / Dysbiosis - microbiology / Feces / Feces - microbiology / Female / Follow-Up Studies / Gastrointestinal Microbiome - drug effects / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - immunology / Gut microbiota / Humans / Inflammatory Bowel Disease / Longitudinal Studies / Male / Metabolism / Middle Aged / Patients / Prospective Studies / Remission (Medicine) / Remission Induction - methods / Review boards / RNA, Ribosomal, 16S - genetics / Severity of Illness Index / Steroids / Treatment Outcome / Tumor necrosis factor-TNF / Veganism / Young Adult