P2617 - Risk of SIBO and Colorectal Cancer Among Non-Obese Patients With Irritable Bowel Syndrome Treated With GLP-1 Agonists

Award: ACG Presidential Poster Award

Sadaf Sadighian, BS¹, Assal Sadighian, BS¹, Allen Seylani, MD¹, Yohannes Haile, MD¹, Arya A. Hamidzad, BS², Allen Luo, MD³
1University of California Riverside School of Medicine, Riverside, CA; 2University of California Riverside, Irvine, CA; 3Keck School of Medicine of the University of Southern California, Moorpark, CA

Introduction: GLP-1 agonists reduce GI motility, including gastric emptying and small intestinal transit. In the colon, they exert bidirectional effects by inhibiting acetylcholine-induced contractions and stimulating peristalsis via activation of CGRP-containing intrinsic neurons, altering gut microbiome composition. Disruption of the migrating motor complex (MMC), which clears bacteria and undigested food from the small intestine, promotes small intestinal bacterial overgrowth (SIBO), dysbiosis, and has been linked to colorectal cancer (CRC) through microbial metabolite accumulation. Impaired motility in IBS may further increase susceptibility to SIBO and may elevate CRC risk via chronic inflammation.

Methods: We conducted a retrospective cohort study using de-identified patient data from the TriNetX platform, which includes comprehensive electronic health records from 143 healthcare systems and over 163 million clinical encounters across 18 countries. The study evaluated the risk of SIBO and CRC in non-obese patients with IBS, comparing those treated with GLP-1 receptor agonists (Cohort A) to those not receiving GLP-1 therapy (Cohort B).

Results: The risk of SIBO in Cohort B (N = 14,315) was 0.66%, compared to 0.49% in Cohort A, a difference that did not reach statistical significance (p = 0.0642; risk ratio, 1.334; 95% CI, 0.982–1.813). In contrast, the risk of CRC was significantly higher in Cohort B (0.51%) compared to Cohort A (0.19 %; N = 14,275) (p < 0.0001; risk ratio, 2.698; 95% CI, 1.736–4.192).

Discussion: Although GLP-1 agonists slow gastrointestinal motility, a known risk factor for SIBO, this study observed a reduced incidence of SIBO among patients with IBS receiving GLP-1 therapy. Several mechanisms may explain this effect. GLP-1 receptor agonists promote regulatory T cell expansion, enhancing immune tolerance and reducing intestinal inflammation, which may preserve barrier integrity. They also modulate the gut microbiota, increasing Akkermansia muciniphila while reducing overall diversity, potentially limiting pathogenic overgrowth. In IBS, where motility is often disordered rather than delayed, GLP-1 therapy may help normalize transit and partially restore MMC-like activity. Additionally, GLP-1–mediated effects on the gut-brain axis may support barrier function. These findings suggest GLP-1 receptor agonists may reduce SIBO risk in IBS and have implications for CRC prevention, warranting further investigation.

Disclosures:
Sadaf Sadighian indicated no relevant financial relationships.
Assal Sadighian indicated no relevant financial relationships.
Allen Seylani indicated no relevant financial relationships.
Yohannes Haile indicated no relevant financial relationships.
Arya Hamidzad indicated no relevant financial relationships.
Allen Luo indicated no relevant financial relationships.

Sadaf Sadighian, BS¹, Assal Sadighian, BS¹, Allen Seylani, MD¹, Yohannes Haile, MD¹, Arya A. Hamidzad, BS², Allen Luo, MD³. P2617 - Risk of SIBO and Colorectal Cancer Among Non-Obese Patients With Irritable Bowel Syndrome Treated With GLP-1 Agonists, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.