Response to letter to the editor: “GLP-1RAs for pouchitis in obesity: what the current study does not tell us”

To the Editors, We thank Dr Zhu and colleagues for their thoughtful interest in our study and are pleased that it has prompted further discussion.1 We reported that the use of glucagon-like peptide-1 receptor agonist (GLP-1RA) was associated with a lower risk of recurrent pouchitis in patients with obesity and an ileal pouch–anal anastomosis (IPAA) with prior pouchitis. The authors raise 3 points, concerning mechanism, pouch motility, and nutrition, which we are pleased to address.2 First, we agree with Zhu et al. that we did not provide direct microbial evidence for the protective effect. We did, however, propose a biologically grounded rationale. Preclinical models show that GLP-1 signaling suppresses nuclear factor-κB activation and reduces tumor necrosis factor-α and interleukin-6.3,4 In addition, the peripouch fat depot is independently associated with chronic pouchitis, and its reduction may lessen local inflammatory and mechanical stress.5 Because the TriNetX database contains neither endoscopic nor microbiome data, these mechanisms remain hypotheses that we could not test directly. We agree that pouch aspirate sequencing with short-chain fatty acid and bile acid profiling would be valuable in future studies.