PP067 - INTESTINAL MICROBIOTA OF PATIENTS WITH SHORT BOWEL SYNDROME BEFORE AND AFTER TREATMENT WITH GLEPAGLUTIDE, A LONG-ACTING GLP-2 ANALOGUE

PP067

INTESTINAL MICROBIOTA OF PATIENTS WITH SHORT BOWEL SYNDROME BEFORE AND AFTER TREATMENT WITH GLEPAGLUTIDE, A LONG-ACTING GLP-2 ANALOGUE

I. Pinar¹, T. Brach², L. Soldbro³, T. S. Nielsen³, M. K. Hvistendahl³, M. Berner-Hansen^3,4, B. G. Santacruz³, P. B. JEPPESEN^5,*

¹Rigshospitalet, ²CMBIO, Copenhagen, ³Zealand Pharma A/S, Soeborg, ⁴Bispebjerg Hospital, ⁵Department of Intestinal Failure and Liver Diseases, Rigshospitalet, Copenhagen, Denmark

Rationale: Glepaglutide enhances intestinal absorption, which may hypothetically lead to changes in the intestinal microbiota, mainly due to slowing gastrointestinal (GI) transit time. This study evaluated whether the intestinal pro-absorptive effects of glepaglutide were associated with changes in intestinal bacterial load and composition.

Methods: In a single-center, open-label study, 10 patients with short bowel syndrome (SBS) - 8 of 10 with intestinal failure and 8 of 10 without colon-in-continuity (CiC) - were treated with subcutaneous glepaglutide 10 mg once weekly for 24 weeks. Samples were obtained from either stool or ostomy effluent at baseline and after 24 weeks of treatment. Bacterial load was quantified using a spike-in approach and composition was assessed by V3V4 16S rRNA gene sequencing.

Results: 24 weeks of glepaglutide treatment did not significantly alter bacterial load nor composition of the intestinal microbiota of the patients. Bacterial load showed distinct differences between patients with / without a CiC; in patients without a CiC, most samples had values below 10⁹ cells per gram, whereas those with a CiC were within the range observed in healthy individuals (10¹⁰ to 10¹¹ cells per gram feces). Microbiota composition also differed markedly by intestinal anatomy: patients without a CiC had higher abundances of genera mainly associated with upper GI tract, such as Streptococcus, while those with a CiC had greater abundance of genera more commonly found in lower GI tract, including Bifidobacterium.

Conclusion: Treatment with the novel GLP-2 analogue glepaglutide did not result in alterations in intestinal bacterial microbiota in SBS patients. Bacterial load and composition were strongly influenced by intestinal anatomy. This study indicated that changes in glepaglutide-induced intestinal absorption do not seem to be related to changes in the microbiota.

Disclosure of Interest: I. Pinar: None declared, T. Brach: None declared, L. Soldbro: None declared, T. S. Nielsen: None declared, M. K. Hvistendahl: None declared, M. Berner-Hansen: None declared, B. G. Santacruz: None declared, P. B. JEPPESEN Grant / Research Support from: Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast A/S, Ferring Pharmaceuticals, Fresenius Kabi, GlyPharma Therapeutic, Naia Pharmaceuticals, NPS Pharmaceutical, Protara Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectiveBio AG, Zealand Pharma A/S