PT23. - MICROBIOME PROMOTE SPONTANEOUS GUT ADAPTATIONS IN A PRECLINICAL MODEL OF SHORT BOWEL SYNDROME

PT23.

MICROBIOME PROMOTE SPONTANEOUS GUT ADAPTATIONS IN A PRECLINICAL

MODEL OF SHORT BOWEL SYNDROME

M. Bourgin^1,*, A. Garrigues¹, A. Dumay¹, L. Ribeiro-Parenti ^1,2, H. Shahrour¹, F. Joly^1,3, A. Bado¹, M. Thomas⁴, N. Kapel⁵, M. Le Gall¹, J. Le Behec-Le Bihan^1,6

¹Universite Paris Cite, UMR-S1149, Centre de recherche sur l'inflammation, ²Service de chirurgie Générale Oesogastrique et Bariatrique , AP-HP, Hôpital Bichat -Claude Bernard, Paris, ³Department of gastroenterology, IBD and nutrition Support, , AP-HP, CRMR MarDi, Hôpital Beaujon, Clichy, ⁴ Université Paris-Saclay, UMR1319 - Micalis Institute, Institut National de Recherche pour l'Agriculture, l'alimentation et l'environnement (INRAE), AgroParisTech, Jouy-en-Josas, ⁵ Service de Coprologie fonctionnelle, Paris, France. 6Sorbonne Université, AP-HP, Hôpital de la Pitié-Salpêtrière-Charles Foix, AP-HP, Hôpital de la Pitié-Salpêtrière-Charles Foix,, ⁶Sorbonne Université,, AP-HP, Hôpital de la Pitié-Salpêtrière-Charles Foix, Paris, France

Rationale: The small intestine is the organ responsible for absorbing nutrients. Its extensive resection leads to severe malabsorption and wasting, known as short bowel syndrome (SBS). Spontaneous adaptation following resection leads to intestinal hyperplasia, altered microbiota and gut hormone secretions, and hyperphagia all contributing to recovery of patients with SBS. Most studies do not integrate the microbiome as a driver of these adaptations. Here, we aim to study the effects of microbiome depletion in a rat model of SBS.

Methods: Wistar rats were treated (n=16) or not (n=16) with broad-spectrum antibiotics. Treated (n=8) and untreated (n=8) rats underwent either 80% resection of the small intestine and right colon (SBS) or SHAM-operation (SHAM). Body weight and food intake were measured daily. Faeces, blood, intestine were collected for microbiome, gut hormone and morphometric analyses at 3 weeks.

Results: SBS rats displayed a reduced body weight (BW) gain (P<0,05) and hyperphagia compared to the SHAM rats. Antibiotic-treated SBS rats (SBS-ATB), but not SHAM-ATB, showed a 32.1% reduction in food intake compared to SBS (P<0,001). Whereas the untreated SBS rats partially recovered their BW at 3 weeks, the SBS-ATB rats did not, but exhibited greater heterogeneity in their weight evolution. The intestinal elongation observed in SBS rats after 3 weeks was lower in the SBS-ATB (P<0.001), but no difference in colonic elongation was observed between the groups. Jejunal epithelial hyperplasia was reduced in SBS-ATB compared to SBS rats. The SBS-ATB rats showed an increase in plasma GLP-1 levels. Further analysis is underway to elucidate the mechanisms by which microbiota drive intestinal adaptation.

Conclusion: These preliminary results suggest the gut microbiome may play a role in spontaneous adaptation in SBS, and could harbor new targets for future short bowel syndrome therapie.

Disclosure of Interest: None declared