Short bowel syndrome (SBS)‐associated alterations within the gut‐liver axis evolve early and persist long‐term in the piglet model of short bowel syndrome

Prue M Pereira‐Fantini, Julie E Bines, Susan Lapthorne, Fiona Fouhy, Michelle Scurr, Paul D Cotter, Cormac GM Gahan, Susan A Joyce

Short bowel syndrome (SBS) is primarily characterised by malabsorption and malnutrition resulting from loss of intestinal absorptive area following massive small bowel resection (SBR). Bile acids and the gut microbiota are functionally-linked within the gut-liver axis, however SBS-associated disturbances within the gut-liver axis remain largely unexplored. The aim of this study was to characterize the evolution of bile acid alterations within the gut-liver axis at both short- and long-term time points and to relate these changes to alterations in colonic bacterial composition. Four week-old piglets were assigned to 75% small bowel resection (SBR), sham operation or non-operation control (NOC) groups. High throughput sequencing was employed to determine bacterial abundance in colonic content and ultra-performance liquid chromatography used to determine the bile acid concentration of gall bladder, portal serum and faecal samples. Bile acid complexity and relative abundance are altered in the SBS piglet model at two weeks post-SBR, and these changes persisted at six weeks post-SBR. Our examination of the microbial profile revealed an early and persistent loss in bacteria belonging to the Clostridiales order. This study provides evidence of an early and persistent disturbance of the bile acid profile throughout the entero-hepatic circulation with an increase in the proportion of primary bile acids and a decrease in secondary bile acids following small bowel resection. These changes were associated with a loss of bacteria belonging to the Clostridiales order consistent with a disturbance in the bile-microbial axis following SBR.