Loss of functional small bowel surface area causes
short bowel syndrome (SBS),
intestinal failure, and
parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to 2 yr to determine which patients will wean from PN. Here, we examined features of gut microbiota and
bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Stool and sera were collected from healthy controls and from patients with SBS (n = 52) with
ileostomy,
jejunostomy, ileocolonic, and jejunocolonic anastomoses fed with PN plus
enteral nutrition or who were exclusively enterally fed. We undertook
16S rRNA gene sequencing, BA profiling, and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS and serum
amino acid analyses. Patients with SBS exhibited altered gut microbiota with reduced gut microbial diversity compared with healthy controls. We observed differences in the microbiomes of patients with SBS with
ileostomy versus
jejunostomy, jejunocolonic versus ileocolonic anastomoses, and PN dependence compared with those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in patients with SBS, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who were weaned from PN were enriched in secondary BAs including
deoxycholic acid and lithocholic aicd. Shifts in gut microbiota and BA metabolites may generate a favorable
luminal environment in select patients with SBS, promoting the ability to wean from PN. Proadaptive microbial species and select BA may provide novel targets for patient-specific
therapies for SBS.NEW & NOTEWORTHY Loss of intestinal surface area causes
short bowel syndrome,
intestinal failure, and
parenteral nutrition dependence. We analyzed the gut microbiota and
bile acid metabolome of a large cohort of
short bowel syndrome adult patients with different postsurgical anatomies. We report a novel analysis of the microbiome of patients with
ileostomy and
jejunostomy. Enrichment of specific microbial and
bile acid species may be associated with the ability to wean from
parenteral nutrition.