Clinical, microbiological and metabolic features of patients with Crohn’s disease and intestinal failure

Abstract

The pathogenesis of inflammatory bowel disease (IBD) involves the interaction between an individual’s genes, gut microbiota and environmental factors. The Crohn’s disease (CD) microbiome is characterised by a reduction in Firmicutes and an increase in Proteobacteria. The CD metabonome consistently shows a reduction in secondary bile acids (SBAs) and an increase in stool and serum primary bile acids (PBAs). Very few studies have examined the multiomic profile in patients with Crohn’s disease-intestinal failure (CD-IF).

I present two retrospective case-control studies and one prospective multiomics study. I identified the following risk factors for the development of IF in patients with CD: female gender, ileocolonic involvement, penetrating disease and non-exposure to biologic medications. Patients with CD-IF are twice as likely to be in remission compared to patients with CD (without IF) and the strongest factor associated with active disease, was the presence of a surgical anastomosis to colon in continuity compared to those with an end enterostomy.

For the multiomics study, stool, serum and urine samples from CD-IF patients were analysed. 16s rRNA sequencing demonstrated an expansion of aerotolerant and facultative anaerobic microorganisms, with a decrease in obligate anaerobes; the CD-IF gut luminal environment has a higher oxygen content. Metabonomic profiling showed a higher serum and faecal cholic acid and chenodeoxycholic acid in active disease compared to remission; this is in keeping with the theory that loss of bowel length leads to loss of farnesoid X receptor (FXR) and Fibroblast growth factor 19 (FGF19) and an increase in hepatic synthesis of PBAs. Expectedly, an almost absence of serum SBAs was observed in CD-IF. Multiomics changes seen with active disease could be a cause or a consequence of disease activity, or secondary to the anatomic changes or changes in diet and parenteral nutrition.