Crohn's disease (CD),
ulcerative colitis (UC), and
pouchitis are multifactorial and chronic
inflammatory bowel diseases (IBD).
Pouchitis develops in former UC patients after
proctocolectomy and
ileal-pouch-anal anastomosis and is characterized by
inflammation of the previously normal small intestine comprising the pouch. The extent to which microbial functional alteration (
dysbiosis) in
pouchitis resembles that of CD or UC has not been investigated, and the pathogenesis of
pouchitis remains unknown. We collected 208 fecal metagenomes from 69 patients with a pouch (normal pouch and
pouchitis) and compared them to publicly available metagenomes of patients with CD (n = 88), patients with UC (n = 76), and healthy controls (n = 56). Patients with
pouchitis presented the highest alterations in species, metabolic pathways, and
enzymes, which was correlated with intestinal
inflammation. Ruminococcus gnavus strains encoding
mucin-degrading
glycoside hydrolases were highly enriched in
pouchitis.
Butyrate and secondary
bile acid biosynthesis pathways were decreased in IBD phenotypes and were especially low in
pouchitis. Pathways such as
amino acid biosynthesis and degradation of aromatic compounds and
sugars, encoded by members of the Enterobacteriaceae, were enriched in pouch and CD but not in UC. We developed microbial feature-based classifiers that can distinguish between patients with a normal pouch and
pouchitis and identified species and genes that were predictive of
pouchitis. We propose that the noninflamed pouch is already dysbiotic and microbially is similar to CD. Our study reveals microbial functions that outline the pathogenesis of
pouchitis and suggests bacterial groups and functions that could be targeted for intervention to attenuate small intestinal
inflammation present in
pouchitis and CD.IMPORTANCE
Crohn's disease (CD),
ulcerative colitis (UC), and
pouchitis are chronic inflammatory conditions of the bowel.
Pouchitis develops in former UC patients after
proctocolectomy and
ileal-pouch-anal anastomosis and is characterized by
inflammation of the previously normal small intestine comprising the pouch. The extent to which microbial
dysbiosis in patients with
pouchitis resembles that of CD or UC and the pathogenesis of
pouchitis remains unclear. We investigated the functions in the gut microbiomes of these patients using metagenomics. We found that the noninflamed pouch is already dysbiotic and microbially is similar to CD. Our study reveals microbial functions with a potential role in
pouchitis pathogenesis such as depletion in
butyrate and secondary
bile acid synthesis and enrichment of
amino acid synthesis and degradation of aromatic compounds, encoded by members of the Enterobacteriaceae We developed microbial feature-based classifiers that can distinguish between patients with a normal pouch and
pouchitis and identified species and genes that were predictive of
pouchitis. We suggest species and functions that could be targeted for intervention to attenuate small intestinal
inflammation present in
pouchitis and CD.