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July 09, 2019
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Gut microbiota changes bile acid composition, affects phenotypic features of IBD

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SAN DIEGO — Higher levels of bile acid-metabolizing microbiota correlated significantly with type and location of disease and mucosal inflammation in patients with inflammatory bowel disease, according to a study presented at Digestive Disease Week.

Another recent study demonstrated that bile acids are overrepresented in patients with Crohn’s disease and ulcerative colitis versus healthy controls, Cristian Hernandez-Rocha, an IBD fellow at Mount Sinai, said during his presentation.

“Given the compacity of the microbiome to transform bile acid and the potential effect of bile acid in the host, we aimed to investigate the association between bile acid-metabolizing microbiota abundance, type of disease, location of the mucosal sample and endoscopic inflammation in [patients with IBD],” he said.

Hernandez-Rocha and colleagues enrolled a total of 262 patients [mean age, 37 years (±14 years); 45% women] with Crohn’s disease (n = 98) or UC/IBD unclassified (n = 113) as well as healthy controls (n = 51). All patients had a previous colonoscopy.

Inflamed mucosa was defined as a segmental simple endoscopic score of more than 2 in patients with Crohn’s disease and as a segmental Mayo endoscopic score of more than 0 in those with UC/IBD unclassified. The researchers gathered biopsy samples of the terminal ileum from 180 patients and the sigmoid colon from 248patients.

The researchers used PICRUSt software to separate DNA for microbial 16s rRNA sequencing and estimate functional content. They also computed the relative amount of Clusters of Orthologous Groups (COG) COG3049, COG1902 and COG1062, which represented bile salt hydrolase, hydroxysteroid dehydrogenase and alphadehydoxylase activity.

The association between COGs, specific diagnosis, biopsy location and inflammation were assessed via a mixed linear regression model.

The researchers identified inflamed mucosa in 19.6% of terminal ileum and 50.5% of sigmoid colon biopsy samples among patients with IBD.

There were more amounts of bile salt hydrolase (COG3049) in sigmoid colon biopsies (P < .05). The abundance of bile salt hydrolase rose independently among patients with IBD compared with healthy controls (P < .05).

In patients with Crohn’s disease, there was a significant elevation in the abundance of hydroxysteroid dehydrogenase (P < .005) compared with healthy controls and those with UC/IBD unclassified. This increase in hydroxysteroid dehydrogenase activity rose independently in the terminal ileum (P < .05).

A greater abundance of alphadehydoxylase was also observed. This increase significantly correlated with inflamed mucosa (P < .05). Biopsy location and diagnosis had no effect on this association.

At the time the biopsy was performed, inflamed mucosa did not appear to be associated with bile salt hydrolase or hydroxysteroid dehydrogenase activity.

“An increase in the different functions [of the gut microbiota] can produce major changes in the bile acid composition and thus produce an effect in the local immune response,” Hernandez-Rocha concluded. “Further analysis, including prospective studies, can better define the effect or the role of the bile acid metabolizing microbiome in intestinal inflammation.” – by Alaina Tedesco

 

Reference:

Hernandez-Rocha C, et al. Abstract 257. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Hernandez-Rocha reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.