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Altered intestinal microbiota prevalent in PSC patients

Patients with primary sclerosing cholangitis have altered intestinal microbiota, according to new findings published in Gut, suggesting microbiota could be used in the future as a biomarker for the treatment and prevention of primary sclerosing cholangitis.

“In the future, gut bacteria may be used to help identify [primary sclerosing cholangitis] patients with a more or less aggressive disease, or patients that may benefit from microbiota-based therapies, such as fecal microbiota transplantation or targeted pre- and probiotics,” Séverine Vermeire, MD, PhD, professor in the Translational Researcher Center for Gastrointestinal Disorders, University of Leuven, Belgium, said in a press release.

Séverine Vermeire

Vermeire and colleagues analyzed stool samples of 147 individuals — 52 with primary sclerosing cholangitis (PSC) and 52 healthy controls — and hypothesized that intestinal microbiota might be altered in patients with PSC and different from healthy controls. Of the patients, 13 had ulcerative colitis and 30 patients had Crohn’s disease. The researchers used 16S rDNA sequencing (Illumina MiSeq) to analyze the fecal DNA.

To confirm findings in the initial analysis, an independent validation cohort of 14 patients with PSC and 14 matched controls were also recruited, sequenced and sampled.

Results showed patients with PSC had overrepresentation of Enterococcus (P = 3.76e-05), Fusobacterium (P = 3.76e-05) and Lactobacillus (P = .0002) genera compared with healthy controls. This was observed in patients with PSC with and without irritable bowel disease and was distinct from IBD. In addition, it was independent of treatment with ursodeoxycholic acid.

“Using massive DNA sequencing, we compared the gut bacteria in patients with PSC and in healthy people. Based on the differences found, we could develop a signature to diagnose PSC based on gut bacteria,” Jeroen Raes, professor in the department of microbiology and immunology, Laboratory of Molecular Bacteriology, University of Leuven, said in a press release. “Although very promising, our findings now need to be confirmed before they can be used in clinical practice.”

For the validation cohort, researchers used a decision tree based on abundances of these three genera, which allowed for reliable classification. More specifically, one operational taxonomic unit belonging to the Enterococcus genus was associated with increased levels of serum alkaline phosphatase (P = .048), a marker of disease severity.

The researchers concluded: “Intestinal microbiota modulation through diet, fecal microbiota transplantation, antibiotics or probiotics may be used in the treatment or prevention of primary sclerosing cholangitis.” – by Melinda Stevens

Disclosure: Vermeire reports receiving grants from AbbVie, MSD, Takeda, Pfizer, and other financial relationships with Genentech/Roche, Celgene, Hospira, Mundipharma and Second Genoma for unrelated work. Raes reports receiving fees from GlaxoSmithKline and Johnson & Johnson/Janssen Pharmaceuticals for unrelated work. Please see the study for all other researchers’ relevant financial disclosures.