The Microbiome in Primary Sclerosing Cholangitis: Current Evidence and Potential Concepts

Abstract

The close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease has inspired hypothetical models in which gut bacteria or bacterial products are key players in PSC pathogenesis. Several studies using high-throughput sequencing technology to characterize the gut microbiota in PSC have been published over the past years. They all report reduced diversity and significant shifts in the overall composition of the gut microbiota. However, it remains unclear as to whether the observed changes are primary or secondary to PSC development and further studies are needed to assess the biological implications of the findings. In the present article, we review the published data in perspective of similar studies in other diseases. We discuss aspects of methodology and study design that are relevant to interpretation of the data. Furthermore, we propose that interpretation and further assessments of findings are structured into conceptual compartments, and elaborate three such possible concepts relating to immune function (the "immunobiome"), host metabolism (the "endobiome"), and dietary and xenobiotic factors (the "xenobiome") in PSC.

Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis

“…Interestingly, colectomy prior to PSC diagnosis is associated with decreased risk for liver transplantation or death 35. While positive family history and male gender are well-established risk factors for PSC,36 accumulating evidence points to a role of gut microbiota in disease pathogenesis 37. In PSC, several cross-sectional studies demonstrated a reduced gut alpha diversity and significant alterations in the overall microbiota composition compared with healthy controls 17–19.…”

Studying the Exposome to Understand the Environmental Determinants of Complex Liver Diseases

“…Smoking is negatively associated with PSC in patients with concomitant inflammatory bowel disease . Meanwhile, evaluation of the microbiome has generally demonstrated overall inconsistent results except for evidence of reduced alpha diversity in the majority of studies …”

Circulating markers of gut barrier function associated with disease severity in primary sclerosing cholangitis

“…The close relationship with IBD is the basis of several important hypotheses of PSC pathogenesis. Recent studies have identified an altered gut microbiota in PSC patients, both in stool and the mucosa . It has previously been hypothesized that leakage of bacterial products across an impaired mucosal barrier in the gut could contribute to the disease.…”

“…Recent studies have identified an altered gut microbiota in PSC patients, both in stool and the mucosa. 4 It has previously been hypothesized that leakage of bacterial products across an impaired mucosal barrier in the gut could contribute to the disease. The liver is continuously exposed to a large variety of substances, including nutrients, gut bacteria and bacterial products originating from the gut via the portal circulation.…”