Longitudinal dynamics of fecal bile acids in pediatric patients with primary sclerosing cholangitis-ulcerative colitis (PSC-UC) undergoing oral vancomycin therapy (OVT)
Abstract
Background: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease affecting ~1,500 pediatric patients in the US, with most also suffering from ulcerative colitis (PSC-UC), a subtype of chronic inflammatory bowel disease (IBD). Within ten years of diagnosis, many will develop clinical complications (50%) that may require liver transplantation (30%), and these patients have the highest lifetime risk of developing colorectal cancer amongst all IBD. There is currently no effective medical therapy to delay the progression of liver disease or the onset of clinical complications in PSC. Although the etiology of PSC is poorly understood, dysbiosis of the gut microbiome and bacterial-derived metabolites (i.e., bile acids (BAs) have been implicated in PSC. Given the potential for gut dysbiosis in PSC-UC pathogenesis, an empiric treatment with oral vancomycin therapy (OVT) has evolved and has shown some benefit in individual cases and small-uncontrolled case series. It remains unclear, however, how OVT affects the gut microbiome in this clinical setting. We have developed a targeted metabolomics method to study the dynamic response of fecal bile acid concentrations contained in stool specimens collected from pediatric patients with PSC-UC (pPSC-UC) in response to OVT. Longitudinal Study: An IRB-approved prospective longitudinal study (BCM-IRB# H-43759) was conducted at BCM/TCH to examine the fecal and salivary microbiome dynamics in pPSC-UC. The study included the…
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