Associations of fecal bile acids, diet, and intestinal microbes with markers of disease progression in primary sclerosing cholangitis disease
Primary Sclerosing Cholangitis (PSC) disease progression is variable and associated with changes in bile acids (BA) and intestinal dysbiosis. The objective of this study was to elucidate relationships between diet, intestinal microbes, and fecal bile acids with markers of PSC progression. Stool and blood was collected from patients with early-stage, large duct PSC for measurements of bile acids (BA; LC-MS/MS) and fecal 16S rRNA DNA sequencing. Dietary intake of alcohol, fats, protein, and fiber was estimated from food frequency questionnaires. Healthy controls (HC) included individuals who had participated in a diet supplement clinical trial and had received placebo. A total of 24 patients with PSC (58.3% male, 70.8% with IBD) with a median age 53.8 years alkaline phosphatase 174.5 IU , and total bilirubin 17.1 micromol/L, micromol/L, and 10 HC were enrolled. Unconjugated fecal BA  was lower in PSC than HC. No other differences in fecal BA were found. Among patients with PSC, fDCA, but no other BA, was negatively associated with TB after adjusting for IBD status and UDCA use. No fecal BA were associated with serum alkaline phosphatase. Surprisingly, fDCA was associated with greater serum C4. Serum FGF19 was not associated with fDCA or C4. Alcohol intake, but not intake of fats, protein, or fiber, was associated with higher fDCA levels and lower serum bilirubin. Mic robiotame analysis revealed correlations between fDCA and increasing abundance of Blautia and Lachnoclostridium and decreasing Streptococcus. Blautia also correlated with total fecal BA.