Altered microbiota and bile acid composition in patients with primary sclerosing cholangitis

Background:

Recent studies revealed that commensal microbiota is a crucial player in noncommunicable chronic inflammatory diseases. However, in primary sclerosing cholangitis (PSC), an autoimmune cholestatic liver disease of unknown origin, few data exist on the biliary microbiota, bile acid (BA) diversity and their interplay.

Methods:

Oral, duodenal mucosa and duodenal fluid as well as bile samples were collected prospectively from 36 patients with PSC and 22 diseased control subjects undergoing endoscopic retrograde cholangiography (ERC). Among others, exclusion criteria were antibiotic treatment in the past 6 months and ERC in the past 12 months before study inclusion. Microbiota of the bile and the upper digestive tract was profiled by sequencing of the 16S rRNA DNA. Biliary BA were measured by high-performance liquid chromatography mass spectrometry. Microbiota was analysed by community ecology methods. Associations between bacterial abundance and BA expression was explored using sparse partial least squares regression.

Results:

Upper digestive and biliary microbiota profiles differed between PSC patients and controls (permutational analysis of variance; p < 0.01, respectively). The biliary microbiota communities showed the strongest differences between PSC patients and controls. Biliary microbiota in PSC was characterised by an altered composition (“dysbiosis”) with decreased diversity (Shannon diversity index; p = 0.022) and increased abundance of known human pathogens, such as the genera Enterococcus (log2 fold change [log2FC]= 8.75, q< 0.001), Citrobacter (log2FC = 8.46, q< 0.001) and Klebsiella (log2FC = 3.35, q = 0.002). Several proinflammatory bacterial pathways were enriched in PSC. The total BA pool was decreased in PSC patients. Expression of the toxic and potentially tumour promoting secondary bile acids deoxycholic acid and lithocholic acid showed a strong positive association with Enterococcus abundance in PSC.

Conclusion:

Patients with PSC display an altered biliary microbiota and BA composition. Bile microbiota dysbiosis might contribute to an altered and presumably more toxic biliary BA pool in PSC.