Inflammatory Bowel Disease Associated with Primary Sclerosing Cholangitis is Associated with an Altered Gut Microbiome and Bile Acid Profile

Abstract

Abstract Background Primary sclerosing cholangitis associated with inflammatory bowel disease [IBD-PSC] carries significant morbidity compared to IBD without PSC. Alterations in microbial composition and bile acid [BA] profiles have been shown to modulate chronic inflammation in IBD, but data in IBD-PSC are scarce. We aimed to assess the differences in gut microbiome composition as well as in the BAs profile and BA-related microbial functions between IBD-PSC and IBD-only. Methods In total, 54 IBD-PSC and 62 IBD-only subjects were enrolled from 2012 to 2021. Baseline samples were collected for faecal DNA shotgun metagenomic sequencing, faecal and serum BA quantification using mass spectrometry, and faecal calprotectin. Liver fibrosis measured by transient elastography was assessed in the IBD-PSC group. Data were analysed using general linear regression models and Spearman rank correlation tests. Results Patients with IBD-PSC had reduced microbial gene richness [p = 0.004] and significant compositional shifts [PERMANOVA: R2 = 0.01, p = 0.03] compared to IBD-only. IBD-PSC was associated with altered microbial composition and function, including decreased abundance of Blautia obeum, increased abundance of Veillonella atypica, Veillonella dispar, and Clostridium scindens [q < 0.05 for all], and increased abundance of microbial genes involved in secondary BA metabolism. Decreased serum sulphated and increased serum conjugated secondary BAs were associated with IBD-PSC and increased liver fibrosis. Conclusion We identified differences in microbial species, functional capacity, and serum BA profiles in IBD-PSC compared with IBD-only. Our findings provide insight into the pathophysiology of IBD associated with PSC and suggest possible targets for modulating the risk and course of IBD in subjects with PSC.