The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

Abstract

Background: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?

“…As described in former sections, increased abundance of Veillonellaceae and Veillonella have been associated with higher systemic inflammation, endotoxemia and HE in patients with liver cirrhotics [188,214,216,246]. It is noteworthy in this study that the amount of Veillonella showed strong correlations to multiple bile acid profiles in the feces (e.g., total primary and secondary BAs levels, primary BAs/secondary BAs ratio, and sulfo-conjugates) [246]. Veillonella is also known as a 7α-dehydroxylating bacteria, promoting secondary BA formation in the intestine [253].…”

“…Their study indicated that Enterococcus and Lactobacillus were increased in PSC patients without liver cirrhosis, LT or concomitant IBD [241], although the dysbiosis had been associated with liver cirrhosis [38,98] and IBD [195]. The increase in Fusobacterium, also reported later by Torres et al [246], might be meaningful, when considering its known linking with colorectal cancer in PSC patients [247]. nishiishi et al [248] demonstrated significant increases in Escherichia, Lachnospiraceae and Megasphera in the patients with PSC-IBD compared with controls.…”

“…Its impact on the pathogenesis of PSC should be further evaluated. The authors discussed that unexpectedly low abundance of Veillonella in their PSC-IBD patients could be explained by the earlier stage of disease [246]. As described in former sections, increased abundance of Veillonellaceae and Veillonella have been associated with higher systemic inflammation, endotoxemia and HE in patients with liver cirrhotics [188,214,216,246].…”

“…Recently Torres et al [246] reported increased abundance of fecal Ruminococcus and Fusobacterium in 15 Portuguese PSC-IBD patients compared with IBD patients, while Dorea, Veillonella, Lachnospira, Blautia, and Roseburia were less abundant. Although the authors explained their inconsistent results on the abundance of Blautia in the mucosa and feces by the dissociation between the mucosal microbiota and fecal microbiota [246].…”

“…The authors discussed that unexpectedly low abundance of Veillonella in their PSC-IBD patients could be explained by the earlier stage of disease [246]. As described in former sections, increased abundance of Veillonellaceae and Veillonella have been associated with higher systemic inflammation, endotoxemia and HE in patients with liver cirrhotics [188,214,216,246]. It is noteworthy in this study that the amount of Veillonella showed strong correlations to multiple bile acid profiles in the feces (e.g., total primary and secondary BAs levels, primary BAs/secondary BAs ratio, and sulfo-conjugates) [246].…”