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The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls
Open accessAbstract
Objective: Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease. Design: We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p<0.05, Q FDR <0.20) in both panels were reported, followed by a combined comparison of all samples against UC. Results: Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p<0.0001), and a different global microbial composition compared with both HC (p<0.001) and UC (N=36, p<0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, the Veillonella genus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis, Veillonella abundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78. Conclusions: Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC.
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Recent studies support an association between changes in the microbiome and the progression of cholestatic liver disease in patients.
“Recent studies have further supported the association between changes in the microbiome and the progression of cholestatic liver disease in patients9–14.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [9]
Some changes found during human disease are replicated in mice after BDL, as we observed a significant enrichment of Akkermansia, in line with the observations in the study by Kummen and colleagues.
“More importantly, some of the changes found during human disease are replicated in mice after BDL as we observed a significant enrichment of Akkermansia, in line with the observations in the study by Kummen and colleagues9.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [9]
Changes at genera level in cholestatic patients differ among studies and include enrichment in Veillonella, Akkermansia, Ruminococcaceae (undefined genus) and Clostridium and decrease in Prevotella.
“The changes described at genera level differ among studies9–12 and include the enrichment in Veillonella, Akkermansia, Ruminococcaceae (undefined genus) and Clostridium9 and the decrease in Prevotella10, overall supporting the association between changes in the microbiome and cholestatic disease.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [9]
Recent studies described that cholestatic patients with PSC have an overall less diverse microbiome composition.
“Recent studies described that cholestatic patients with PSC have an overall less diverse microbiome composition.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [9]
Clostridium is increased in PSC patients and PBC patients.
“which is in agreement with what was found in PSC patients9 as well as in PBC patients13.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [9]
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Th17 cell frequency is associated with low bone mass in primary sclerosing cholangitis
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The Human Gut Microbiome in Liver Diseases
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“Four of these taxa (Fusobacterium, Scardovia, Veillonella and Rothia dentocariosa) are known members of the oral microbiota, are not usually found in the gut and have been reported in IBD, colorectal cancer, and liver diseases [156].”
BackgroundImmunobiology of primary sclerosing cholangitis
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Metadata
- Authors
- Kummen, M., Holm, K., Anmarkrud, J. A., Nygård, S., Vesterhus, M., Høivik, M. L., Trøseid, M., Marschall, H.-U., Schrumpf, E., Moum, B., Røsjø, H., Aukrust, P., Karlsen, T. H., & Hov, J. R.
- Affiliations
- Oslo University Hospital (NO)
- University of Gothenburg (SE)
- University of Oslo (NO)
- Corresponding author
- Hov, Johannes R
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2016-02-17
- Volume
- 66
- Issue
- 4
- Pages
- 611-619
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2303705264
- Cited by
- 426
- References
- 60
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 44 · 2023: 49 · 2022: 39 · 2021: 56 · 2020: 47 · 2019: 46 · 2018: 33 · 2017: 30 · 2016: 19
- FWCI
- 22.17
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- primary sclerosing cholangitis, gut microbiota, ulcerative colitis, Veillonella, bacterial diversity, microbial signatures, inflammatory bowel disease, biliary tract diseases, stool microbiome, diagnostic biomarkers
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Aged, 80 and over, Colitis, Ulcerative, Cross-Sectional Studies, Feces, Female, Humans, Male, Middle Aged, Prospective Studies, RNA, Ribosomal, 16S, ROC Curve, Severity of Illness Index, Veillonella, Cholangitis, Sclerosing, Case-Control Studies, Area Under Curve, Young Adult, Healthy Volunteers
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