Compositional and functional differences of gut microbiome and metabolome inform pathogenesis of cholestatic liver disease
= 278, respectively) were analyzed by shotgun sequencing and ultrahigh-resolution mass spectrometry. Comparisons were conducted with covariate-adjusted linear models. The gut microbiomes of patients with PSC and PBC were characterized by reduced diversity and increased abundance of pathobionts and virulence factors, coupled with altered microbial metabolism, including a reduction of short-chain fatty acids and B-vitamins. Untargeted stool metabolomics supported these results. Patients were stratified into groups using their microbial signatures, and each group had distinct patterns of microbiome-related changes. Cox regression analysis revealed that pathogenic microbial species were predictive of hepatic decompensation, whereas beneficial species had a protective effect. Based on previous groundwork and our new results, microbiome-based interventions such as probiotics, short-chain fatty acid supplementation, and phage therapy represent promising therapeutic options for cholestatic liver diseases.
Authors
- Elizabeth J. Carey (ORCID: https://orcid.org/0000-0001-8580-2122)
- Nicholas F. LaRusso (ORCID: https://orcid.org/0000-0003-3266-0831)
- Sami Teeny (ORCID: https://orcid.org/0009-0000-1271-2492)
- John E. Eaton (ORCID: https://orcid.org/0000-0002-8029-4947)
- Bryan M. McCauley (ORCID: https://orcid.org/0000-0003-4014-2663)
- Arjun P. Athreya (ORCID: https://orcid.org/0000-0001-9764-1768)
- Konstantinos N. Lazaridis (ORCID: https://orcid.org/0000-0002-0437-681X)
- Caroline W. Grant (ORCID: https://orcid.org/0000-0001-9342-2138)
- Young‐Mi Go (ORCID: https://orcid.org/0000-0003-3353-0844)
- Stephen Johnson
- Elizabeth J. Atkinson (ORCID: https://orcid.org/0000-0002-1191-3775)
- Erik M. Schlicht
- Purna Kashyap (ORCID: https://orcid.org/0000-0002-2851-2388)
- Gary W. Miller (ORCID: https://orcid.org/0000-0001-8984-1284)
- Marios Nikolaidis (ORCID: https://orcid.org/0000-0002-3902-9367)
- André Franke (ORCID: https://orcid.org/0000-0003-1530-5811)
- Jackie K. Bianchi
- Chang Hu (ORCID: https://orcid.org/0009-0002-8963-8803)
- Brian D. Juran
- T H Karlsen
- J E R Hov
- Ahmad H. Ali
- Ruben A. Mars
- Christoph Schramm
- ViLinh Tran
- Gregory J. Gores
- Grigorios D. Amoutzias
- Venetia Tragaki
- Dean P. Jones
Institutions
- Oslo University Hospital (NO)
- Mayo Clinic (US)
- University of Thessaly (GR)
- University of Illinois Urbana-Champaign (US)
- Universität Hamburg (DE)
- University of Oslo (NO)
- WinnMed (US)
- Center for Innovative Public Health Research (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Pulmonary and Allergy Associates (US)
- Mayo Clinic in Arizona (US)
- University of Missouri (US)
Publication Details
- Journal
- Gut Microbes
- Published
- 2026-04-13
- DOI
- https://doi.org/10.1080/19490976.2026.2655793
- Primary Topic
- Liver Diseases and Immunity
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health