ORCID

Abstract

Microbiome perturbations are associated with advanced chronic liver disease (ACLD), but how microorganisms contribute to disease mechanisms is unclear. Here we analysed metagenomes of paired saliva and faecal samples from an ACLD cohort of 86 individuals, plus 2 control groups of 52 healthy individuals and 14 patients with sepsis. We identified highly similar oral and gut bacterial strains, including Veillonella and Streptococcus spp., which increased in absolute abundance in the gut of patients with ACLD compared with controls. These microbial translocators uniquely share a prtC gene encoding a collagenase-like proteinase, and its faecal abundance was a robust ACLD biomarker (area under precision-recall curve = 0.91). A mouse model of hepatic fibrosis inoculated with Veillonella and Streptococcus prtC-encoding patient isolates showed exacerbation of gut barrier impairment and hepatic fibrosis. Furthermore, faecal collagenase activity was increased in patients with ACLD and experimentally confirmed for the prtC gene of translocating Veillonella parvula. These findings establish mechanistic links between oral–gut translocation and ACLD pathobiology.

Publication Date

2026-01-01

Publication Title

Nature Microbiology

Volume

11

Issue

1

Acceptance Date

2025-11-14

Deposit Date

2026-01-28

Funding

We thank all patient participants and healthy volunteers for agreeing to take part in the ‘Gut–Liver Axis in Liver Disease & Transplantation’ study, which was adopted to the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, supporting participant screening and recruitment by the Liver Research and Anaesthetics, Critical Care, Emergency and Trauma Teams at King’s College Hospital NHS Foundation Trust. This study was further supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (426120468 to M. Schirmer) and TUM Innovation Network NextGenDrugs (M. Schirmer) funded under the Excellence Strategy of the Federal Government and the Länder. Further laboratory assays and personnel were also funded by the Foundation for Liver Research (registered charity number: 268211/1134579) and a generous donation from a liver service user to the King’s College Hospital Institute of Liver Studies and Transplantation Charitable Research Fund, King’s College Hospital Charity (registered charity number: 1165593). V.C.P. was supported by the NIHR South London CRN Strategic Greenshoots Funding scheme. The study was also supported by the Science for Life Laboratory (SciLifeLab) and KTH-Royal Institute of Technology and by the Engineering and Physical Sciences Research Council (EPSRC), EP/S001301/1, and Centre for Host–Microbiome Interactions at King’s College London. N.B. and M.M.-G. were supported by the BBSRC Institute Strategic Programme Food Microbiome and Health BB/X011054/1 and its constituent project BBS/E/F/000PR13632 (N.B.) and the BBSRC Core Capability Grant BB/CCG1860/1 at the Quadram Institute Bioscience. We acknowledge support from the National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure, under project number Project SNIC 2020-5-222, SNIC 2019/3-226, SNIC 2020/6-153, SNIC 2021/6-89, SNIC 2021/5-248 and SNIC 2021/6-242. S.L. was supported by GIST Research Institute (GRI) GIST-MIT research collaboration grant by the GIST in 2022, and Basic Science Program (NRF-2021R1C1C1006336) and the Bio and Medical Technology Development Program (2021M3A9G8022959) of the Ministry of Science, ICT, through the National Research Foundation, Korea. We also thank the LifeLinesDEEP participants and the Groningen LifeLines staff for providing and sharing their valuable data. Open access funding provided by Technische Universität München.

First Page

211

Last Page

227

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