Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation

Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications...

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Main Authors: Laura Buttler, David A. Velázquez-Ramírez, Anja Tiede, Anna M. Conradi, Sabrina Woltemate, Robert Geffers, Birgit Bremer, Vera Spielmann, Julia Kahlhöfer, Anke R.M Kraft, Dirk Schlüter, Heiner Wedemeyer, Markus Cornberg, Christine Falk, Marius Vital, Benjamin Maasoumy
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2487209
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author Laura Buttler
David A. Velázquez-Ramírez
Anja Tiede
Anna M. Conradi
Sabrina Woltemate
Robert Geffers
Birgit Bremer
Vera Spielmann
Julia Kahlhöfer
Anke R.M Kraft
Dirk Schlüter
Heiner Wedemeyer
Markus Cornberg
Christine Falk
Marius Vital
Benjamin Maasoumy
author_facet Laura Buttler
David A. Velázquez-Ramírez
Anja Tiede
Anna M. Conradi
Sabrina Woltemate
Robert Geffers
Birgit Bremer
Vera Spielmann
Julia Kahlhöfer
Anke R.M Kraft
Dirk Schlüter
Heiner Wedemeyer
Markus Cornberg
Christine Falk
Marius Vital
Benjamin Maasoumy
author_sort Laura Buttler
collection DOAJ
description Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1–G3) showing distinct microbial patterns. G1 (n = 39) displayed lowest diversity and highest Enterococcus abundance, G2 (n = 24) was dominated by Bifidobacteria, G3 (n = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n = 33; 86.8%), had highest plasma-levels of Zonulin (p = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections (p = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.
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spelling doaj-art-c0400f4658ef4fb5af3f7b30a9f07c312025-08-20T02:27:07ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2487209Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammationLaura Buttler0David A. Velázquez-Ramírez1Anja Tiede2Anna M. Conradi3Sabrina Woltemate4Robert Geffers5Birgit Bremer6Vera Spielmann7Julia Kahlhöfer8Anke R.M Kraft9Dirk Schlüter10Heiner Wedemeyer11Markus Cornberg12Christine Falk13Marius Vital14Benjamin Maasoumy15Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyGerman Center for Infection Research (DZIF), Hannover-Braunschweig, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyGerman Center for Infection Research (DZIF), Hannover-Braunschweig, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyDecompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1–G3) showing distinct microbial patterns. G1 (n = 39) displayed lowest diversity and highest Enterococcus abundance, G2 (n = 24) was dominated by Bifidobacteria, G3 (n = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n = 33; 86.8%), had highest plasma-levels of Zonulin (p = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections (p = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.https://www.tandfonline.com/doi/10.1080/19490976.2025.2487209Intestinal microbiomefungidysbiosisliver cirrhosismetagenomicsgut barrier
spellingShingle Laura Buttler
David A. Velázquez-Ramírez
Anja Tiede
Anna M. Conradi
Sabrina Woltemate
Robert Geffers
Birgit Bremer
Vera Spielmann
Julia Kahlhöfer
Anke R.M Kraft
Dirk Schlüter
Heiner Wedemeyer
Markus Cornberg
Christine Falk
Marius Vital
Benjamin Maasoumy
Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation
Gut Microbes
Intestinal microbiome
fungi
dysbiosis
liver cirrhosis
metagenomics
gut barrier
title Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation
title_full Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation
title_fullStr Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation
title_full_unstemmed Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation
title_short Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation
title_sort distinct clusters of bacterial and fungal microbiota in end stage liver cirrhosis correlate with antibiotic treatment intestinal barrier impairment and systemic inflammation
topic Intestinal microbiome
fungi
dysbiosis
liver cirrhosis
metagenomics
gut barrier
url https://www.tandfonline.com/doi/10.1080/19490976.2025.2487209
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