Evidence map›Paper›PMID 41996830›Full record

ArticleJHEP reports : innovation in hepatology2026

Peptide YY reduces cytotoxicity of Candida albicans in alcohol-associated liver disease.

Henriette Kreimeyer, Marcos F Fondevila, Aenne Harberts, Fernanda Raya Tonetti, David Schöler, Eliane Münte, Phillipp Hartmann, Cristina Llorente, Bernhard Hube, Salomé LeibundGut-Landmann and 3 more

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In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Henriette KreimeyerDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Marcos F FondevilaDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Aenne HarbertsDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Fernanda Raya TonettiDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
David SchölerDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Eliane MünteDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Phillipp HartmannDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Cristina LlorenteDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Bernhard HubeDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany; Institute of Microbiology, Friedrich Schiller University, Jena, Germany.
Salomé LeibundGut-LandmannSection of Immunology, Vetsuisse Faculty and Institute of Experimental Immunology, University of Zürich, 8057 Zurich, Switzerland; Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.
Peter StärkelDepartment of Hepatology and Gastroenterology, Cliniques Universitaires Saint Luc, Brussels, Belgium.
AlcHepNet Investigators
Bernd SchnablDepartment of Medicine, University of California San Diego, La Jolla, California, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA. Electronic address: beschnabl@health.ucsd.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsTransitioning from yeast to hyphal morphology enables Candida albicans (C. albicans) to secrete candidalysin, invade the intestinal mucosa and translocate to the blood stream. Patients with alcohol-associated hepatitis show increased intestinal abundance of C. albicans, and the candidalysin-encoding gene is associated with reduced survival. Paneth cell-derived peptide YY (PC-PYY) inhibits hyphal growth of C. albicans. In this study, we evaluated the potential of different C. albicans strains isolated from patients with alcohol-associated hepatitis to cause systemic infections and explored the therapeutic potential of PC-PYY in ethanol-induced liver disease in mice.

methodsC. albicans strains isolated from fecal samples of patients with alcohol-associated hepatitis (n = 105) were co-cultured with intestinal epithelial Caco-2 cells to assess in vitro cytotoxicity. Caco-2 cells and primary mouse hepatocytes were incubated with C. albicans in the presence or absence of PC-PYY. Mice were subjected to a chronic plus binge ethanol-feeding model.

resultsC. albicans strains isolated from stool of patients with alcohol-associated hepatitis induced significant cytotoxicity in Caco-2 cells, and high cytotoxicity was associated with worse 30-day survival (log-rank p = 0.032). This cytotoxicity was primarily mediated by the hyphal form and largely driven by candidalysin. PC-PYY significantly reduced C. albicans-induced cytotoxicity in Caco-2 cells (Wilcoxon rank-sum test, p = 0.015) and in primary mouse hepatocytes (p = 0.03) compared with a scrambled peptide control, by inhibiting hyphal morphogenesis. The peptide YY-to-chromogranin A ratio in intestinal crypts was significantly increased in ethanol-fed mice compared with both isocaloric (p = 0.005) and antifungal-treated controls (p = 0.009), indicating that fungal overgrowth stimulates PC-PYY release. In ethanol-fed mice, PC-PYY administration attenuated liver injury (p = 0.032) and steatosis (p = 0.0498) and reduced fecal hyphae formation (p = 0.0159).

conclusionPYY inhibits filamentous growth of C. albicans in vitro and alleviates ethanol-induced liver disease in mice, highlighting its potential as a therapy for patients with alcohol-associated liver disease. IMPACT AND IMPLICATIONS: Candida albicans (C. albicans) and particularly its toxin candidalysin are associated with poor outcomes in patients with alcohol-associated hepatitis but the extent to which the cytotoxicity of individual C. albicans strains influences patient survival, and the role of Paneth cell-derived PYY (PC-PYY) in this context remains elusive. This study identifies a link between the cytotoxic effect of patient-derived C. albicans strains and survival in patients with alcohol-associated hepatitis and demonstrates that PC-PYY plays a protective role in ethanol-induced liver disease by limiting candidalysin-producing hyphae. Our work provides insight into why some patients with alcohol-associated liver disease have worse outcomes and highlights the potential of PC-PYY as a therapy for patients with alcohol-associated liver disease.

Indexed as

alcoholic liver diseaseantimicrobial peptideGut liver axismicrobiomemicrobiotamycobiome

Identifiers

PMID41996830
PMCPMC13101792

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.