Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis - Université de Lille
Article Dans Une Revue Hepatology (Baltimore, Md.) Année : 2020

Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis

Sonja Lang
  • Fonction : Auteur
Yi Duan
  • Fonction : Auteur
Jinyuan Liu
  • Fonction : Auteur
Manolito G. Torralba
  • Fonction : Auteur
Claire Kuelbs
  • Fonction : Auteur
Meritxell Ventura-Cots
  • Fonction : Auteur
Juan G. Abraldes
  • Fonction : Auteur
Francisco Bosques-Padilla
  • Fonction : Auteur
Elizabeth C. Verna
  • Fonction : Auteur
Robert S. Brown
  • Fonction : Auteur
Victor Vargas
  • Fonction : Auteur
Jose Altamirano
  • Fonction : Auteur
Juan Caballeria
  • Fonction : Auteur
Debbie Shawcross
  • Fonction : Auteur
Michael R. Lucey
  • Fonction : Auteur
Guadalupe Garcia-Tsao
  • Fonction : Auteur
Samuel B. Ho
  • Fonction : Auteur
Xin M. Tu
  • Fonction : Auteur
Ramon Bataller
  • Fonction : Auteur
Derrick E. Fouts
  • Fonction : Auteur
Bernd Schnabl
  • Fonction : Auteur

Résumé

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.

Dates et versions

hal-04563863 , version 1 (30-04-2024)

Identifiants

Citer

Sonja Lang, Yi Duan, Jinyuan Liu, Manolito G. Torralba, Claire Kuelbs, et al.. Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis. Hepatology (Baltimore, Md.), 2020, Hepatology (Baltimore, Md.), 71, pp.522-538. ⟨10.1002/hep.30832⟩. ⟨hal-04563863⟩

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