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Antagonism Between Gut Ruminococcus gnavus and Akkermansia muciniphila Modulates the Progression of Chronic Hepatitis B.
Chua, Huey-Huey; Chen, Ya-Hui; Wu, Li-Ling; Yang, Hung-Chih; Lin, Chia-Ray; Chen, Huey-Ling; Wu, Jia-Feng; Chang, Mei-Hwei; Chen, Pei-Jer; Ni, Yen-Hsuan.
Afiliación
  • Chua HH; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan.
  • Chen YH; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan.
  • Wu LL; Department and Institute of Physiology, National Yang-Ming Chiao-Tung University College of Medicine, Taipei, Taiwan.
  • Yang HC; Department of Internal Medicine, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • Lin CR; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan.
  • Chen HL; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan; Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan.
  • Wu JF; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan.
  • Chang MH; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan.
  • Chen PJ; Department of Internal Medicine, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Center of Genomic and Precision Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Ho
  • Ni YH; Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan; Center of Genomic and Precision Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan;
Cell Mol Gastroenterol Hepatol ; 17(3): 361-381, 2024.
Article en En | MEDLINE | ID: mdl-38092311
BACKGROUND & AIMS: A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB. METHODS: To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed. RESULTS: Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination. CONCLUSIONS: R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis B Crónica / Clostridiales Límite: Animals / Humans Idioma: En Revista: Cell Mol Gastroenterol Hepatol Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis B Crónica / Clostridiales Límite: Animals / Humans Idioma: En Revista: Cell Mol Gastroenterol Hepatol Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos