Antagonism Between Gut Ruminococcus gnavus and Akkermansia muciniphila Modulates the Progression of Chronic Hepatitis BSummary

Huey-Huey Chua; Ya-Hui Chen; Li-Ling Wu; Hung-Chih Yang; Chia-Ray Lin; Huey-Ling Chen; Jia-Feng Wu; Mei-Hwei Chang; Pei-Jer Chen; Yen-Hsuan Ni

Cellular and Molecular Gastroenterology and Hepatology (Jan 2024)

Antagonism Between Gut Ruminococcus gnavus and Akkermansia muciniphila Modulates the Progression of Chronic Hepatitis BSummary

Huey-Huey Chua,
Ya-Hui Chen,
Li-Ling Wu,
Hung-Chih Yang,
Chia-Ray Lin,
Huey-Ling Chen,
Jia-Feng Wu,
Mei-Hwei Chang,
Pei-Jer Chen,
Yen-Hsuan Ni

Affiliations

Huey-Huey Chua: Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
Ya-Hui Chen: Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
Li-Ling Wu: Department and Institute of Physiology, National Yang-Ming Chiao-Tung University College of Medicine, Taipei, Taiwan
Hung-Chih Yang: 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
Chia-Ray Lin: Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
Huey-Ling Chen: 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
Jia-Feng Wu: Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
Mei-Hwei Chang: Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
Pei-Jer Chen: 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 Hospital, Taipei, Taiwan
Yen-Hsuan Ni: 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; Medical Microbiota Center, National Taiwan University College of Medicine, Taipei, Taiwan; Correspondence Address correspondence to: Yen-Hsuan Ni, MD, PhD, Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, 15F, No. 8, Chung-Shan S. Road, Taipei 100226, Taiwan.

Journal volume & issue: Vol. 17, no. 3
pp. 361 – 381

Abstract

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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.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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