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, according to investigators.
While Ruminococcus gnavus promotes immune tolerance and therefore HBV persistence, Akkermansia muciniphila stimulates the immune system, promoting viral clearance, reported lead author Huey-Huey Chua, MD, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.
These findings could lead to new therapeutic strategies, such as administration of the secretory products of A. muciniphila, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.
“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”
They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection.
R. gnavus was the most abundant species among IT patients, whereas A. muciniphila was most abundant among patients in the IA phase. Higher levels of A. muciniphila were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.
Further experiments with mouse models revealed that R. gnavus modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, A. muciniphila removes cholesterol and secretes metabolites that inhibit growth and function of R. gnavus.
“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.
They went on to describe several therapeutic strategies worth further investigation.
“A key step to promote switching from the IT to IA phase is to lessen the richness of R. gnavus and bile acid bioconversion from cholesterol,” they wrote. The secretory products of A. muciniphila that successfully ameliorate the burden of R. gnavus outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of A. muciniphila while inhibiting the detrimental effects of R. gnavus may have translational value for CHB.”
The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.
Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.
This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential A. muciniphila–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of A. muciniphila supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.
Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.
Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.
This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential A. muciniphila–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of A. muciniphila supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.
Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.
Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.
This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential A. muciniphila–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of A. muciniphila supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.
Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.
, according to investigators.
While Ruminococcus gnavus promotes immune tolerance and therefore HBV persistence, Akkermansia muciniphila stimulates the immune system, promoting viral clearance, reported lead author Huey-Huey Chua, MD, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.
These findings could lead to new therapeutic strategies, such as administration of the secretory products of A. muciniphila, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.
“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”
They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection.
R. gnavus was the most abundant species among IT patients, whereas A. muciniphila was most abundant among patients in the IA phase. Higher levels of A. muciniphila were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.
Further experiments with mouse models revealed that R. gnavus modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, A. muciniphila removes cholesterol and secretes metabolites that inhibit growth and function of R. gnavus.
“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.
They went on to describe several therapeutic strategies worth further investigation.
“A key step to promote switching from the IT to IA phase is to lessen the richness of R. gnavus and bile acid bioconversion from cholesterol,” they wrote. The secretory products of A. muciniphila that successfully ameliorate the burden of R. gnavus outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of A. muciniphila while inhibiting the detrimental effects of R. gnavus may have translational value for CHB.”
The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.
, according to investigators.
While Ruminococcus gnavus promotes immune tolerance and therefore HBV persistence, Akkermansia muciniphila stimulates the immune system, promoting viral clearance, reported lead author Huey-Huey Chua, MD, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.
These findings could lead to new therapeutic strategies, such as administration of the secretory products of A. muciniphila, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.
“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”
They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection.
R. gnavus was the most abundant species among IT patients, whereas A. muciniphila was most abundant among patients in the IA phase. Higher levels of A. muciniphila were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.
Further experiments with mouse models revealed that R. gnavus modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, A. muciniphila removes cholesterol and secretes metabolites that inhibit growth and function of R. gnavus.
“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.
They went on to describe several therapeutic strategies worth further investigation.
“A key step to promote switching from the IT to IA phase is to lessen the richness of R. gnavus and bile acid bioconversion from cholesterol,” they wrote. The secretory products of A. muciniphila that successfully ameliorate the burden of R. gnavus outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of A. muciniphila while inhibiting the detrimental effects of R. gnavus may have translational value for CHB.”
The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY