The role of gut microbiota in hepatitis B disease progression and treatment.

Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the 'Gut-Liver Axis', where exchanges happen bi-directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony-free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and faecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.

Chen B ，Huang H ，Pan CQ 《-》

Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy.

Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The liver is connected to the small intestine by the bile duct, which carries bile formed in the liver to the intestine. Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Human intestines contain a wide diversity of microbes, collectively termed the 'gut microbiota'. Gut microbiota play a significant role in host metabolic processes and host immune modulation, and influence host development and physiology (organ development). Altered gut microbiota is a common complication in liver disease. Changes in intestinal microbiota seem to play an important role in induction and promotion of HBV-induced chronic liver disease progression, and specific species among the intestinal commensal bacteria may play either a pathogenic or a protective role in the development of HBV-induced chronic liver disease. Thus, the gut microbiome may represent fertile targets for prevention or management of HBV-induced chronic liver disease. Faecal microbiota transplantation (FMT) may be a useful therapy for HBV-related disease in the future. However, the data available in this field remain limited, and relevant scientific work has only just commenced. New technologies have enabled systematic studies of gut microbiota, and provided more realistic information about its composition and pathological variance. This review summarizes the cutting edge of research into the relationship between gut microbiota and HBV-induced chronic liver disease, and the future prospects of FMT therapy.

Kang Y ，Cai Y 《-》

Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.

The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited. In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals. Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals. The 16S rDNA gene amplification products were sequenced. Bioinformatic analysis including alpha diversity and PICRUSt was performed. A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected. The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially. The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls. Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals. Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes. Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.

Zeng Y ，Chen S ，Fu Y ，Wu W ，Chen T ，Chen J ，Yang B ，Ou Q ... -  《-》

Gut microbiota dysbiosis in patients with hepatitis B virus-related cirrhosis.

Chronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to liver cirrhosis. The relationship between hepatitis B virus-related cirrhosis (HBV-RC) and gut microbiota dysbiosis is still unclear. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in the patients with liver cirrhosis and healthy individuals. We analyzed the gut microbiome in patients with HBV-RC and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. A total of 113 genera, 85 families, 57 orders, 44 classes and 21 phyla were performed. Our results suggests that the composition of the gut microbiota had changed in the early stages of cirrhosis. We further identified more than 17 genera with different richness in compensated and decompensated cirrhosis groups. PICRUSt analysis showed that changes in bacterial composition can lead to significant changes in gene function, which may be one of the causes of liver cirrhosis. Our study demonstrated that the composition of gut microbiota changed at different phases of HBV-RC. Gut microbiome transformation may be a biological factor in the progression of cirrhosis.

Shu W ，Shanjian C ，Jinpiao L ，Qishui O ... -  《Annals of Hepatology》

Entecavir therapy reverses gut microbiota dysbiosis induced by hepatitis B virus infection in a mouse model.

Chronic hepatitis B virus (HBV) infection is a global public health problem. The gut microbiota has been linked to pathogenesis of liver diseases induced by chronic HBV infection. This study established a recombinant adeno-associated virus serotype 8 (rAAV8)-mediated persistent HBV infection mouse model. Entecavir (ETV) treatment significantly decreased the HBV DNA load both in serum and the liver. The comparison of gut microbiota composition of rAAV8-HBV-infected mice and ETV-treated mice with healthy controls was carried out using 16S rDNA sequencing analysis of caecal content samples. The intestinal microbiota alpha diversity of rAAV8-HBV-infected mice decreased, and significantly restored after 4 weeks of ETV therapy. Blautia and Clostridium sensu stricto significantly decreased in rAAV8-HBV-infected mice and was negatively correlated with both HBsAg and HBeAg levels. On the contrary, the Butyricicoccus and Prevotellaceae NK3B31 groups exhibited positive correlation with HBsAg and HBeAg. Furthermore, it was observed that Akkermansia, a known gut barrier-protecting bacterium, significantly decreased in rAAV8-HBV-infected mice and was restored to the level of that in healthy controls after ETV therapy, while the abundance of Akkermansia was negatively correlated with HBV DNA load both in serum and the liver. Taken together, the results showed that dysbiosis of gut microbiota developed in the persistent HBV-infected mice and was effectively reversed by ETV treatment, shedding light on the mechanisms of gut microbiota on HBV-persistent infection and antiviral therapy.

Li X ，Wu S ，Du Y ，Yang L ，Li Y ，Hong B ... -  《-》