Published online Sep 21, 2022. doi: 10.3748/wjg.v28.i35.5188
Peer-review started: April 12, 2022
First decision: July 13, 2022
Revised: July 26, 2022
Accepted: August 22, 2022
Article in press: August 22, 2022
Published online: September 21, 2022
Chronic hepatitis B virus (HBV) infection (CHB) represents a public health problem that may progress to cirrhosis and hepatocellular carcinoma (HCC). HBV-infected individuals in immune tolerance (IT) are generally not recommended for anti-HBV treatment, owing to the absence of curative treatment and the evidence of a low risk of progressive liver injury in the IT patients. However, recent studies indicated hepatocarcinogenesis may occur in IT-phase patients; the body’s IT status is a key factor affecting the outcome of the disease. Therefore, finding out the factors that affect the prognosis of HBV infection is of paramount significance for the rapid elimination of virus and the reduction of CHB.
The bacterial diversity level and composition varied between CHB, hepatitis B-related liver cirrhosis, and HCC. Gut microbiota of healthy controls is more consistent, whereas those of CHB, hepatitis B-related liver cirrhosis and HCC varied substantially. As the first phase of HBV progression, IT phase provides a favorable immune environment for HBV invasion and long-term existence, then transitions to immune clearance in the third decade. Therefore, in-depth study of the disease status and changes in the body during the IT phase is conducive to the development of new antiviral treatment methods to break the IT of the body and improve the antiviral efficacy and thus improve the long-term prognosis.
This study aimed to find some potential bacteria, linking different pathological mechanisms of IT phase HBV infection and some related metabolites to the IT phase of CHB infection.
Clinical fecal samples from healthy individuals and patients in the IT and IA phases of HBV infection were collected. Next, non-target metabolomics, bioinformatics, and 16S rDNA sequencing analyses were performed.
A total of 293 different metabolites in 14 phyla, 22 classes, 29 orders, 51 families, and 190 genera were identified. The four phyla of Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the most abundant, accounting for 99.72%, 99.79%, and 99.55% in the healthy controls, IT-phase patients, and IA-phase patients, respectively. We further identified 16 genera with different richness in the IT phase and IA phase of HBV infection. Of the 134 named metabolites, 57 were upregulated and 77 were downregulated. A total of 101 different metabolic functions were predicted in this study, with 6 metabolic pathways having the highest enrichments, namely carbohydrate metabolism (14.85%), amino acid metabolism (12.87%), lipid metabolism (11.88%), metabolism of cofactors and vitamins (11.88%), xenobiotic biodegradation (9.9%), and metabolism of terpenoids and polyketides (7.92%).
The composition of the gut microbiota changed in the early stages of HBV infection, and changes in the composition of the gut microbiota can significantly alter gene function, which may have a potential role in HBV-infected patients.
It is relatively difficult to fully understand the causal relationship between gut microbiota and HBV-induced chronic liver disease at different stages in this real-world cross-sectional study. Nevertheless, it should be noted that germ-free animals are good models to study the effect of gut microbiota on human diseases. In a future study, it is imperative to use germ-free animal models and additional biofunctional assays to reveal the cause-effect relationship between gut microbiota and chronic HBV infection.