Background Increasing evidence suggests that the gut microbiota has evolved as a new important player in the pathogenesis of hepatitis B virus-induced chronic liver disease, including chronic hepatitis, cirrhosis. However, the composition and structure alteration of the gut microbiota associated with the stage and progression of HBV infection remains unknown. Hence, the aim of the study is to elucidate the microbial influence which contributes to the microbial shift of HBV patients in different stages.

Methods All subjects enrolled had clinic test performed in the Zhongshan Hospital, Xiamen University. A total of 62 subjects were finally selected for inclusion in this study, including 7 healthy individuals, 13 HBeAg negative chronic HBV infection patients (HNCHI), 6 HBeAg negative chronic hepatitis B patients (HNCHB), 5 HBeAg positive chronic hepatitis B patients (HPCHB) and 31 decompensated cirrhosis after hepatitis B patients (DCAHB) matched in age, gender and body mass index (BMI). Stools from all subjects were collected to extract DNA, then for 16S rDNA high-throughput sequencing and further compared by the bacterial diversity, community and structure, differential taxa analysis.

Results DCAHB patients showed decreased gut bacterial diversity and more unique OTU numbers compared to the other four groups, suggesting that DCAHB is distinctive, which could further be confirmed by the PCA analysis. In phyla level, the relative abundance of Fusobacteria and Proteobacteria increased while Firmicutes content decreased from the health, HNCHI, HNCHB, HPCHB to DCAHB group. In genus level, the high level of Streptococcus, Veillonella, Enterobacteriaceae, Lactobacillus and Haemophilus, while decreased Clostridiaceae, Phascolarctobacterium, Coprococcus and Ruminococcaceae in DCAHB conform the disease progression state. In addition, LEfSe analysis reveals that Bacteroides fragilis, Bacteroides eggerthii, Veillonella dispar, Streptococcus anginosus, Corprococcus eutactus and Akkermansia muciniphila could serve as target microorganism for the further investigation.

Conclusions These compositional and structural changes in the gut microbiota in varied stage HBV patients suggest the potential contributions of gut microbiota to the progression of HBV infection and thus provide new insight into gut microbiota-targeted interventions to improve the prognosis of this disease.