Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions

Table 1 Gut microbiota alteration and additional findings in hepatitis B virus-related fibrosis

Ref.	Population (n)	Detection method	Gut microbiota alteration	Additional findings
Lu et al[30]	Healthy volunteers (n = 32); HBV carriers (n = 30); CHB (n = 31); Decompensated HBV-LC (n = 31)	qPCR	Phylum	Copies of operons that code for virulence factors markedly increased. Fecal sIgA and TNF-α in decompensated HBV-LC patients were higher than other groups
			Bacteroidetes ↓
			Firmicutes ↓
			Family
			Bifidobacteria/Enterobacteriaceae ↓
Xu et al[142]	Healthy volunteers (n = 15); CHB (n = 16); HBV-LC (n = 16)	qPCR	Species	B. dentium, which was considered to be an opportunistic pathogen, increased in HBV-LC patients. Species composition of Bifidobacterium shifted from beneficial to pathogenic
			(Bifidobacterium specific)
			B. catenulatum ↓
			B. longum ↓
			B. dentinum ↑
Wu et al[143]	Healthy volunteers (n = 38); Decompensated HBV-LC (n = 61); HBV-LT (after LC) (n =74)	qPCR	Species (Lactobacilli specific)	Less complex fecal lactobacilli composition was found especially in decompensated HBV-LC patients
			L. rhamnosus ↓
			L. fermentus ↓
Wei et al[38]	Healthy volunteers (n = 120); HBV-LC (n = 120): CTP-A (n = 40); CTP-B (n = 40); CTP-C (n = 40)	Solexa sequencing	Phylum	A negative correlation was observed between the Child-Turcotte-Pugh scores and Bacteroidetes (P < 0.01)
			Bacteroidetes ↓
			Proteobacteria ↑
			Family
			Enterobacteriaceae ↑
			Genera
			Veillonella ↑
Wang et al[23]	Healthy volunteers (n = 22); CHB (n = 85): CP-A (n = 76); CP-B (n = 9)	16S rRNA sequencing	Family	Streptococcus, Veillonella, Streptococcus and Haemophilus had strong correlations with liver function indices and serum metabolites. They were significantly higher in patients with higher Child-Pugh scores. The gut microbiota may be partially involved in the abnormal accumulation of serum metabolites
			Lachnospiraceae ↓
			Rikenellaceae, ↓
			Porphyromonadaceae ↓
			Ruminococcaceae ↓
			Veillonellaceae ↑
Deng et al[29]	Healthy volunteers (n = 20); HBV-LC (n = 80): CP-A (n = 30); CP-B (n = 31); CP-C (n = 19)	16S rRNA sequencing	Phylum	Gut microbiota alteration mentioned on the left were all independent risk or protective factors for HBV-LC. Serum endotoxin increased in patients with higher CP classes (P = 0.000)
			Firmicutes/Bacteroidetes ↑
			Genera
			Megamonas ↓
			Veillonella ↓
Zeng et al[140]	Healthy volunteers (n = 15); CHB (n = 21); HBV-LC (n = 25); HBV-HCC (n = 21)	16S rRNA sequencing	Phylum	Higher Bacteroidetes/firmicutes ratio represented for higher LPS exposure
			Proteobacteria ↑
			Bacteroidetes ↑
			Firmicutes ↓
			Family
			Bifidobacteria/Enterobacteriaceae ↓
Wang et al[59]	Healthy volunteers (n = 21); CHB (n = 69); F0-1 (n = 25); F2-4 (n = 44)	16S rRNA sequencing	Genera	Genera responsible for bile acid metabolism decreased in CHB fibrosis patients
			Prevotella ↑
			Bacteroides ↓
			Ruminococcus ↓
Chen et al[28]	Healthy volunteers (n = 21); HBV carriers (n = 23); CHB (n = 28); HBV-LC (n = 25)	16S rRNA sequencing	Phylum	HBV-LC patients had higher bacterial network complexity with lower abundance of potential beneficial bacterial taxa
			Actinobacteria ↑
			Bacteroidetes ↓
			Firmicutes ↓
			Proteobacteria ↑
Yang et al[27]	Healthy volunteers (n = 31); HBV carriers (n = 24); CHB (n = 56); HBV-LC (n = 54); HBV-ACLF (n = 52)	16S rRNA sequencing	There are fluctuations in the changes	HBV carriers might be the most suitable donors for FMT for higher α diversity and abundance of potential beneficial bacteria
Wang et al[37]	Healthy volunteers (n = 877); CHB (n = 252); HBV-LC (n = 162); HBV-ACLF (n = 212)	16S rRNA sequencing; metagenomic sequencing	Species	High abundance of Enterococcus is associated with progression while that of Faecalibacterium is associated with regression of HBV-ACLF
			Enterococcus faecium ↑

HBV: Hepatitis B virus; CHB: Chronic hepatitis B; ACLF: Acute-on-chronic liver failure; CP: Child-Pugh scores; CTP, Child-Turcotte-Pugh scores; FMT: Faecal microbiota transplantation; LC: Liver cirrhosis; LT: Liver transplant; qPCR: Quantitative polymerase chain reaction.