Interplay between viral infections and gut microbiota dysbiosis: Mechanisms and therapeutic potential

Table 3 Gut microbiota composition in hepatitis B virus/hepatitis C virus cirrhotic patients

Ref.	Total cases (n)	Cirrhosis-related cases (n)	Methodology	Increased taxa	Decreased taxa	Limitations	Conclusion
Elsherbiny et al[62], 2025	80 (60 CHC patients + 20 HCs)	Non-cirrhotic CHC (n = 60)	16S rRNA sequencing (V3-V4)	SVR group: Elusimicrobium, Christensenellaceae R-7 group, Catenibacterium, Oceanobacillus, Candidatus Melainabacteria. Relapsed group: Prevotella, Bifidobacterium, Lactobacillus, Megasphaera, Mitsuokella. Non-treated group: Faecalibacterium, Asteroeplasma, Eubacterium coprostanoligenes, Lachnospiraceae, Akkermansia, Muribaculaceae	SVR group: Actinobacteria. All CHC vs HCs: Reduced diversity; Bacteroides, Agathobacter, Parabacteroides	Single-center design; modest sample size; unmeasured confounders (diet, lifestyle)	DAA therapy markedly modulates gut microbiota; SVR restores microbial diversity and composition toward that of HCs, whereas relapse is characterized by persistent dysbiosis
Huang et al[63], 2023	120 subjects (180 samples)	Control: 60 HCs. CHC (pre-DAA): 60 patients. SVR24 (post-DAA): 60 patients	16S rRNA sequencing (V3-V4)	Ruminococcaceae, Eubacterium, Agathobacter, Alistipes, Bifidobacterium, Klebsiella, Lactobacillus, Actinobacteria, Firmicutes, Lactobacillus	Bacteroidetes, Lachnoclostridium	Relatively small sample size; short follow-up (24 weeks); unmeasured confounders (diet, smoking); baseline differences in liver function between CHC and control groups	Gut microbiota diversity and composition remained unchanged 6 months after DAA therapy; minor differences in CHC vs controls were unaffected by SVR
Honda et al[64], 2025	70 CHB patients + 8 HCs	Functional cure: 18 (HBsAg-, HBV DNA-). Low-titer DNA: 40. High-titer DNA: 12. HC: 8	16S rRNA sequencing (V3-V4)	Clostridium bartlettii, Butyricimonas, Coprococcus catus, Bifidobacterium breve, Campylobacter	Not reported	Small sample size; exploratory design; in vitro SCFA concentrations may not reflect physiological levels in the liver	Butyrate-producing bacteria are enriched in HBsAg-negative patients; sodium butyrate directly suppresses HBsAg production in infected hepatocytes, especially post-infection
Inoue et al[65], 2025	272 (174 active HCV, 75 post-SVR, 23 HCs)	CH-HCV: 95, LC/HCC-HCV: 79, CH-SVR: 29, LC/HCC-SVR: 46, healthy: 23	16S rRNA sequencing; fecal BA profiling; RNA-seq	Blautia, Fusicatenibacter, Roseburia, Faecalibacterium, Subdoligranulum, Collinsella	Streptococcus, Streptococcus salivarius, Eubacterium hallii group, Ruminococcus torques group	Cohort separation for multi-omic analyses; limited SVR48 sample size; partially uses database-derived RNA-seq data	HCV eradication partially restores gut dysbiosis and BA profiles, with post-SVR Blautia enrichment correlating with improved liver fibrosis and function
Li et al[66], 2025	88	AHE-elderly: 58, HCs-elderly: 30, self-healing: 46, non-self-healing: 12	16S rRNA sequencing	AHE-elderly vs HC: Firmicutes, Lactobacillales, Bacilli, Streptococcaceae. Non-self-healing vs self-healing: Bifidobacteriaceae, Bacteroidia, Bacteroides fragilis	AHE-elderly vs HC: Proteobacteria, Bacteroidetes. Self-healing vs non-self-healing: Firmicutes, Bacillus, Lactobacillus, Streptococcus	No significant difference in alpha diversity; lack of longitudinal data; unclear causal relationship between microbiota changes and HEV infection	Bacteroidetes distinguish AHE patients from controls, with Bacteroides fragilis enriched in non-self-healing cases and serving as a predictive biomarker
Li et al[67], 2025	79	HBC: 46, HCs: 33, BA-N: 24, BA-H: 22	16S rRNA sequencing (V4-V5)	Streptococcus, Veillonella, Lactobacillales	Bacteroides, Akkermansia, Clostridiales	Cross-sectional design; small sample size; no BA composition or metabolomic analysis; potential confounders (diet, medication) not fully addressed	HBC dysbiosis features reduced beneficial taxa and increased opportunistic pathogens; Akkermansiaceae decline and Lactobacillales rise with elevated BAs, which correlate with higher Child-Pugh scores, suggesting gut microbiota–BA crosstalk drives HBC progression
Shi et al[68], 2025	123	HBV-LC: 83, HC: 40, MELD < 21: 68, MELD ≥ 21: 15, CTP-C: 22	16S rRNA sequencing (V3-V4)	Klebsiella, Streptococcus, Fusobacterium, Enterococcus	Alistipes, Lachnospira, Agathobacter, Parabacteroides, Roseburia	Single-center design; modest sample size; cross-sectional design limits causal inference; 16S rRNA does not capture full functional potential	HBV-LC patients show gut dysbiosis marked by enrichment of pathobionts (Klebsiella, Streptococcus) and loss of SCFA-producers (Alistipes, Lachnospira), with metabolite alterations (tocopherols, 21-hydroxypregnenolone) linked to specific microbial shifts and disease severity
Honda et al[69], 2021	42	Pre-DAA: 14, EOT: 14, post-24: 14 (samples from the same 14 patients)	16S rRNA sequencing (V3-V4)	Faecalibacterium, Bacillus	Bacteroides, Fusobacterium	Small sample size; lack of a HC group; intra-personal comparison only; cannot determine if pre-treatment microbiota differed from healthy individuals	HCV eradication did not significantly alter overall gut microbiota diversity but increased beneficial taxa such as Faecalibacterium and Bacillus at 24 weeks post-treatment, indicating a positive compositional shift despite stable global diversity
Liu et al[70], 2024	62	OBI: 24, HBV carriers: 18, HCs: 20	16S rRNA sequencing (V3-V4)	Subdoligranulum, Megamonas	Faecalibacterium	Small sample size; all participants were male; potential unmeasured confounders (diet); cannot establish causality	OBI is characterized by enrichment of Subdoligranulum, potentially driving IFN-γ/IL-17A–mediated immune activation that suppresses HBV replication, alongside depletion of beneficial Faecalibacterium
Yan et al[71], 2023	90	30 HCs + 30 HBV-LC + 30 HBV-HCC	16S rRNA sequencing (V3-V4) + flow cytometry	Proteobacteria, Actinobacteriota, Campylobacterota, Streptococcaceae, Enterobacteriaceae, Klebsiella, Streptococcus	Bacteroidota, Firmicutes, Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Rikenellaceae, Barnesiella, Agathobacter, Prevotella	Cross-sectional design; small sample size; dietary/age confounders; 16S limits function	HBV-CLD progression involves enrichment of pro-inflammatory taxa and depletion of butyrate producers, correlating with T-cell immunosuppression
Hsu et al[72], 2022	126	HCV patients: 42 (pre-Tx: 42, post-Tx: 42), HCs: 84	Prospective cohort; 16S rRNA (V3-V4), DADA2, LEfSe; matched controls	Coriobacteriaceae, Staphylococcaceae, Peptostreptococcaceae, Succinivibrionaceae	Morganellaceae, Pasteurellaceae, Moraxellaceae	Short-term follow-up (12 weeks post-DAA); modest sample size; exploratory differential taxa need validation; cirrhosis subgroup is small	Gut microbiota differs between HCV patients and HCs, but DAA-induced viral eradication does not significantly alter diversity or composition, suggesting viremia is not the main driver of dysbiosis
Wang et al[73], 2025	20	Group M (minimal injury): 9, group S (significant injury): 11	Human: Metagenomic sequencing. Mouse: 16S rRNA sequencing (V3-V4), FMT	Parabacteroides distasonis, Bacteroides dorei, Bacteroides finegoldii, Bacteroides ovatus, Bacteroides clarus	Eubacterium sp. CAG_180, Gemmiger formicilis, Oscillibacter sp. ER4, Subdoligranulum variabile, Faecalibacterium sp. CAG_74_58_120	Small sample size (n = 20); FMT from a single cirrhotic donor; mechanistic pathways (BA crosstalk) require further validation	Gut dysbiosis contributes to histological liver damage in early CHB. FMT from an HBV-cirrhosis donor aggravated fibrosis in mice, implicating BA-microbiota crosstalk in disease progression
Yang et al[74], 2023	950	Viral hepatitis: 656 (HBV: 546, HCV: 86, HEV: 24), HC: 294	Meta-analysis of 13 studies; 16S rRNA sequencing (multiple regions)	Butyricimonas, Escherichia-Shigella, Lactobacillus, Veillonella	Clostridia_UCG-014, Dorea, Monoglobus, Ruminococcus	Lack of HAV/HDV data; variability in sequencing regions/platforms; cannot establish causality	Viral hepatitis reduces gut microbial diversity, with specific taxa and functions (tryptophan metabolism, LPS biosynthesis) serving as potential biomarkers and contributing to disease pathogenesis

CHC: Chronic hepatitis C; HC: Healthy control; SVR: Sustained virologic response; DAA: Direct acting antiviral; CHB: Chronic hepatitis B; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; SCFA: Short-chain fatty acid; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; CH: Chronic hepatitis; LC: Liver cirrhosis; BA: Bile acid; AHE: Acute hepatitis E; HBC: Hepatitis B-related cirrhosis; MELD: Model for end-stage liver disease; CTP: Child-Turcotte-Pugh; EOT: End of treatment; OBI: Occult hepatitis B virus infection; IFN: Interferon; IL: Interleukin; CLD: Chronic liver disease; FMT: Fecal microbiota transplantation; HEV: Hepatitis E virus; HAV: Hepatitis A virus; HDV: Hepatitis D virus; LPS: Lipopolysaccharide.