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

Table 1 Human viruses interact with bacteria either directly (via bacterial products that facilitate infection) or indirectly (through host environment changes that favor bacterial colonization)

Viruses	Bacterial partner(s)	Mechanistic basis	Ref.
Direct interactions
Murine norovirus	E. cloacae, enteric microbiota	Bacterial histo-blood group antigen analogs support persistent viral infection in the gut	[8,9]
Influenza virus	Staphylococcus aureus	Bacterial proteases activate viral hemagglutinin through cleavage	[10]
Rotavirus	Gut microbiota (e.g., Escherichia coli, Bacteroides thetaiotaomicron)	Bacterial factors promote viral infectivity while reducing antibody neutralization	[11]
Reovirus T3SA+	Enteric bacteria (Escherichia coli, etc.)	Bacterial lipopolysaccharide mediates enhanced viral binding and replication efficiency	[12]
HIV	Mycobacterium tuberculosis	Mycobacterial components enhance HIV transcriptional activity	[13]
Indirect interactions
Adenovirus	S. pneumoniae	Enhances bacterial attachment to respiratory epithelial cells	[14]
Rhinovirus	Respiratory pathogens	Increases the expression of host cell adhesion molecules for bacterial binding	[15]
Measles virus	Multiple opportunistic pathogens	Systemic immune suppression facilitates secondary bacterial infections	[16,17]
Herpesviruses	Porphyromonas gingivalis, Bacteroides forsythus (now Tannerella forsythia), Campylobacter rectus	Viral immunosuppression enables bacterial colonization of the oral mucosa	[18]
Parainfluenza virus	Streptococcus pneumoniae, Haemophilus influenzae	Viral infection increases bacterial adhesion to the respiratory epithelium	[19,20]

HIV: Human immunodeficiency virus.

Table 2 Dysbiosis of gut microbiota in individuals with human immunodeficiency virus infection

Ref.	Total cases (n)	HIV-related cases (n)	Methodology	Increased taxa	Decreased taxa	Limitations	Conclusion
Rhoades et al[44]	105 (≥ 55 years)	58 LTC-HIV+	16S rRNA sequencing (V4)	Fusobacterium, Lactobacillus, Bifidobacteriales, Prevotella (in low CD4+)	Clostridia (SCFA producers), Oxalobacter, Streptococcus (vs HIV-)	Cross-sectional design; cannot establish causality; majority Caucasian male cohort limits generalizability	LTC-HIV+ individuals show gut dysbiosis - oral taxa enriched, butyrate producers depleted - with Prevotella inversely correlating with CD4+ counts, linking microbial shifts to immune dysfunction and chronic inflammation
Lu et al[45]	91	61 HIV	Metagenomics sequencing	Faecalibacterium prausnitzii, Subdoligranulum sp., Coprococcus comes, Prevotella copri, Prevotella stercorea, Bacteroides coprophilus, Bacteroides coprocola, Bacteroides intestinalis, Bacteroides salyersiae	Bacteroides	Small sample size; cross-sectional; single population (Chinese); ART regimen effects not fully differentiated	HIV infection causes gut dysbiosis; increased butyrate producers (F. prausnitzii, Subdoligranulum sp., C. comes) link to poor CD4+ T-cell recovery and activation; microbiota modulation may aid immune reconstitution
Cook et al[46]	383	HIV- (200) HIV+ undetectable (< 20 c/mL, n = 66) HIV+ suppressed (20-200 c/mL, n = 72) HIV+ viremic (> 200 c/mL, n = 45)	16S rRNA sequencing (V4); IPTW-adjusted models	Viremic group: Peptoniphilus, Porphyromonas, Prevotella, Murdochiella	Viremic group: Bacteroides, Brachyspira, Faecalibacterium, Helicobacter. All HIV+ groups: Bacteroides	Lack of dietary data; residual confounding possible; 16S limits species-level resolution; no data on time since ART initiation	HIV viremia correlates with rectal dysbiosis in a dose-dependent manner; viremic individuals show a pro-inflammatory microbiota (Prevotella, Porphyromonas), while suppressed/undetectable viremia associates with milder dysbiosis
Villar-García et al[47]	44 (HIV+, on HAART)	22 immunologic responders, 22 immunologic non-responders	16S rDNA gene sequencing	Megamonas, Desulfovibrionales (Proteobacteria)	Clostridiales (esp. Clostridiaceae, Catenibacterium), Lachnospiraceae, Proteobacteria	Small sample size; did not analyze fungal mycobiome (including probiotic colonization); cannot establish causality; short intervention period	Saccharomyces boulardii reduced pro-inflammatory Clostridiaceae; immunologic non-responders had higher baseline Lachnospiraceae and Proteobacteria
Dillon et al[48]	32	18 untreated HIV+	16S rRNA sequencing (colonic mucosa and stool)	Prevotella stercorea	Butyrate-producing bacteria: Roseburia intestinalis, Faecalibacterium prausnitzii, Eubacterium rectale (in colonic mucosa)	Small cross-sectional study; sexual preference unmatched; fecal butyrate not measured	HIV reduces colonic butyrate-producing bacteria (e.g., Roseburia intestinalis); low abundance links to microbial translocation and immune activation; butyrate may protect against T cell activation and HIV replication
Dinh et al[49]	21 HIV+ on ART, 16 HIV- controls	21 (chronic HIV, suppressed VL)	16S rRNA pyrosequencing (V3-V5 region)	Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, Barnesiella	Rikenellaceae, Alistipes	Small sample size; exploratory design; no correction for multiple comparisons; immune activation markers not assessed	ART-treated, virologically suppressed HIV+ individuals show gut dysbiosis with increased Enterobacteriaceae and decreased Alistipes, correlating with elevated sCD14 and inflammatory cytokines (IL-1β, TNF-α)
Lee et al[50]	HIV+ on ART: 26 (16 oIR, 10 sIR) HIV- controls: 20	26 (all on suppressive ART)	16S rRNA sequencing (V4 region, rectal swabs)	Fusobacterium (phylum: Fusobacteria), Gallicola, Bilophila	Lactobacillales, Corynebacterium	Small sample size; all male participants; dietary data not collected; rectal swabs may not fully reflect luminal microbiota	Poor CD4+ recovery on ART associates with increased Fusobacterium, elevated T-cell activation/Tregs, and reduced naïve CD4+ cells
Machiavelli et al[51]	38 (19 mother-child pairs)	12 HEU children; 12 HIV+ mothers	16S rRNA sequencing (V3-V4 region)	HEU children: Faecalibacterium prausnitzii, Prevotella copri, Lachnospiraceae, Klebsiella, Lactococcus, Ruminococcaceae, Enterobacteriaceae	HEU children: Bacteroides uniformis, Paraprevotella	Cross-sectional, small sample; breastfeeding differences between HEU and unexposed children; functional predictions inferred, not measured	HEU children of HIV+ mothers show altered gut taxa and predicted metagenome without changes in diversity, growth, or inflammation markers
Ling et al[52]	83 (Chinese population)	67 HIV+ (35 HAART-naïve, 32 HAART-treated)	16S rRNA pyrosequencing (V1-V3 regions)	Firmicutes, Prevotella, Faecalibacterium, Phascolarctobacterium, Butyricicoccus, Erysipelotrichaceae incertae sedis, Catenibacterium, Dorea, Enterobacter, Enterococcus, Megamonas	Bacteroidetes, Bacteroides, Dialister, Clostridium XIVa, Clostridium XIVb, Barnesiella, Coprococcus	Cross-sectional; all male; sexual behavior not controlled; fecal samples may not reflect mucosa-associated microbiota	HIV-1 infection causes gut dysbiosis (↑ Firmicutes/Bacteroidetes, pro-inflammatory genera); key taxa correlate with inflammation; short-term HAART only partially restores the microbiota
Liu et al[53]	36 (35 male, 1 female)	14 HIV+ (all ART-treated)	16S rRNA sequencing (V3-V4 region)	Fusobacteria, Proteobacteria, Leptotrichiaceae, Desulfovibrionaceae, Enterobacter, Paraprevotella, Allisonella, Anaerovibrio, Howardella	Firmicutes, Lachnospiraceae, Oxalobacteraceae, Eggerthella, Barnesiella, Odoribacter, Oscillospira, Oxalobacter, Roseburia, Alistipes	Small, mostly male cohort; observational; prebiotic/probiotic use uncontrolled; genus-level data limits species resolution	HIV and aging interact to alter the stool microbiome; age-related taxa changes and associations with SCFAs, diet, and inflammation differ by HIV status
Yang et al[54]	16	8 HIV+ (HAART-naïve, low CD4 counts in 6/8)	16S rRNA sequencing (V3-V4)	Proteobacteria, Burkholderia (specifically Burkholderia fungorum), Bradyrhizobium (specifically Bradyrhizobium pachyrhizi), Ralstonia, Fusobacterium	Firmicutes, Lactobacillus	Small sample; case-control design limits causation; no HAART-treated comparison; clinical symptom correlations limited	HIV-induced immunosuppression reduces gut colonization resistance, enabling environmental bacteria (B. fungorum, B. pachyrhizi) invasion and loss of beneficial commensals, causing dysbiosis linked to immune dysfunction

HIV: Human immunodeficiency virus; LTC: Long-term care; SCFA: Short-chain fatty acid; IPTW: Inverse-probability-of-treatment weighting; ART: Antiretroviral therapy; Tregs: Regulatory T cell; HAART: Highly active antiretroviral therapy; IL: Interleukin; TNF: Tumor necrosis factor; oIR: Optimal immune reconstitution; sIR: Suboptimal immune reconstitution; HEU: Human immunodeficiency virus-exposed uninfected children.

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.

Table 4 Studies investigating microbiota and coronavirus disease 2019

Ref.	COVID-related cases (n)	Methodology	Increased taxa	Decreased taxa	Limitations	Conclusion
de Nies et al[119], 2023	118 subjects COVID-19: 61 (asymptomatic-moderate). Control: 57	Metagenomics, metatranscriptomics, MAG reconstruction, VF/ARG prediction, virome analysis	Prevotella stercorea, Prevotella spp. CAG 520, Roseburia spp. CAG 471, Firmicutes (AM10); Betaherpesvirus; Rotavirus C; VFs & AMR genes (Acidaminococcaceae, Erysipelatoclostridiaceae)	Turicibacter sanguinis, Roseburia faecis, Firmicutes (CAG 145)	Limited to asymptomatic-moderate cases; single-region cohort (Luxembourg); unclear mechanisms linking SARS-CoV-2 to VF/ARG expression	COVID-19 increases the virulence and AMR potential of commensals despite minimal taxonomic shifts, suggesting enhanced pathogenic potential of the gut microbiota
Li et al[120], 2025	121 participants total, NC: 53 (no COVID-19), C3M: 27 (3 months post-recovery), C6M: 41 (6 months post-recovery)	Metagenomic shotgun sequencing; ITS sequencing for fungi	Blautia massiliensis, Kluyveromyces spp., Bacteroides xylanisolvens, Phocaeicola vulgatus, Weissella confusa, Streptococcus thermophilus, Asterotremella spp., Gibberella spp.	Blautia wexlerae, Bifidobacterium pseudocatenulatum, Bifidobacterium longum, Eubacterium rectale, Anaerobutyricum hallii, Pyrenochaeta spp.	Cross-sectional design; excluded long COVID; smaller 3-month group; not generalizable to severe or unvaccinated cases	Mild COVID-19 induces long-term gut bacterial and fungal alterations lasting ≥ 6 months, with partial recovery and persistence of some pathogens
Zhang et al[121], 2023	187 recovered patients (84 symptomatic)	16S rRNA sequencing; clinical surveys (SF-36, SAS, SDS); lab tests; pulmonary function; chest CT	Veillonella	SCFA-producers: Eubacterium hallii group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, Eubacterium ventriosum group, Agathobacter	Single-center, cross-sectional; no longitudinal monitoring; diet/Lifestyle not fully controlled; mechanisms not clarified	Long COVID (approximately 45% at 1 year) is linked to persistent dysbiosis marked by depletion of SCFA-producing commensals, correlating with impaired quality of life, anxiety/depression, and immune dysregulation, supporting gut-lung and gut-brain axis involvement
Ishizaka et al[122], 2024	56 total, PLWH-CoV: 12 (mild: 7; moderate/severe: 5), PLWH controls: 25, HCs: 19	16S rRNA sequencing	Acute: Enterococcus faecium. Recovery (1-3 months): Roseburia, Lachnospiraceae_unclassified, Faecalibacterium prausnitzii, Eubacterium rectale. Recovered vs long COVID: Prevotella spp.	Acute vs HC: Roseburia, Lachnospiraceae_unclassified. Long COVID vs recovered: Prevotella spp.	Small sample size (n = 12 PLWH-CoV, only 2 PASC); no pre-infection baseline; diet, ART regimens, and variant effects not analyzed	SARS-CoV-2 in PLWH causes persistent dysbiosis, marked by loss of SCFA-producers and enrichment of pathogens, with severity-linked delays in microbiome recovery and risk of PASC
Brīvība et al[123], 2024	146 COVID-19 patients (92 hospitalized, 54 ambulatory) vs 110 HCs	Shotgun metagenomics	Enterococcus faecium, Bacteroides spp., Alistipes, Enterobacteriaceae	Roseburia, Faecalibacterium prausnitzii, Lachnospiraceae, Eubacterium rectale, Prevotella spp.	High antibiotic use; heterogeneous sampling timing; phenotypic heterogeneity across patient groups	Acute COVID-19 shows reduced diversity with loss of butyrate producers; recovery involves their restoration, while Prevotella may protect against long COVID
Sorokina et al[124], 2023	39 post-COVID-19 patients before and after 14-day rehabilitation vs 48 healthy volunteers	Clinical questionnaires, CT; CBC, coagulation, biochemistry; serum IL-6, NSE (ECL); metabolites (GC-MS); microbiota (RT-PCR, colonoflor-16 kit)	Bacteroides spp., Escherichia coli, Enterobacter spp., Staphylococcus aureus, IL-6, succinic acid, fumaric acid, 4-hydroxybenzoic acid	Lactobacillus spp., Bifidobacterium spp., Faecalibacterium prausnitzii, Phenylpropionic acid	Small cohort; no untreated controls; RT-PCR instead of sequencing; limited GI symptom assessment; diet confounded results	Post-COVID-19 is marked by persistent dysbiosis (loss of SCFA-producers, enrichment of pathobionts) and sustained inflammatory/metabolic disturbances not resolved by standard rehabilitation, highlighting the need for personalized microbiome-targeted interventions
Tkacheva et al[125], 2023	178 post-COVID-19 patients: Asymptomatic (A, n = 48), non-infected contacts (N, n = 46), severe (S, n = 86)	16S rRNA sequencing	RF39 (order), Clostridia UCG-014, Oscillospirales UCG-010, Akkermansia, Prevotellaceae (family), Lactobacillus, Romboutsia, Ruminococcus gnavus, Erysipelatoclostridium	Parasutterella, Flavonifractor, Ruminococcus gnavus, Subdoligranulum, Methanobrevibacter, Lachnospiraceae UCG-010, Lachnospiraceae NK4A136, Barnesiella, Eubacterium xylanophilum, Eubacterium siraeum	Cross-sectional (3 months only); no acute phase data; diet/medications not controlled; 16S lacks functional resolution	No major post-COVID microbiome differences by infection/severity at 3 months, but taxa correlated with immune, cardiovascular, and metabolic parameters, highlighting systemic associations beyond direct viral effects
Bredon et al[126], 2025	200 COVID-19 patients vs 102 HCs (Morocco & France cohorts)	Shotgun metagenomic sequencing, machine learning, metabolomics (tryptophan)	Ruminococcus gnavus, Klebsiella pneumoniae, K. variicola, Bacteroides ovatus, Enterococcus; ↑ L-tryptophan biosynthesis	Faecalibacterium prausnitzii, Roseburia spp., Bifidobacterium longum, Dysosmobacter welbionis, Coprococcus comes (SCFA-producers)	Treatment heterogeneity (antibiotics) in the French cohort; ML model not transferable; causality not established	COVID-19 induces gut dysbiosis with depletion of SCFA-producers and enrichment of pathobionts, alongside altered tryptophan metabolism. Dysbiosis correlates with disease severity; the ML model predicted severity in the Moroccan cohort

COVID: Coronavirus disease; COVID-19: Coronavirus disease 2019; MAG: Metagenome-assembled genome; VF: Virulence factor; ARG: Antibiotic resistance gene; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; NC: No coronavirus disease 2019; ITS: Internal transcribed spacer; CT: Computed tomography; SCFA: Short-chain fatty acid; PLWH-CoV: Severe acute respiratory syndrome coronavirus 2-infected people living with human immunodeficiency virus; PLWH: People living with human immunodeficiency virus; HC: Healthy control; PASC: Post-acute sequelae of coronavirus disease 2019; ART: Antiretroviral therapy; CBC: Complete blood count; IL: Interleukin; NSE: Neuron-specific enolase; ECL: Electrochemiluminescence; GC-MS: Gas chromatography-mass spectrometry; RT-PCR: Reverse-transcription polymerase chain reaction; GI: Gastrointestinal; ML: Machine learning.

Table 5 Therapeutic effects of probiotic supplementation on infectious disease outcomes

Probiotic/strain	Virus	Model	Individuality	Mechanism against viral infection	Ref.
Lactobacillus casei 393	HIV-1 (pseudovirus)	In vitro (TZM-bl cells)	HIV-infected adults	Expresses CD4; binds HIV-1 pseudovirus; ↓ infection approximately 60%-70%	[138]
Lactobacillus rhamnosus GR-1 and L. reuteri RC-14	HIV	Clinical (24 adult women)	HIV-infected women	Resolved diarrhea; ↑/stable CD4 in 11/12 vs 3/12 control	[139]
Lactobacillus acidophilus ATCC 4356 engineered with human CD4 (in yogurt)	HIV-1	In vitro & humanized BLT mice	HIV-infected women (Nigeria)	Surface CD4 binds HIV gp120; blocks viral entry	[140]
Lactobacillus casei Shirota (in fermented milk)	HIV	Clinical (children, n = 60)	HIV-infected Vietnamese children	↑ CD4+, Th2, Th17; ↓ Tregs, CD8+ activation; ↓ viral load	[141]
Lactobacillus casei Shirota	EBV, CMV (herpesviruses)	Clinical (athletes)	Healthy athletes	↓ Plasma EBV and CMV IgG titres in seropositive individuals suggest improved immune control of viral reactivation	[142]
Lactobacillus rhamnosus GG	Rotavirus, Cryptosporidium	Clinical (children)	Children with gastroenteritis	Improved intestinal barrier function (↓ L:M ratio); ↑ serum IgG (rotavirus); ↓ reinfection rates in rotavirus-positive children	[143]
Lactobacillus casei Shirota	Norovirus	Clinical (elderly)	Older adults in a care facility	Shortened fever duration; modulated gut microbiota (↑ Lactobacillus, Bifidobacterium; ↓ Enterobacteriaceae); ↑ acetic acid	[144]
Lactobacillus rhamnosus GG	Rhinovirus	Clinical (infants)	Preterm infants (32-36 weeks)	↓ RTI incidence, ↓ rhinovirus infections; no effect on severity or shedding	[145]
Enterococcus faecium NCIMB 10415	Swine influenza A (H1N1, H3N2)	In vitro (cell culture)	Porcine macrophage and epithelial cells	↓ Virus titers (up to 4-log); ↑ cell viability; ↑ NO release; ↓ TNF-α, IL-6, TLR3; ↑ IL-10, IFN-α; direct virus trapping by bacteria	[146]
Bifidobacterium longum BB536	Influenza	Clinical (elderly)	Elderly (mean age 86.7 years)	↓ Influenza and fever incidence, ↑ NK cell activity and neutrophil bactericidal activity; maintained innate immunity	[147]
Bifidobacterium adolescentis SPM0212	HBV	In vitro (HepG2.2.15 cells)	Human hepatocyte-derived cell line	↓ HBsAg and extracellular HBV DNA; ↑ MxA, STAT1 expression via IFN pathway; active antiviral components < 30 kDa	[148]
Bifidobacterium lactis DSM 32246, Bifidobacterium lactis DSM 32247, Lactobacillus acidophilus DSM 32241, Lactobacillus brevis DSM 27961, Lactobacillus helveticus DSM 322426	SARS-CoV-2	Clinical (hospitalized)	Hospitalized COVID-19 patients (Italy, n = 70)	↓ Progression to respiratory failure; ↑ symptom resolution (fever, diarrhea, dyspnea); ↓ ICU admission and mortality; modulation of gut-lung axis; potential ↑ Nrf2/HO-1 antiviral pathways	[149]
Lactobacillus gasseri SBT2055	RSV	In vivo and in vitro	BALB/c mice and HEp-2 cells	↓ RSV titer; ↓ IL-6, TNF-α, IL-1β, CCL2; ↑ IFN-β, IFN-γ, OAS1a, ISG15; ↓ SRCAP expression linked to RSV replication	[150]

HIV: Human immunodeficiency virus; BLT: Bone marrow-liver-thymus; Th: T helper; Tregs: Regulatory T cells; EBV: Epstein-Barr virus; CMV: Cytomegalovirus; IgG: Immunoglobulin G; L:M: Lactulose:mannitol; RTI: Respiratory tract infection; TNF: Tumor necrosis factor; IL: Interleukin; TLR: Toll-like receptor; IFN: Interferon; NK: Natural killer; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; MxA: Myxovirus protein A; STAT1: Signal transducer and activator of transcription 1; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; ICU: Intensive care unit; Nrf2: Nuclear factor erythroid 2-related factor 2; HO-1: Heme oxygenase-1; RSV: Respiratory syncytial virus; CCL2: C-C motif ligand 2; OAS1a: Oligoadenylate synthetase 1a; ISG15: Interferon-stimulated gene product 15.