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

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.