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

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.