Table 3.

Bacterial and fungal metabolites against cancer and virus infections

Metabolite type	Sources	Antiviral and anticancer mechanisms	Key evidence and outcomes	References
Bacterial metabolites
Short-Chain Fatty Acids (SCFAs) (Examples: Acetate, Propionate, Butyrate)	Antiviral: Bifidobacterium, Faecalibacterium, Roseburia Anticancer: Bifidobacterium, Faecalibacterium, Roseburia	Antiviral: Activate GPR43/41 to promote type I IFN and ISG expression in lung epithelial cells, reducing viral load. Regulate inflammation via HDAC inhibition and NLRP3 inflammasome modulation. Enhance IgA secretion and Treg differentiation for mucosal protection. Anticancer: Inhibit HDACs to induce apoptosis and cell cycle arrest (G2/M phase). Enhance CD8 + T-cell function and DC maturation via GPR109A. - Reduce inflammation and tumor angiogenesis.	Antiviral: Acetate protects against rotavirus (RV) and respiratory syncytial virus (RSV) by GPR43-mediated IFN responses; high-fiber diets increase SCFA production, reducing RV load and inflammation in animal models. Butyrate limits influenza A virus (IAV) replication by priming myeloid cells for antiviral hematopoiesis. Dual effects: Low SCFAs may promote viral persistence in dysbiosis. Anticancer: Butyrate suppresses CRC proliferation via p53 activation; high SCFA levels correlate with better ICI response in melanoma. Dual effects: High systemic SCFAs may limit CTLA-4 blockade efficacy by Treg induction.	[27, 104, 137, 138]
Flavonoid Derivatives (Examples: Desaminotyrosine (DAT))	Antiviral: Clostridium orbiscindens Anticancer: ???	Antiviral: Enhances type I IFN signaling in macrophages via TLR7/9, protecting against influenza. Modulates distal lung immunity through gut-lung axis. Anticancer: ???	Antiviral: DAT from gut commensals reduces influenza severity in mice; antibiotic depletion abolishes protection. Proviral in some contexts (e.g., enhances enteric norovirus stability). Anticancer: ???	[27]
Bile Acids (Examples: Secondary bile acids (e.g., deoxycholic acid, lithocholic acid))	Antiviral: Clostridium, Bacteroides Anticancer: Clostridium scindens	Antiviral: Activate FXR/TGR5 receptors to regulate IFN responses and inflammasomes. Inhibit viral entry/replication in some viruses (e.g., norovirus). Anticancer: FXR activation inhibits proliferation; UDCA reduces inflammation. Modulate Tregs/Th17 balance to suppress tumor growth.	Antiviral: Bile acids from microbiota inhibit murine norovirus via FXR signaling; dysbiosis reduces this protection. Dual role: Some promote inflammation aiding viral spread in chronic infections. Anticancer: Secondary bile acids like DCA promote CRC at high levels but UDCA protects via FXR in HCC models.	[27, 104, 137, 138]
Tryptophan Metabolites (Examples: Indole, Indole-3-propionic acid (IPA))	Antiviral: Clostridium sporogenes, Bacteroides Anticancer: Lactobacillus reuteri, Clostridium	Antiviral: Activate AhR to enhance epithelial barrier and IL-22 production, limiting viral invasion. Modulate NLRP6 inflammasome for antiviral innate immunity. Anticancer: Activate AhR to boost IL-22 and barrier integrity, inhibiting tumor invasion. Enhance CD8 + T-cell infiltration and ICI efficacy.	Antiviral: Indole derivatives protect against influenza by boosting IFN-γ and Treg cells; microbiota depletion impairs this. Anticancer: IPA from Lactobacillus improves PD-1 blockade in CRC models; low IPA linked to poor prognosis. I3A restores mucosal integrity in liver fibrosis models.	[104, 137, 138]
Other Metabolites (Examples: Inosine, TMAO)	Antiviral: ??? Anticancer: Bifidobacterium pseudolongum	Antiviral: ??? Anticancer: Inosine via A2A receptor enhances T-cell priming for ICI synergy. TMAO promotes antitumor immunity in breast cancer via IFN-γ.	Antiviral: ??? Anticancer: Inosine boosts PD-1 efficacy in multiple cancers; Bifidobacterium colonization correlates with better outcomes.	[27]
Fungal metabolites
Polysaccharides	Antiviral: Ganoderma spp: HSV, Influenza Anticancer: ???	Antiviral: Immune modulation, viral attachment inhibition Anticancer: ???	Antiviral: Hinnuliquinone from fungal sources inhibits HIV-1 protease. Agrocybone from Agrocybe salicacola shows activity via inhibition of viral hemagglutinin. Anticancer: ???	[142, 143]
Cordycepin	Antiviral: Cordyceps militaris: SARS-CoV-2 Anticancer: ???	Antiviral: Mpro inhibition, poly(A) polymerase blockade Anticancer: ???	Antiviral: Sphaeropsidins A and B from phytopathogenic fungi reduce bovine coronavirus yield by deacidifying lysosomes and downregulating aryl hydrocarbon receptor signaling. Anticancer: ???	[142, 143]
Sphaeropsidins A/B	Antiviral: Diplodia spp: Bovine coronavirus Anticancer: ???	Antiviral: Lysosomal deacidification, AhR downregulation Anticancer: ???	Antiviral: ??? Anticancer: ???	[142, 143]
Hinnuliquinone	Antiviral: fungal dimeric non-peptide: HIV-1 Anticancer: ???	Antiviral: Protease inhibition Anticancer: ???	Antiviral: ??? Anticancer: ???
Ganoderic acids	Antiviral: ??? Anticancer: Ganoderma lucidum: Hepatocellular carcinoma	Antiviral: ??? Anticancer: ROS induction, apoptosis	Antiviral: ??? Anticancer: ???	[142, 143]
Pestheic acid	Antiviral: ??? Anticancer: Pestalotiopsis guepinii: Hepatocellular carcinoma	Antiviral: ??? Anticancer: Cytostatic, genotoxic	Antiviral: HSV, Influenza Anticancer: ???	[142, 143]
Simplicilliumtides	Antiviral: ??? Anticancer: Simplicillium obclavatum: Gastric adenocarcinoma	Antiviral: ??? Anticancer: Cytotoxicity (IC50 39–100 µM)	Antiviral: ??? Anticancer: ???	[142, 143]
Beauvericins	Antiviral: ??? Anticancer: Fusarium spp: Leukemia (HL-60, K562)	Antiviral: ??? Anticancer: Mycotoxic, pathway modulation	Antiviral: ??? Anticancer: ???	[142, 143]