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Effects of Short-Chain Fatty Acid Combinations Relevant to the Healthy and Dysbiotic Gut upon Candida albicans

Summary

Short-chain fatty acids produced by healthy gut bacteria appear to slow the growth and reduce the invasive characteristics of Candida albicans, a fungus that normally lives harmlessly in the gut but can cause infections when the microbiota is disrupted by antibiotics. This study tested whether healthy gut SCFA levels inhibit Candida more effectively than dysbiotic levels and found that the healthy SCFA mix was somewhat more effective at preventing fungal hyphal formation, which is important for tissue invasion. However, different Candida strains responded differently to the SCFAs, suggesting that individual variation affects how protective these bacterial metabolites can be.

Background

Candida albicans exists as a commensal in the gastrointestinal tract of healthy humans but increases colonization during gut dysbiosis when microbiota and short-chain fatty acid (SCFA) concentrations become perturbed. Individual SCFAs (acetic, propionic, and butyric acids) are known to exert differential effects on C. albicans, but the fungus is generally exposed to combinations of these compounds in vivo.

Objective

To test whether SCFA combinations at concentrations that reflect healthy and dysbiotic gut profiles differentially influence virulence-related phenotypes in C. albicans, including growth, morphogenesis, cell wall stress resistance, and immune recognition patterns.

Results

Both healthy and dysbiotic SCFA mixes slowed C. albicans growth and increased resistance to SDS and caspofungin but reduced thermal stress resistance. The healthy SCFA mix inhibited hyphal development more effectively than the dysbiotic mix in some isolates, though few other differential effects were observed between the two mixes. Most SCFA effects were strain-specific, with minimal impact on adhesion or virulence in the Galleria model.

Conclusion

SCFA mixtures reflecting those present in the human gut subtly influence some virulence-related phenotypes in C. albicans in a strain-specific manner, with the healthy SCFA mix showing greater inhibition of hyphal development that may reduce competitiveness in the healthy gut, though effects on adhesion and systemic virulence were not observed.
  • Published in:Current Microbiology,
  • Study Type:Experimental In Vitro and In Vivo Study,
  • Source: PMID: 40730669, DOI: 10.1007/s00284-025-04400-0
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