Host-Pathogen Interactions in Gastrointestinal Fungal Colonization

The gastrointestinal tract represents a complex ecological niche where opportunistic fungi, most notably Candida species, coexist with a diverse microbial community and a multilayered host defence system. In health, commensalism prevails through balanced microbial interactions, intact mucosal barriers and finely tuned immune responses. Disruption of this balance—whether by antibiotic‐induced dysbiosis, mucosal damage or immunosuppression—can trigger fungal morphological switching from yeast to invasive hyphae, leading to increased adhesion, biofilm formation and translocation across the epithelium. Host factors, including genetic polymorphisms in innate immune sensors and cytokine pathways, further modulate fungal burden and inflammatory tone. At the same time, microbial‐derived metabolites such as short‐chain fatty acids not only maintain epithelial integrity but also directly inhibit fungal growth and morphogenesis. Understanding these bidirectional interactions is critical for devising strategies to prevent fungal overgrowth, safeguard mucosal integrity and avert systemic dissemination, with implications for probiotic therapies, targeted immunomodulation and precision antibiotic stewardship.

Research from Nature Portfolio

Integration of transcriptional and metabolic profiling in epithelial co‐culture systems has revealed that Lactobacillus rhamnosus reshapes the gut environment by consuming key nutrients and releasing antivirulence compounds, thereby forcing Candida albicans into metabolic states that diminish hyphal formation and invasive potential. Complementary work has demonstrated that treatment with β‐lactam antibiotics provokes a “peptidoglycan storm” as commensal bacteria release cell‐wall fragments, which act as potent inducers of fungal hyphal growth, converting a normally restrictive niche into one that favours tissue invasion and systemic spread. Earlier mechanistic studies established that antibiotic‐induced depletion of microbial‐derived short‐chain fatty acids correlates with elevated fungal loads in vivo and that physiological concentrations of acetate, propionate and butyrate directly inhibit C. albicans germ‐tube formation, hyphal development and biofilm assembly in vitro.

Host-Pathogen Interactions in Gastrointestinal Fungal Colonization publication trend

The graph below shows the total number of articles in host-pathogen interactions in gastrointestinal fungal colonization across all publications each year (not limited to Nature Index journals).

Technical terms

Commensalism: A symbiotic relationship in which a microorganism resides within the host without causing harm.

Dysbiosis: A perturbation of the normal microbial community structure that can impair host health.

Short‐chain fatty acids (SCFAs): Microbial fermentation products (acetate, propionate, butyrate) that support epithelial integrity and modulate fungal behaviour.

Hyphal morphogenesis: The transition of fungal cells from a rounded yeast form to elongated, filamentous hyphae enabling tissue invasion.

Translocation: The movement of microorganisms across the epithelial barrier into underlying tissues or the circulation.

References

1. Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response. Gut Microbes (2023).
2. Candida albicans selection for human commensalism results in substantial within-host diversity without decreasing fitness for invasive disease. PLOS Biology (2023).
3. Interplay between host and Candida albicans during commensal gut colonization. PLOS Pathogens (2023).
4. Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids correlate with increased gastrointestinal colonization of Candida albicans. Scientific Reports (2019).
5. Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity. Nature Communications (2022).
6. A peptidoglycan storm caused by β-lactam antibiotic’s action on host microbiota drives Candida albicans infection. Nature Communications (2021).