Background A growing body of literature connects the gut mycobiota to several diseases, including HIV infection. In contrast to bacteria, fungi represent a smaller fraction of the gut microbiota and pose several technical challenges, including low biomass, environmental contamination and primer-associated biases. Characterizing the gut mycobiota in HIV infection is still at an early stage. Methods We characterized the gut mycobiota in untreated people living with HIV (PWH, n = 69), PWH on antiretroviral therapy (PWHA) for at least 2 years (n = 14) and people without HIV (PWoH, n = 48) using ITS1 sequencing, which preferentially detects certain fungal taxa such as Candida. Associations with immune status (CD4 count), fungal (1,3-β-D-glucan) and bacterial translocation (soluble CD14), monocyte activation (sCD163) and epithelial integrity (intestinal fatty acid binding protein, I-FABP) were assessed. Analyses included diversity metrics, differential abundance, and correlations, acknowledging potential residual confounders. Results Fungal diversity (richness and Shannon index) did not differ significantly between groups, although PWH with CD4 ≥ 200 cells/µL showed values closer to PWHA and PWoH. Immune status explained a small but significant proportion of the variance in fungal composition (6.2%, P = 0.002). The gut mycobiota was dominated by Candida (18.6%), Aspergillus (18.2%), Rhodotorula (11.5%), Penicillium (8.1%), and Saccharomyces (7.5%), taxa that might partly reflect dietary or environmental exposures. Four enterotypes, dominated by Aspergillus, Saccharomyces, Rhodotorula, and Candida were identified; the Candida-dominated enterotype was less diverse (P < 0.01), observed only in PWH, and associated with lower CD4 counts and higher sCD163 levels. Consistently, Candida relative abundance was inversely correlated with CD4 counts, CD4/CD8 ratio, and positively with sCD163. Enterotype stratification did not reveal consistent associations with other host metadata. Circulating 1,3-β-D-glucan levels did not differ between groups. Conclusions HIV infection and immune status are associated with specific fungal signatures, including a Candida-dominated enterotype linked to CD4 counts and monocyte activation, although overall effects are modest relative to high inter-individual variability. Interpretation is limited by residual confounding, particularly diet and environmental exposures, ITS1-related biases, and cohort composition enriched for advanced HIV. These findings support the need for integrative, longitudinal studies to clarify the role of the gut mycobiota in HIV.

Limited impact of HIV infection and immune status on the gut mycobiota

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2026年4月24日

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Monserrat Chávez-Torres,
Amy Peralta-Prado,
Santiago Ávila-Ríos,
Karla Romero-Mora,
Sandra M. Pinto-Cardoso

摘要

Background

A growing body of literature connects the gut mycobiota to several diseases, including HIV infection. In contrast to bacteria, fungi represent a smaller fraction of the gut microbiota and pose several technical challenges, including low biomass, environmental contamination and primer-associated biases. Characterizing the gut mycobiota in HIV infection is still at an early stage.

Methods

We characterized the gut mycobiota in untreated people living with HIV (PWH, n = 69), PWH on antiretroviral therapy (PWHA) for at least 2 years (n = 14) and people without HIV (PWoH, n = 48) using ITS1 sequencing, which preferentially detects certain fungal taxa such as Candida. Associations with immune status (CD4 count), fungal (1,3-β-D-glucan) and bacterial translocation (soluble CD14), monocyte activation (sCD163) and epithelial integrity (intestinal fatty acid binding protein, I-FABP) were assessed. Analyses included diversity metrics, differential abundance, and correlations, acknowledging potential residual confounders.

Results

Fungal diversity (richness and Shannon index) did not differ significantly between groups, although PWH with CD4 ≥ 200 cells/µL showed values closer to PWHA and PWoH. Immune status explained a small but significant proportion of the variance in fungal composition (6.2%, P = 0.002). The gut mycobiota was dominated by Candida (18.6%), Aspergillus (18.2%), Rhodotorula (11.5%), Penicillium (8.1%), and Saccharomyces (7.5%), taxa that might partly reflect dietary or environmental exposures. Four enterotypes, dominated by Aspergillus, Saccharomyces, Rhodotorula, and Candida were identified; the Candida-dominated enterotype was less diverse (P < 0.01), observed only in PWH, and associated with lower CD4 counts and higher sCD163 levels. Consistently, Candida relative abundance was inversely correlated with CD4 counts, CD4/CD8 ratio, and positively with sCD163. Enterotype stratification did not reveal consistent associations with other host metadata. Circulating 1,3-β-D-glucan levels did not differ between groups.

Conclusions

HIV infection and immune status are associated with specific fungal signatures, including a Candida-dominated enterotype linked to CD4 counts and monocyte activation, although overall effects are modest relative to high inter-individual variability. Interpretation is limited by residual confounding, particularly diet and environmental exposures, ITS1-related biases, and cohort composition enriched for advanced HIV. These findings support the need for integrative, longitudinal studies to clarify the role of the gut mycobiota in HIV.