AUTHOR=Guo Ying , Lin Lu , Zhang Miao , Yu Yixi , Wang Yan , Cao Jie , Li Yuchen , Sun Xintong , Guan Meilin , Wen Shuo , Wang Xin , Fang Zhen , Duan Wenshan , Duan Junyi , Huang Tao , Xia Wei , Guo Shan , Wei Feili , Zheng Dongxiang , Huang Xiaojie TITLE=Salivary mycobiome alterations in HIV-infected MSM: dominance of Pseudogymnoascus and functional shifts across disease stages JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1564891 DOI=10.3389/fcimb.2025.1564891 ISSN=2235-2988 ABSTRACT=BackgroundOral health is increasingly recognized as a crucial determinant of overall health in people living with HIV/AIDS (PLWHA). Specifically, the oral mycobiome may play a pivotal role in HIV-associated oral complications. However, the fungal species involved and their potential as biomarkers for HIV-related oral conditions remain poorly understood. This study investigates salivary fungal profiles in PLWHA who have sex with men (MSM), focusing on diversity, functional shifts, and correlations with disease progression.MethodsA cross-sectional study included 25 MSM participants divided into five groups: HIV-negative controls (n = 5) and four HIV-positive groups stratified by CD4 count: Stage 0 (HIV RNA-positive/antibody-negative; n = 5), Stage 1 (CD4 ≥500 cells/μL; n = 5), Stage 2 (CD4 200–499 cells/μL; n = 5), and Stage 3 (CD4 <200 cells/μL or opportunistic infections; n = 5). Saliva samples were collected and analyzed using metagenomic sequencing (Illumina NovaSeq platform). Bioinformatic analyses included genome assembly (MEGAHIT), gene clustering (CD-HIT), gene abundance calculation (SOAPaligner), species annotation (BLASTP), and KEGG pathway annotation (KOBAS 2.0). Statistical analyses (Kruskal-Wallis tests, Spearman’s correlation) assessed associations between fungal profiles, CD4 count, and viral loads.ResultsA total of 51 fungal genera were identified, with Pseudogymnoascus being the most abundant. Functional analysis revealed 113 shared KEGG pathways, of which 69 were unique to Stage 3, primarily related to metabolic and disease-related processes. Notably, Auricularia exhibited a positive correlation with CD4 count (P ≤ 0.01), while Mucor showed a negative correlation (P = 0.0299).ConclusionsSalivary mycobiome composition and function shift significantly across HIV stages, reflecting immune decline. Pseudogymnoascus dominance challenges conventional views of oral fungal ecology in immunocompromised hosts. These findings highlight the mycobiome’s diagnostic potential for monitoring HIV-related oral health. Longitudinal studies are needed to validate clinical relevance.