Salivary Mycobiome Alterations in HIV-Infected MSM: Dominance of Pseudogymnoascus and Functional Shifts Across Disease Stages

Ying Guo^1,2Lu Lin¹Miao Zhang¹Yixi Yu¹Wang Yan¹Jie Cao¹Li Yuchen¹Xintong Sun¹Meilin Guan¹Wen Shuo¹Xin Wang¹Zhen Fang³Wenshan Duan³Junyi Duan³Tao Huang³Wei Xia³Shan Guo²Feili Wei²Dongxiang Zheng¹Xiaojie Huang^3*

• ¹Department of Stomatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
• ²Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing City, China
• ³Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China

Background: Oral 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.Methods: A 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.Results: A 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). Conclusions: Salivary 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.