Journal Article Epublish 1 citation
PubMed: 40098016 DOI: 10.1186/s40249-025-01291-y
Gut microbiota metabolites impact immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men.
Infect Dis Poverty 14(1):21
Authors: Anping Feng, Heping Zhao, Chunting Qiu, Dan Luo, Hao Wu, Xiaojun Meng, Linghua Li, Huachun Zou
Affiliations
- School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
- School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, China. Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, No 8 Huaying Road, Guangzhou, 510060, Guangdong, China.
- Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, 300192, China.
- Guangzhou Center for Disease Control and Prevention, Guangzhou, China.
- The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi, 214023, Jiangsu, China.
- Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, No 8 Huaying Road, Guangzhou, 510060, Guangdong, China.
- School of Public Health, Fudan University, Room 435, Bld #8, 130 Dongan Road, Xuhui District, Shanghai, 200032, China. School of Public Health, Southwest Medical University, Luzhou, China. Kirby Institute, University of New South Wales, Sydney, Australia.
Abstract
BACKGROUND
The association between gut microbial metabolites and immunologic non-response among people living with HIV (PLHIV) receiving antiretroviral therapy (ART) has not been well established. We aimed to characterize gut microbial metabolites among HIV-infected men who have sex with men (MSM) with different immunologic responses.
METHODS
We recruited HIV-infected MSM from Guangzhou Eighth People's Hospital and HIV-uninfected MSM (healthy controls, HC) from a local MSM community-based organization in Guangzhou between June and October 2021. HIV-infected MSM were grouped into good immunological responders (GIR) (CD4 + T cell count ≥ 350 cells/μl) and poor immunological responders (PIR) (CD4 + T cell count < 350 cells/μl) after 24 months of ART treatment. Online questionnaires and stool samples were collected. Microbial metabolites in stool were obtained through ultra-performance liquid chromatography coupled to a tandem mass spectrometry (UPLC-MS/MS) system. Differential metabolites were identified and analyzed using the Kruskal-Wallis test, followed by pairwise comparisons with the Wilcoxon rank-sum test. The least absolute selection and shrinkage operator was used to select potential metabolites biomarkers.
RESULTS
A total of 51 HC, 56 GIR, and 42 PIR were included. No statistically significant differences were observed in the median time since HIV diagnosis and ART duration between GIR and PIR. Among the 174 quantified metabolites, 81 significantly differed among HC, GIR, and PIR (P < 0.05). Among differential metabolites, indole-3-propionic acid significantly decreased from HC (11.39 nmol/g) and GIR (8.16 nmol/g) to PIR (6.50 nmol/g). The pathway analysis showed that tryptophan metabolism differed significantly between GIR and PIR (P < 0.05). Four potential metabolites biomarkers (dimethylglycine, cinnamic acid, 3-hydroxyisovaleric acid, and propionic acid) that distinguish GIR and PIR were identified, and the corresponding area under the curve based on potential biomarkers was 0.773 (95% CI: 0.675-0.871).
CONCLUSIONS
This study identified significant differences in gut microbial metabolites among HIV-infected MSM with different immunologic responses. These results indicate the potential of gut microbial metabolites as novel disease progression markers and therapeutic targets.
MeSH
Cells, Biomarkers, Sex, Cell Count, Therapeutics, Gastrointestinal Microbiome, Microbiota