IN a new study that challenges conventional assumptions about gut health in people living with HIV, researchers have found that sexual behavior has a stronger association with gut microbiome composition than either antiretroviral therapy (ART) regimens or weight changes. The findings highlight the need for enterotype-based approaches when analyzing gut microbiota in this population.
The study, involving 118 people living with HIV, used 16S rRNA gene sequencing to analyze gut bacteria and categorized participants by microbial enterotype—either Prevotella or Bacteroides-dominated. Remarkably, sexual orientation emerged as the strongest correlate of enterotype. Of the individuals with a Prevotella-dominated gut profile, 93% were men who have sex with men (MSM), while the Bacteroides-dominated group included just 31% MSM.
Differences between MSM and non-MSM groups extended to 49 bacterial genera, making sexual orientation the dominant influence on gut microbiome composition. In contrast, weight gain after an ART switch was associated with just six bacterial taxa, five of which were exclusive to Bacteroides-dominated individuals. Among these, Actinobacteria and Bifidobacterium stood out in those who gained more than 5% of their body weight over a year.
Further distinctions emerged when comparing individuals with extreme weight changes: those with ≥6.3% gain and ≤3.19% loss. Only three bacterial phyla—Firmicutes, Verrucomicrobia, and Synergistetes—were significantly different between these two groups. Functional analysis also revealed that glycan and lipid metabolism pathways were tied to weight gain, but only in Bacteroides-dominated individuals.
Interestingly, ART regimen-related microbiota changes were limited to individuals in the Prevotella group, specifically involving the Actinobacteria phylum.
These findings suggest that while ART and weight gain can influence gut microbiota, their impact is relatively minor compared to sexual behavior-driven differences. Stratifying patients by enterotype may help clinicians identify microbiome alterations more precisely and potentially tailor interventions for weight and metabolic management in HIV care.
Reference:
Kehrmann J et al. Gut microbiota differences linked to weight gain and ART in people living with HIV are enterotype specific and minor compared to the large differences linked to sexual behavior. Front Cell Infect Microbiol. 2025;15:1568352.
