Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV

Background : The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we have explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Methods : Fecal and salivary samples were collected from PLWH (n=69) and healthy controls (HC, n=80). DNA was extracted for 16S rRNA sequencing on the MiSeq platform. The obtained raw reads were pre-processed, and taxonomy analysis was performed to determine the microbial composition. Additionally, linear discriminant analysis effect size and correlation analyses were used to identify differences in abundant taxa and relationship between microbial abundance and ART regimens, BMI, CD4 ⁺ T-cell count, CD4/CD8 ratio, and duration of ART. Results : We found that the PLWH had significantly lower richness compared to HC in both the oral and gut environment. Interestingly, the gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium , whereas non-nucleotide reverse transcriptase inhibitor (NNRTI) treated individuals were enriched with Gordonibacter , Megasphaera, and Staphylococcus . In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Conclusion : Our study revealed significant shifts in bacterial diversity and composition between HC and PLWH in both the oral and gut environments. Additionally, we also detected specific microbial signatures, which were correlated with different treatment regimens and BMI among the PLWH under successful ART.