Abstract
In HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.
Highlights
In HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects
Viral loads in the nucleoside reverse transcriptase inhibitor (NRTI)(+) group declined to an undetectable level (20 copies/mL) by 24 weeks after ART initiation, whereas those in the NRTI(–) groups were undetectable or close to the undetectable level for 24 weeks
It has not been fully understood whether different ART regimens have any distinct impacts on the intestinal and oral microbiotas and, if any, how the regimen changes the microbial composition over time
Summary
In HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. We observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. In vitro studies have indicated that an NRTI, zidovudine (AZT), exhibits antibacterial effects[21] likely due to inhibition of bacterial polymerases and/ or induction of the SOS DNA damage r esponse[22,23,24,25] This evidence indicates that the gut microbiota of HIV1-infected patients may be linked to gastrointestinal defects even under short-term ART. We analyzed the potential effects of different regimens on the gut and oral microbial populations over time
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