ena-STUDY-University of Tromso-08-04-2019-07:32:53:149-23
16S rRNA amplicon analysis of rectal swab samples form HIV infected children in Zimbabwe
Objective: The gastrointestinal barrier is one of the first targets of HIV infection, with substantial depletion of CD4 cells in the gut. Antiretroviral therapy (ART) restores the CD4 counts and is thought to have beneficial effects on gut microbiota in adults. However, little is known about the effect of long-term ART on gut microbiome in perinatally-infected children. The objective of this study was to evaluate the composition of gut microbiota in HIV infected children and estimate the effect of ART.Design: A cross-sectional study of 177 HIV infected children (149 with chronic lung disease (CLD), 28 without CLD) on ART and 103 HIV uninfected controls enrolled in Harare, Zimbabwe.Methods: Rectal swabs were collected from all participants and the composition of the gut microbiota was explored using 16S rRNA sequencing (Illumina Miseq). Alpha diversity was determined using observed OTUs, Chao1 and Shannon indices. Bray-Curtis dissimilarity index was used to assess beta diversity, and linear discriminant analysis effect size was used to explore relative abundance between groups.Results: HIV infected children had significantly lower alpha diversity and higher beta diversity compared to HIV uninfected. No association was observed between microbiome diversity measures and markers of HIV progression (CD4+ T-cell counts and viral load) or HIV-associated CLD. We found enriched levels of Corynebacterium (p<0.01), Finegoldia (p<0.01) and Anaerococcus (p<0,01) in HIV infected participants, as well as enrichment of Enterobacteriaceae (p=0.02) in participants with low CD4+ T-cell counts (<400 cells/mm3). Finally, prolonged ART-treatment (>10 years) was significantly associated with a richer gut microbiota.Conclusion: HIV infected children have altered gut microbiota. ART restores gut microbiome diversity to levels observed in HIV negative individuals.
Objective: The gastrointestinal barrier is one of the first targets of HIV infection, with substantial depletion of CD4 cells in the gut. Antiretroviral therapy (ART) restores the CD4 counts and is thought to have beneficial effects on gut microbiota in adults. However, little is known about the effect of long-term ART on gut microbiome in perinatally-infected children. The objective of this study was to evaluate the composition of gut microbiota in HIV infected children and estimate the effect of ART.Design: A cross-sectional study of 177 HIV infected children (149 with chronic lung disease (CLD), 28 without CLD) on ART and 103 HIV uninfected controls enrolled in Harare, Zimbabwe.Methods: Rectal swabs were collected from all participants and the composition of the gut microbiota was explored using 16S rRNA sequencing (Illumina Miseq). Alpha diversity was determined using observed OTUs, Chao1 and Shannon indices. Bray-Curtis dissimilarity index was used to assess beta diversity, and linear discriminant analysis effect size was used to explore relative abundance between groups.Results: HIV infected children had significantly lower alpha diversity and higher beta diversity compared to HIV uninfected. No association was observed between microbiome diversity measures and markers of HIV progression (CD4+ T-cell counts and viral load) or HIV-associated CLD. We found enriched levels of Corynebacterium (p<0.01), Finegoldia (p<0.01) and Anaerococcus (p<0,01) in HIV infected participants, as well as enrichment of Enterobacteriaceae (p=0.02) in participants with low CD4+ T-cell counts (<400 cells/mm3). Finally, prolonged ART-treatment (>10 years) was significantly associated with a richer gut microbiota.Conclusion: HIV infected children have altered gut microbiota. ART restores gut microbiome diversity to levels observed in HIV negative individuals.