biostudies-literatureOrtiz AMIntramural NIH HHS112020https://www.ebi.ac.uk/biostudies/studies/S-EPMC9989505biostudies-literatureUnknown42(1)Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (T_H17) and T_H22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier.Cell reportsExperimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility.PMC9989505Z99 AI999999Z01 AI001029Flynn JKBaker PJBrenchley JMLangner CAVinton CLKeele BFSimpson JStarke CEBelkaid YStacy AFennessey CMOrtiz AMfalseExperimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility.Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (T_H17) and T_H22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier.2023-01-01T00:00:00Z2023 Jan2024-11-11T18:59:56.405Z2024-11-11T18:59:56.405ZS-EPMC99895053684823010.1016/j.celrep.2023.112020