Croxford, S. et al. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort. Lancet Public Health 2, e35–e46 (2017).
Fontela, C. et al. Trends and causes of mortality in a population-based cohort of HIV-infected adults in Spain: comparison with the general population. Sci. Rep. 10, 8922 (2020).
Brenchley, J. M. et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J. Exp. Med. 200, 749–759 (2004).
Somsouk, M. et al. Gut epithelial barrier and systemic inflammation during chronic HIV infection. AIDS 29, 43–51 (2015).
Brenchley, J. M. et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12, 1365–1371 (2006).
Dillon, S. M. et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 7, 983–994 (2014).
Ray, S. et al. Altered gut microbiome under antiretroviral therapy: impact of efavirenz and zidovudine. ACS Infect. Dis. 7, 1104–1115 (2021).
Imahashi, M. et al. Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients. Sci. Rep. 11, 960 (2021).
Rocafort, M. et al. HIV-associated gut microbial alterations are dependent on host and geographic context. Nat. Commun. 15, 1055 (2024).
Vos, A. G. et al. Cardiovascular disease burden in rural Africa: does HIV and antiretroviral treatment play a role?: baseline analysis of the Ndlovu Cohort study. J. Am. Heart Assoc. 9, e013466 (2020).
Lozupone, C. A. et al. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe 14, 329–339 (2013).
Mutlu, E. A. et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 10, e1003829 (2014).
Monaco, C. L. et al. Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe 19, 311–322 (2016).
Vujkovic-Cvijin, I. et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci. Transl. Med. 5, 193ra91 (2013).
Vujkovic-Cvijin, I. et al. HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases. Nat. Commun. 11, 2448 (2020).
Borgognone, A. et al. Gut microbiome signatures linked to HIV-1 reservoir size and viremia control. Microbiome 10, 59 (2022).
Vázquez-Castellanos, J. F. et al. Interplay between gut microbiota metabolism and inflammation in HIV infection. ISME J. 12, 1964–1976 (2018).
Guillén, Y. et al. Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection. Mucosal Immunol. 12, 232–246 (2019).
Bai, X. et al. Whole-genome metagenomic analysis of the gut microbiome in HIV-1-infected individuals on antiretroviral therapy. Front. Microbiol. 12, 667718 (2021).
Zhang, Y. et al. Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV. Front. Cell. Infect. Microbiol. 13, 1202035 (2023).
Fulcher, J. A. et al. Gut dysbiosis and inflammatory blood markers precede HIV with limited changes after early seroconversion. EBioMedicine 84, 104286 (2022).
Lu, W. et al. Association between gut microbiota and CD4 recovery in HIV-1 infected patients. Front. Microbiol. 9, 1451 (2018).
Rocafort, M. et al. Evolution of the gut microbiome following acute HIV-1 infection. Microbiome 7, 73 (2019).
Sharifi, F. & Ye, Y. Identification and classification of reverse transcriptases in bacterial genomes and metagenomes. Nucleic Acids Res. 50, e29 (2022).
Plaza Oñate, F. et al. MSPminer: abundance-based reconstitution of microbial pan-genomes from shotgun metagenomic data. Bioinformatics 35, 1544–1552 (2019).
Mallick, H. et al. Multivariable association discovery in population-scale meta-omics studies. PLoS Comput. Biol. 17, e1009442 (2021).
Stražar, M. et al. Gut microbiome-mediated metabolism effects on immunity in rural and urban African populations. Nat. Commun. 12, 4845 (2021).
Tamburini, F. B. et al. Short- and long-read metagenomics of urban and rural South African gut microbiomes reveal a transitional composition and undescribed taxa. Nat. Commun. 13, 926 (2022).
Quevillon, E. et al. InterProScan: protein domains identifier. Nucleic Acids Res. 33, W116–W120 (2005).
Ravcheev, D. A. et al. Comparative genomics and evolution of regulons of the LacI-family transcription factors. Front. Microbiol. 5, 294 (2014).
Stahl, M. L. & Ferrari, E. Replacement of the Bacillus subtilis subtilisin structural gene with an in vitro-derived deletion mutation. J. Bacteriol. 158, 411–418 (1984).
Greenblum, S., Turnbaugh, P. J. & Borenstein, E. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc. Natl Acad. Sci. USA 109, 594–599 (2012).
Jeckelmann, J.-M. & Erni, B. The mannose phosphotransferase system (Man-PTS)—mannose transporter and receptor for bacteriocins and bacteriophages. Biochim. Biophys. Acta Biomembr. 1862, 183412 (2020).
Bourke, C. D. et al. Cotrimoxazole reduces systemic inflammation in HIV infection by altering the gut microbiome and immune activation. Sci. Transl. Med. 11, 486 (2019).
Sandler, N. G. et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J. Infect. Dis. 203, 780–790 (2011).
Wang, Z. et al. Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease. Nat. Commun. 11, 6063 (2020).
von Schillde, M.-A. et al. Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines. Cell Host Microbe 11, 387–396 (2012).
Ladhani, S. Understanding the mechanism of action of the exfoliative toxins of Staphylococcus aureus. FEMS Immunol. Med. Microbiol. 39, 181–189 (2003).
De Filippis, F. et al. Distinct genetic and functional traits of human intestinal Prevotella copri strains are associated with different habitual diets. Cell Host Microbe 25, 444–453.e3 (2019).
Tett, A. et al. The Prevotella copri complex comprises four distinct clades underrepresented in Westernized populations. Cell Host Microbe 26, 666–679.e7 (2019).
Fehlner-Peach, H. et al. Distinct polysaccharide utilization profiles of human intestinal Prevotella copri isolates. Cell Host Microbe 26, 680–690.e5 (2019).
D’Agostino, R. B. et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117, 743–753 (2008).
Braz, V. A., Holladay, L. A. & Barkley, M. D. Efavirenz binding to HIV-1 reverse transcriptase monomers and dimers. Biochemistry 49, 601–610 (2010).
Corso, G., Stärk, H., Jing, B., Barzilay, R. & Jaakkola, T. DiffDock: diffusion steps, twists, and turns for molecular docking. Preprint at https://doi.org/10.48550/arXiv.2210.01776 (2022).
Kieft, K. & Anantharaman, K. Deciphering active prophages from metagenomes. mSystems 7, e0008422 (2022).
Johansen, J. et al. Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. Nat. Microbiol. 8, 1064–1078 (2023).
Johansen, J. et al. Genome binning of viral entities from bulk metagenomics data. Nat. Commun. 13, 965 (2022).
De Paepe, M. et al. Carriage of λ latent virus is costly for its bacterial host due to frequent reactivation in monoxenic mouse intestine. PLoS Genet. 12, e1005861 (2016).
Boling, L. et al. Dietary prophage inducers and antimicrobials: toward landscaping the human gut microbiome. Gut Microbes 11, 721–734 (2020).
Roux, S. et al. Ecology and molecular targets of hypermutation in the global microbiome. Nat Commun. 12, 3076 (2020).
Devoto, A. E. et al. Megaphages infect Prevotella and variants are widespread in gut microbiomes. Nat. Microbiol. 4, 693–700 (2019).
Holmager, T. L. F., Meyrowitsch, D. W., Bahendeka, S. & Nielsen, J. Food intake and cardiometabolic risk factors in rural Uganda. Arch. Public Health 79, 24 (2021).
Kovatcheva-Datchary, P. et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 22, 971–982 (2015).
Iljazovic, A. et al. Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation. Mucosal Immunol. 14, 113–124 (2021).
Pedersen, H. K. et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376–381 (2016).
Blanco-Míguez, A. et al. Extension of the Segatella copri complex to 13 species with distinct large extrachromosomal elements and associations with host conditions. Cell Host Microbe 31, 1804–1819.e9 (2023).
Hersperger, A. R. et al. Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression. Blood 117, 3799–3808 (2011).
Gálvez, E. J. C. et al. Distinct polysaccharide utilization determines interspecies competition between intestinal Prevotella spp. Cell Host Microbe 28, 838–852.e6 (2020).
Arias, C. F., Acosta, F. J., Bertocchini, F., Herrero, M. A. & Fernández-Arias, C. The coordination of anti-phage immunity mechanisms in bacterial cells. Nat. Commun. 13, 7412 (2022).
Bobonis, J. et al. Bacterial retrons encode phage-defending tripartite toxin–antitoxin systems. Nature 609, 144–150 (2022).
Mestre, M. R. et al. UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions. Nucleic Acids Res. 50, 6084–6101 (2022).
Henrot, C. & Petit, M.-A. Signals triggering prophage induction in the gut microbiota. Mol. Microbiol. 118, 494–502 (2022).
Guo, Y. et al. A reverse transcriptase controls prophage genome reduction to promote phage dissemination in Pseudomonas aeruginosa biofilms. Cell Rep. 43, 114883 (2024).
Liu, M. et al. Reverse transcriptase-mediated tropism switching in Bordetella bacteriophage. Science 295, 2091–2094 (2002).
Leeansyah, E. et al. Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. J. Infect. Dis. 207, 1157–1165 (2013).
Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach (World Health Organization, 2021).
Siedner, M. J. et al. Treated HIV infection and progression of carotid atherosclerosis in rural Uganda: a prospective observational cohort study. J. Am. Heart Assoc. 10, e019994 (2021).
Truong, D. T. et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat. Methods 12, 902–903 (2015).
Franzosa, E. A. et al. Species-level functional profiling of metagenomes and metatranscriptomes. Nat. Methods 15, 962–968 (2018).
Li, D., Liu, C.-M., Luo, R., Sadakane, K. & Lam, T.-W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 31, 1674–1676 (2015).
Hyatt, D. et al. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinform. 11, 119 (2010).
Fu, L., Niu, B., Zhu, Z., Wu, S. & Li, W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 28, 3150–3152 (2012).
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
Li, J. et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32, 834–841 (2014).
Segata, N., Börnigen, D., Morgan, X. C. & Huttenhower, C. PhyloPhlAn is a new method for improved phylogenetic and taxonomic placement of microbes. Nat. Commun. 4, 2304 (2013).
Suzek, B. E. et al. UniRef clusters: a comprehensive and scalable alternative for improving sequence similarity searches. Bioinformatics 31, 926–932 (2015).
Edgar, R. C. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 2460–2461 (2010).
Finn, R. D. et al. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 44, D279–D285 (2016).
Van der Maaten, L. & Hinton, G. Visualizing data using t-SNE. J. Mach. Learn. Res. 9, 2579–2605 (2008).
Caspi, R. et al. The MetaCyc database of metabolic pathways and enzymes. Nucleic Acids Res. 46, D633–D639 (2018).
Nissen, J. N. et al. Improved metagenome binning and assembly using deep variational autoencoders. Nat. Biotechnol. 39, 555–560 (2021).
Parks, D. H., Imelfort, M., Skennerton, C. T., Hugenholtz, P. & Tyson, G. W. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 25, 1043–1055 (2015).
Chaumeil, P.-A., Mussig, A. J., Hugenholtz, P. & Parks, D. H. GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database. Bioinformatics 36, 1925–1927 (2019).
Nayfach, S. et al. CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nat. Biotechnol. 39, 578–585 (2021).
Nayfach, S. et al. Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nat. Microbiol. 6, 960–970 (2021).
Lefkowitz, E. J. et al. Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV). Nucleic Acids Res. 46, D708–D717 (2018).
Russel, J., Pinilla-Redondo, R., Mayo-Muñoz, D., Shah, S. A. & Sørensen, S. J. CRISPRCasTyper: automated identification, annotation, and classification of CRISPR–Cas loci. CRISPR J. 3, 462–469 (2020).
Camargo, A. P. et al. Identification of mobile genetic elements with geNomad. Nat. Biotechnol. 42, 1303–1312 (2024).
Deorowicz, S., Debudaj-Grabysz, A. & Gudyś, A. FAMSA: fast and accurate multiple sequence alignment of huge protein families. Sci. Rep. 6, 33964 (2016).
Capella-Gutiérrez, S., Silla-Martínez, J. M. & Gabaldón, T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972–1973 (2009).
Nwobegahay, J., Selabe, G., Ndjeka, N. O., Manhaeve, C. & Bessong, P. O. Low prevalence of transmitted genetic drug resistance in a cohort of HIV infected naïve patients entering antiretroviral treatment programs at two sites in northern South Africa. J. Med. Virol. 84, 1839–1843 (2012).
Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).
Mavrich, T. N. et al. Characterization and induction of prophages in human gut-associated Bifidobacterium hosts. Sci. Rep. 8, 12772 (2018).