Table 2 Summary of the African Human Urogenital Microbiome studies characteristics
Sample origin (country) | Disease of focus | Sample type | Methods and platform | Scientists involved (affiliation) | Funding source for the study | Study type | Number of participants | Conclusion | Reference |
|---|---|---|---|---|---|---|---|---|---|
Urogenital | |||||||||
Burkina Faso | HIV | Cervicovaginal lavage | 16S rRNA, 454 pyrosequencing | Burkina Faso, France, UK, USA | NIH, Agence Nationale de Recherche sur le Sida, the Veterans Affairs Research Service, the Mucosal and Vaccine Research Program Colorado | Nested case-cohort study | 64 | The data suggests that alterations in vaginal microbial communities are associated with an increased risk for perinatal MTCT. | [135] |
Kenya | Genital ulcer disease | Genital ulcer specimens | 16S rRNA, V1-V2 region, 454 pyrosequencing | Canada, USA | Chicago Development Center for AIDS Research | Cross-sectional | 59 | Anaerobic bacteria are more common in genital ulcers of uncircumcised men. | [136] |
Kenya | HIV-1 | Vaginal swabs | 16S rRNA, V1-V3 region, 454 pyrosequencing | Kenya, USA | Bill and Melinda Gates Foundation Grand Challenges Explorations, NIH, the Gilead Foundation grant | Longitudinal | 72 | Group counseling is effective in reducing intravaginal practices, and this in turn improved the vaginal health. | [137] |
Kenya | None | Cervicovaginal lavage | 16S rRNA, V3 region, Illumina MiSeq | Canada, Kenya | CIHR, Grand Challenges Canada, The Ontario HIV Treatment Network | Cross-sectional | 67 | High-risk sexual behavior is associated with greater diversity of the vaginal microbiota and lack of Lactobacillus species. | [138] |
Kenya | HIV | Vaginal swabs | 16S rRNA, V3 region, Illumina MiSeq | Canada, Kenya | Canadian Institutes of Health Research (CIHR) | Cohort | 58 | MPA-induced hypoestrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli and allow for greater bacterial diversity in the vaginal microbiota. | [139] |
Kenya | Trichomonas vaginalis or Chlamydia trachomatis infections in pregnancy | Vaginal swabs | 16S rRNA, V2 V4 V8 regions, Ion Torrent PGM | Belgium, Kenya, UK | Not specified | Case-control | 53 | The vaginal microbiomes of TV and CT-infected women were markedly different from each other and from women without TV and CT. Future studies should determine whether the altered microbiomes are merely markers of disease, or whether they actively contribute to the pathology of the two genital infections. | [140] |
Kenya, Tanzania, Uganda | HIV | Vaginal swabs | 16S rRNA, V3–V4 regions, 454 pyrosequencing | Kenya, USA | NIH | Nested case-control | 110 | Vaginal microbiota could influence women’s risk of HIV acquisition at multiple levels. | [141] |
Kenya | HIV | Semen | 16S rRNA, V3–V4 regions, 454 pyrosequencing | Kenya, UK, USA | NIH, the University of Washington Center for AIDS Research, the KEMRI-Wellcome Trust Research Programme at the Centre for Geographic Medicine Research-Kilifi | Cross-sectional | 13 | Most of these HIV-1-infected men had bacteria in their semen. Antiretroviral therapy use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. | [142] |
Kenya | Bacterial vaginosis | Cervicovaginal lavage | 16S rRNA, V3–V4 regions, Illumina HiSeq | Canada, Kenya, USA | Canadian Institutes of Health Research, Ontario HIV Treatment Network, NIH | Observational prospective cohort design | 45 | Bacterial Vaginosis treatment reduced genital CD4+ T-cell HIV susceptibility and IL-1 levels, but dramatically increased the genital chemokines that may enhance HIV susceptibility; the latter effect was related to the restoration of a Lactobacillus inner–dominated microbiota. Further studies are needed before treatment of asymptomatic Bacterial Vaginosis can be recommended for HIV prevention in women from African, Caribbean, and other Black (ACB) communities. | [143] |
Nigeria | High-risk human papillomavirus infection | Mid-vaginal swabs | 16S rRNA, V4 region, Illumina MiSeq | Nigeria, UK, USA | NIH | Cross-sectional | 278 | Vaginal microbial composition in African women is similar to that of African American women. Also, hrHPV infection was strongly associated with the abundance of various vaginal bacterial taxa. | [144] |
Nigeria | High-risk human papillomavirus infection | Mid-vaginal swabs | 16S rRNA, V3–V4 regions, Illumina MiSeq | Nigeria, USA | NIH | Longitudinal | 194 | A significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but reverse causation could not rule out. | [145] |
Nigeria | Schistosomiasis infection and bladder pathology | Urine | 16S rRNA, V3 region, Ion Torrent PGM | India, Nigeria, USA | NA | Cross-sectional | 70 | The urinary microbiome is a factor to be considered in developing biomarkers, diagnostic tools, and new treatment for urogenital schistosomiasis and induced bladder pathologies. | [146] |
Rwanda | Bacterial vaginosis | Vaginal swabs | 16S rRNA, V3–V4 regions, Illumina HiSeq | The Netherlands, Rwanda, UK | DFID/MRC/Welcome Trust Joint Global Health Trials Scheme as a Development Project, University of Liverpool | Prospective cohort | 68 | Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments. | [147] |
Rwanda, USA | HIV | Cervicovaginal lavage | 16S rRNA, 454 multitag pyrosequencing | Rwanda, USA | NIH, the Chicago Developmental Center for AIDS Research | Case-control | 40 | Similar prevalence of most major bacterial genera and Lactobacillus species in Rwanda and USA women. | [148] |
Rwanda | Bacterial vaginosis | Vaginal swabs | 16S rRNA, V6 region, Illumina MiSeq | Canada, Rwanda | Canadian International Development Agency, CIHR | Cross-sectional | 131 | Differences in the vaginal metabolome are driven by bacterial diversity. | [31] |
Rwanda | None | Vaginal swabs | 16S rRNA, V6 region, Illumina MiSeq | Canada, Rwanda, USA | Canadian Institute Health Research Vogue Team Grant | Randomized, blinded, placebo-controlled clinical trial | 13 | Overall women were receptive to the probiotic concept, but the lack of information on such products and logistical and economical challenges pose problems for wider population engagement. | [149] |
South Africa | HIV, Papillomavirus infection and cervical cancer | Vaginal swabs | 16S rRNA, V3–V4 regions, Illumina HiSeq | France, The Netherlands, South Africa, UK | The European Commission 7th Framework Programme, University of Liverpool | Nested case-control | 448 | hrHPV infection (and/or increased sexual risk-taking) may cause anaerobic vaginal dysbiosis, but a bidirectional relationship is also possible. In this population, dysbiosis did not increase CIN2þ risk, but CIN2þ increased dysbiosis risk. The CIN2þ risk associated with progestin-only injectable use requires further evaluation. | [147] |
South Africa | Papillomavirus infection | Cervical swabs | 16S rRNA, V3–V4 regions, Illumina MiSeq | South Africa | National Research Foundation of South Africa, Poliomyelitis Research Foundation (PRF), Cancer Association of South Africa (CANSA), University of Cape Town (UCT) Research Incentive Scheme, UCT Cancer Research Initiative | Cross-sectional | 87 | A majority of the reproductive-age HIV-seronegative Black South African women (57%) had cervical microbiota not dominated by Lactobacillus, the bacteria assumed to constitute a healthy cervical microbiota. These cervical microbiota were associated with findings suggestive of bacterial vaginosis. | [150] |
South Africa | None | Cervical swabs | 16S rRNA, V4 region, Ion Torrent PGM | South Africa | National Research Foundation (NRF) of South Africa, Poliomyelitis Research Foundation (PRF), Cancer Association of South Africa (CANSA), University of Cape Town (UCT) Research Incentive Scheme, UCT Cancer Research Initiative | Retrospective cross-sectional | 62 | To date, this remains the first study to examine the association between prevalent HPV and cervical microbiota in a Black South African cohort. Further investigations into the role of the cervical and vaginal microbiome in HPV/HR-HPV infections are warranted. | [151] |
South Africa, Australia, China | Prostate cancer | Prostate tumor samples | Shotgun metagenomics, Illumina HiSeq | Australia, Canada, China, South Africa | Cancer Association of South Africa, China Scholarship Council, University of Sydney Foundation, Australian Prostate Cancer Research Centre, New South Wales | Cross-sectional | 6 | Our study provides suggestive evidence for the presence of a core, bacteria‐rich, prostate microbiome. While unable to exclude fecal contamination, the observed increased bacterial content and richness within the African vs non-African samples, together with elevated tumor mutational burden, suggests the possibility that bacterially driven oncogenic transformation within the prostate microenvironment may be contributing to aggressive disease presentation in Africa. | [152] |
South Africa | Chlamydia trachomatis infection | Vulvo-vaginal, vaginal lateral wall, and endocervical swabs | 16S rRNA, V4 region, Illumina MiSeq | Australia, South Africa, USA | European and Developing Countries Clinical Trials Partnership (EDCTP) Strategic Primer grant, South African Department of Science and Technology | Cohort | 72 | In this African adolescent cohort, significant differences between the lateral vaginal wall and endocervical microbiota diversity and composition were evident, although neither were strongly associated with Chlamydia trachomatis infection. | [153] |
South Africa | None | Cervical swabs | 16S rRNA, V4 region and Shotgun metagenomic sequencing, Illumina MiSeq | South Africa, USA | Bill and Melinda Gates Foundation, IAVI, NIH | Prospective cohort | 146 | The bacterial microbiome plays a role in modulating HIV risk, genital microbiome can significantly alter host inflammation. | [154] |
South Africa | Bacterial vaginosis and sexually transmitted infections | Vulvo-vaginal swabs | 16S rRNA, V4 region, Illumina MiSeq | South Africa, USA | European and Developing Countries Clinical Trials Partnership, the South African Department of Science and Technology | Cross-sectional | 102 | Young 16–22-year-old women in under-resourced Cape Town community have a high incidence of STIs, particularly chlamydia and high-risk HPV, as well as Bacterial vaginosis. The high abundance of Prevotella amnii may increase HIV risk, given its inflammatory capacity. Laboratory-based testing for STIs (chlamydia and gonorrhea in particular) appear to be warranted in this community, together with further monitoring or treatment of BV. | [23] |
South Africa | Bacterial vaginosis | Vulvo-vaginal swabs | 16S rRNA, V4 region, Illumina MiSeq | Australia, South Africa, USA | European and Developing Countries Clinical Trials Partnership (EDCTP), South African Department of Science and Technology | Cohort | 168 | We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection. | [24] |
South Africa | Bacterial vaginosis | Vaginal swabs | 16S rRNA, V4 region, Illumina MiSeq | Australia, South Africa, USA | European and Developing Countries Clinical Trials Partnership (EDCTP) Strategic Primer grant, South African Department of Science and Technology | Cohort | 181 | Our results therefore suggest that HIV prophylactic approaches targeting the vaginal microbiota should be geographically tailored. | [25] |
South Africa | HIV | Cervicovaginal lavage | 16S rRNA, V3–V4 regions, Illumina MiSeq | Canada, South Africa, Sweden, USA | CIHR, the Department of Pharmaceutics at the University of Washington, the Public Health Agency of Canada | Clinical trial | 688 | This study provides evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism. | [155] |
South Africa | HIV | Cervical swabs | 16S rRNA, V4 region, Illumina MiSeq | South Africa, USA | Bill and Melinda Gates Foundation, IAVI, NIH, the Harvard Center for AIDS Research | Prospective study | 236 | The results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings may be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa. | [156] |
Tanzania | Cervical cancer and HIV | Cervical swabs | 16S rRNA, V4 region, Illumina MiSeq | Tanzania, USA | NA | Cross-sectional | 144 | These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought. | [157] |
Tanzania | HIV | Vaginal swabs | 16S rRNA, V6 region, Illumina | Canada, Tanzania, The Netherlands | Natural Sciences and Engineering Research Council of Canada | Longitudinal | 132 | The vaginal microbiota among women living with HIV in Sub-Saharan Africa constitutes several profiles associated with a normal microbiota or BV. | [30] |
Uganda | HIV | Coronal sulcus swabs | 16S rRNA, V3–V6 regions, 454 pyrosequencing | Uganda, USA | NIH | Randomized control trial | 156 | Combining bacterial quantification with parallel sequencing showed that circumcision resulted in significant decreases in the absolute abundances of several anaerobic bacterial taxa that defined the uncircumcised penis microbiome. | [26] |
Uganda | HIV | Coronal sulcus swabs | 16S rRNA, V3–V6 regions, 454 pyrosequencing | Canada, Uganda, USA | NIH, Bill and Melinda Gates Foundation, the Doris Duke Charitable Foundation | Cross-sectional | 165 | Female partner Nugent bacterial vaginosis is significantly associated with penile microbiota. The data support the exchange of bacterial vaginosis-associated bacteria through intercourse, which may explain BV recurrence and persistence. | [27] |
Uganda | Genital anaerobic bacterial overgrowth | Subpreputial swabs | 16S rRNA, V3–V6 regions, 454 pyrosequencing | Uganda, USA | NIH | Case-control | 147 | The PrePex-associated increase in anaerobes may account for unpleasant odor and a possible heightened risk of tetanus. | [28] |
Uganda | HIV | Coronal sulcus swabs | 16S rRNA, V3–V4 regions, Illumina MiSeq | Canada, Uganda, USA | NIH, Bill and Melinda Gates Foundation, CIHR | Case-control | 182 | Penile anaerobes may be a sexually transmissible risk factor for HIV and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women. | [29] |
Uganda | None | Coronal sulcus swabs | 16S rRNA, V3–V4 regions, 454 pyrosequencing | Uganda, USA | NIH, Translational Genomics Research Institute | Randomized control trial | 12 | The reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases. | [158] |
Uganda | HIV | Vaginal swabs | 16S rRNA, V3–V4 regions | Canada, Uganda, USA | NIH | Double-blind randomized placebo-controlled trial | 92 | The vaginal microbiome of HIV-infected women was not affected by the initiation of ART or immune reconstitution in this observational study. Further research is needed to explore the long-term effects of ART treatment on the vaginal microbiome. | [159] |
Zambia | HIV | Vaginal swabs | Shotgun metagenomics, Illumina HiSeq | USA, Zambia | Global Alliance to Prevent Prematurity and Stillbirth and the Center for AIDS Research, NIH | Cohort | 256 | Pregnant women in Zambia, particularly those with HIV, had diverse anaerobe-dominant vaginal microbiota. | [160] |
Zimbabwe | HIV | Vaginal swabs | 16S rRNA, V4 region, Illumina MiSeq | South Africa, USA, Zimbabwe | Letten Foundation Norway | Cross-sectional | 356 | Pregnant women living with HIV have more diverse vaginal communities and altered community structure compared to pregnant uninfected women. However, preterm birth was associated with HIV infections independent of vaginal community state type. | [161] |