Effects of hormonal contraceptives on the female genital tract microbiota in South African adolescents

Background Young women in sub-Saharan Africa are disproportionally affected by HIV and often rely on injectable hormonal contraception (HC) to prevent unintended pregnancies. However, HC might affect HIV-1 risk through changes in the female genital tract (FGT) microbiota. We examined the impact of three different HC methods on the adolescent female genital tract microbiota and related cytokine and HIV target cell levels at the cervical mucosa in a randomized, crossover trial. Study design and methods 131 adolescent females aged 15 to 19 from Cape Town were enrolled into a randomized, crossover study. The participants were randomized into three study arms: 1. progestin-only injectable norethisterone enanthate (Net-En), 2. combined oral contraceptive pills (COCPs) or 3. combined contraceptive vaginal ring (CCVR) for 16 weeks. Participants then switched to one of the other HC options for a final four months. Vaginal samples were collected at baseline, crossover and exit. STI testing and Nugent scoring were performed at all study visits. Vaginal microbiota was characterized by 16S rRNA gene amplicon sequencing, cytokine concentrations were measured by Luminex and CD4+ T cells analysed by flow cytometry. Results Using fuzzy clustering, three major female genital tract bacterial community types were identified. Two of these were dominated by Lactobacillus species (L. crispatus and L. iners, respectively) and the third was comprised of a diverse group of anaerobic bacteria associated with bacterial vaginosis (BV). In an intention-to-treat analysis at crossover, participants randomized to COCP had a significantly less diverse vaginal microbiota compared to participants randomized to either Net-En or CCVR. The same was observed in an according to protocol analysis at crossover. Using differential abundance testing and random forest analyses, we found that species associated with BV and risk of HIV were significantly more abundant in, and predictive of, participants on Net-En (e.g. Prevotella, Sneathia and Dialister) or CCVR (e.g. Prevotella, Mycoplasma and Parvimonas) compared to COCP while L. iners was more common in the COCP group. Cytokine concentrations were positively associated with a diverse vaginal community and with specific bacterial taxa associated with BV and increased risk of HIV including species enriched in participants on Net-En and NuvaRing. In contrast, there were no association of the frequencies of CD4+ T cells expressing CCR5+ with the vaginal community or BV status. There was likewise no significant association with BV or diversity with Th17 cell frequency, yet BVassociated bacteria were more abundant in participants with higher frequencies of Th17 cells. Conclusions Our data generated from a randomized study suggests that COCPs use may exert a positive influence on genital health through an increase in lactobacilli and a decrease in BV-associated bacterial taxa with an accompanying decrease in overall bacterial diversity, vaginal pH and cytokine levels. In contrast, the vaginal microbiota of participants on Net-En and NuvaRing have increased levels of bacteria associated with BV and HIV risk and increased cytokine levels. We did not observe any association of the frequencies of CD4+ T cells expressing CCR5 or Th17-like cells with the vaginal community, BV status or HC use

Web3 Decentralized Business Models

This paper presents key characteristics of Web3 and how the traditional business model canvas (BMC) requires updates to support managers in the Web3 industry. The characteristics of Web3 include Dapps, wal- lets, interoperability, tokenization, distributed ownership, decentralized communities, creator economy, and token economy. This study investigates how a business model in Web3 is different from the traditional BMC by Osterwalder and Pigneur (2010) based on a Delphi study with a panel of eight experts from the Web3 industry. The contribution of the research outlines a nascent Web3 business model with nine building blocks, including two new blocks specific to the nascent Web3 business models: value co-creation and value distribution. Furthermore, the model expands on the blocks of community and customer, tokenomics, and incentive and reward structures.This paper presents key characteristics of Web3 and how the traditional business model canvas (BMC) requires update to support managers in the Web3 industry. The characteristics of Web3 include Dapps, wallets, interoperability, tokenization, distributed ownership, decentralized communities, creator economy, and token economy. This study investigates how a business model in Web3 is different from the traditional BMC by Osterwalder and Pigneur (2010) based on a Delphi study with a panel of eight experts from the Web3 industry. The contribution of the research outlines a nascent Web3 business model canvas with seven building blocks, which are complemented by two overarching components specific to the nascent Web3 business models: value co-creation and value distribution. Furthermore, the model expands on the blocks of community and customer, tokenomics, and incentive and reward structures

The developing hypopharyngeal microbiota in early life

BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC(2010) cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. RESULTS: Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual’s core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants’ microbiota are more similar to their own, than to others, over time. CONCLUSIONS: Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0215-9) contains supplementary material, which is available to authorized users

Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents

The interaction between gut bacterial and viral microbiota is thought to be important in human health. While fluctuations in female genital tract (FGT) bacterial microbiota similarly determine sexual health, little is known about the presence, persistence, and function of vaginal bacteriophages. We conducted shotgun metagenome sequencing of cervicovaginal samples from South African adolescents collected longitudinally, who received no antibiotics. We annotated viral reads and circular bacteriophages, identified CRISPR loci and putative prophages, and assessed their diversity, persistence, and associations with bacterial microbiota composition. Siphoviridae was the most prevalent bacteriophage family, followed by Myoviridae, Podoviridae, Herelleviridae, and Inoviridae. Full-length siphoviruses targeting bacterial vaginosis (BV)-associated bacteria were identified, suggesting their presence in vivo. CRISPR loci and prophage-like elements were common, and genomic analysis suggested higher diversity among Gardnerella than Lactobacillus prophages. We found that some prophages were highly persistent within participants, and identical prophages were present in cervicovaginal secretions of multiple participants, suggesting that prophages, and thus bacterial strains, are shared between adolescents. The number of CRISPR loci and prophages were associated with vaginal microbiota stability and absence of BV. Our analysis suggests that (pro)phages are common in the FGT and vaginal bacteria and (pro)phages may interact

Genome sequences of anelloviruses, a genomovirus, microviruses, polyomaviruses, and an unclassified caudovirus identified in vaginal secretions from South African adolescents

Other than for papillomaviruses, there is a paucity of whole-genome sequences for bacteriophages and eukaryote-infecting viruses isolated from the female genital tract. Here, we report the genome sequences of 16 microviruses, 3 anelloviruses, 2 polyomaviruses, 1 genomovirus, and 1 caudovirus that were identified in vaginal secretion samples from adolescents in South Africa

Correction to: Microbial function and genital inflammation in young South African women at high risk of HIV infection

Correction to: Microbiome 8, 165 (2020) https://doi.org/10.1186/s40168-020-00932-