Human gut microbiome research focuses on populations living in high-income countries and to a lesser extent, non-urban agriculturalist and hunter-gatherer societies. The scarcity of research between these extremes limits our understanding of how the gut microbiota relates to health and disease in the majority of the world’s population. Here, we evaluate gut microbiome composition in transitioning South African populations using short- and long-read sequencing. We analyze stool from adult females living in rural Bushbuckridge (n = 118) or urban Soweto (n = 51) and find that these microbiomes are taxonomically intermediate between those of individuals living in high-income countries and traditional communities. We demonstrate that reference collections are incomplete for characterizing microbiomes of individuals living outside high-income countries, yielding artificially low beta diversity measurements, and generate complete genomes of undescribed taxa, including Treponema, Lentisphaerae, and Succinatimonas. Our results suggest that the gut microbiome of South Africans does not conform to a simple “western-nonwestern” axis and contains undescribed microbial diversity.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes-derived from activity scores-were examined across multiple sub-Saharan African populations based on bioinformatics analysis of 961 high-depth whole genome sequences. This was followed by characterization of novel star alleles and suballeles in a subset of the participants via targeted high-fidelity Single-Molecule Real-Time resequencing (Pacific Biosciences). This study revealed varying frequencies of known CYP2D6 alleles and predicted phenotypes across different African ethnolinguistic groups. Twenty-seven novel CYP2D6 star alleles were predicted computationally and two of them were further validated. This study highlights the importance of studying variation in key pharmacogenes such as CYP2D6 in the African context to better understand population-specific allele frequencies. This will aid in the development of better genotyping panels and star allele detection approaches with a view toward supporting effective implementation of precision medicine strategies in Africa and across the African diaspora.

Key Points Question Are novel cardiovascular disease (CVD) risk factors, such as carotid atherosclerosis (carotid intima-media thickness) and microalbuminuria, associated with with 10-year atherosclerotic CVD (ASCVD) risk in sub-Saharan African adults free of established CVD? Findings In this cross-sectional study of 9010 adult participants, microalbuminuria measured using spot urine albuminuria was associated with both carotid atherosclerosis and a high 10-year risk of ASCVD. Meaning These findings suggest that spot urine albuminuria can be used in rural and urban sub-Saharan African settings to screen for individuals with a higher risk of ASCVD; however, clinical events data may be needed to confirm these findings.

Background Half of global child deaths occur in sub-Saharan Africa. Understanding child mortality patterns and risk factors will help inform interventions to reduce this heavy toll. The Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso was described previously, but patterns and potential drivers of heterogeneity in child mortality in the district had not been studied. Similar studies in other districts indicated proximity to health facilities as a risk factor, usually without distinction between facility types. Methods Using Nanoro HDSS data from 2009 to 2013, we estimated the association between under-5 mortality and proximity to inpatient and outpatient health facilities, seasonality of death, age group, and standard demographic risk factors. Results Living in homes 40–60 min and > 60 min travel time from an inpatient facility was associated with 1.52 (95% CI: 1.13–2.06) and 1.74 (95% CI: 1.27–2.40) greater hazard of under-5 mortality, respectively, than living in homes < 20 min from an inpatient facility. No such association was found for outpatient facilities. The wet season (July–November) was associated with 1.28 (95% CI: 1.07, 1.53) higher under-5 mortality than the dry season (December–June), likely reflecting the malaria season. Conclusions Our results emphasize the importance of geographical proximity to health care, distinguish between inpatient and outpatient facilities, and also show a seasonal effect, probably driven by malaria.