Short- and long-read metagenomics of South African gut microbiomes reveal a transitional composition and novel taxa

To date, human gut microbiome research in adults has focused on western populations, with an additional minority of studies examining nonwestern populations including agriculturalist or hunter-gatherer societies. Yet, the majority of the world’s population resides along a continuum between these two extremes. South Africa is a country in rapid lifestyle and epidemiologic transition and is therefore a unique setting to explore uncharacterized features of the human gut microbiome. Here, we present the first study evaluating gut microbiome composition in transitional South African populations using both short- and long-read sequencing data, which enables both taxonomic profiling as well as generation of contiguous metagenomic assemblies. In this cross-sectional study, we sequenced and analyzed single stool samples from 168 adult females living either in rural Bushbuckridge municipality (n=117) or urban Soweto (n=51) in South Africa. We find that on the microbial community level, the gut microbiomes of South African individuals are consistent with an intermediate state between those of western and other previously studied African populations. Furthermore, we demonstrate that current reference collections are incomplete for nonwestern microbiomes and as a result, patterns of within-cohort beta diversity are reversed compared to the ground truth of reference-agnostic sequence comparison. To improve reference databases for South African populations, we generated several additional complete and contiguous draft genomes via assembly of short and long reads. We identify previously undescribed taxa, such as novel and species, and report the first complete genome assembled from the gut of a human. Taken together, our results suggest that the transitional lifestyle and epidemiological conditions in South Africa contribute to gut microbiota compositions that are intermediate between western and non-western guts and that additional microbial genomic diversity remains to be described in these populations.