Snapshot of the gut microbial diversity of an urban South African population in relation to diet, lifestyle, health and socioeconomic status

Abstract

The human gut microbiome, comprising symbiotic, pathogenic, and commensal organisms, generally maintains a stable composition in adults but is influenced by diet, lifestyle, and environment. South Africa's (SA) shift toward urbanization, with associated increases in sedentary lifestyles and dietary changes, may profoundly impact health, yet understanding of these effects on SA's gut microbiome remains limited. This study details the aim of a snapshot characterization of the gut microbiome in a population of n = 220 urban professional South Africans recruited from the CSIR campus (Pretoria) and the University of the Witwatersrand (Johannesburg). Utilizing comprehensive demographic, lifestyle and dietary surveys (initial 123 variables refined to 101 informative variables) and a stool collection for microbiome profiling, alongside PacBio 16S long-read sequencing and complementary short-read shotgun metagenomics, this research further aims to reveal significant associations between microbial community structure and host demographics, socioeconomic status (SES), diet, lifestyle, and health-related factors. Analyses demonstrated that microbiome composition significantly varies by age, gender, BMI, and ancestry. Younger adults exhibited higher microbial diversity with enriched beneficial taxa such as Bifidobacterium longum and Roseburia faecis, whereas older adults showed lower diversity coupled with increased susceptibility pathways, including Staphylococcus aureus infections. Gender-specific differences emerged, with males enriched in Prevotella stercorea and phenylpropanoid biosynthesis pathways, and females characterized by Bacteroides dorei and distinct lipid metabolism processes. Ancestry-related microbiome differences correlated with dietary adaptations, including Prevotella dominance in African ancestry groups and Bacteroides enrichment in Asian/Multi-ancestry groups. BMI analysis indicated microbial taxa and metabolic pathways uniquely associated with underweight, normal, overweight, and obese groups, highlighting metabolic flexibility and potential dysbiotic states. Notably, despite substantial inter-individual taxonomic variability and limited species-level core microbiome persistence over time, the functional profile remained remarkably stable (82% of functional pathways), emphasizing metabolic redundancy and resilience within urban South African gut ecosystems. Methodological comparisons between 16S long-read and shotgun sequencing highlighted platform-specific biases, underscoring the importance of integrated multi-omics approaches for accurate functional interpretation. This study contributes to the field by characterizing a novel, understudied South African population, challenging Eurocentric microbiome paradigms, and emphasizing urbanization's dual role as disruptor and adapter of gut microbial communities. It advocates for locally tailored microbiome interventions and highlights microbial signatures linked to modifiable urban stressors such as diet and environmental exposures. Future research should prioritize Page 6 of 253 longitudinal multi-omics studies, causal inference analyses, and subpopulation-specific validations to inform targeted public health strategies in rapidly urbanizing African contex