Towards equitable research: Expanding the human gut microbiome atlas of Africa

Led by molecular bioscientists from the University of the Witwatersrand, South Africa, the AWI-Gen 2 Microbiome Project collected extensive clinical and demographic data from 1,801 women in Burkina Faso, Ghana, Kenya and South Africa. The goal: to understand how geography, lifestyle, genetics and the environment shape the gut microbiome.

“Altogether, this study demonstrates the importance of investigating the gut microbiome in undersampled populations, provides a framework for equitable microbiome research and represents the largest population-representative profile of African gut microbiomes so far,” the researchers wrote recently in the journal Nature.

The work was supported by the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health & Human Development, the Office of the Director of the National Institutes of Health (NIH), the South African Department of Science and Innovation, and the Stanford Center for Innovation in Global Health.

The importance of geographic diversity

AWI-Gen 2 is a follow-up study to a first phase conducted from 2012 to 2017 through pilot microbiome projects at two South African sites to examine the human microbiome and its contribution to disease. This second phase (2018-2023) incorporates six research centers in four countries.

“Here, 17 years later, the AWI-Gen 2 Microbiome Project is a landmark collaborative research effort that extends these goals to diverse LMIC populations in Africa: rural and predominantly horticultural areas (Nanoro, Burkina Faso and Navrongo, Ghana), rapidly transitioning rural areas (Agincourt and DIMAMO, South Africa), urban industrial informal settlements (Viwandani and Korogocho settlements in Nairobi, Kenya) and an urban post-industrial settlement (Soweto, South Africa),” the researchers wrote.

The study focused on non-pregnant women ages 32 to 98 who had lived in their communities for at least 10 years. The cohort also aligns with a companion menopause study.

With support from trained field workers, participants completed surveys and provided blood, urine and stool samples. DNA was extracted from each stool sample, and all individuals were genotyped using the H3Africa Custom SNP Array—a research tool designed to improve genetic research in African populations.

The study reported that geography had the strongest influence on gut microbiome diversity and the presence of certain microbial species. Differences in urbanization level such as access to clean water, healthcare, diet and disease exposure played a major role.

The researchers contrasted their resource-intensive, cross-sectional sampling with studies typically focused on high-income populations, whose results “often do not translate to populations with different lifestyle practices, health challenges and access to healthcare, and varied environmental exposures.” They also noted that microbiome studies often rely on facility-based convenience-sampling models, which are generally not representative of a broader population.

What the metagenomes say

By analyzing the complete DNA content of complex microbial communities in stool samples known as metagenomes, AWI-Gen 2 reported microbiome variations that correlated with gradients in population density and access to resources.

“Using shotgun metagenomic sequencing, we identify taxa with geographic and lifestyle associations, including Treponema and Cryptobacteroides species loss and Bifidobacterium species gain in urban populations,” the researchers wrote. “We uncover 1,005 bacterial metagenome-assembled genomes, and we identify antibiotic susceptibility as a factor that might drive Treponema succinifaciens absence in urban populations.”

They also discovered over 40,000 previously unknown viral genomes, including nine new and prevalent jumbo phages—viruses with unusually large genomes that infect bacteria and have been investigated as novel approach to treat bacterial infections.

Interestingly, some microbial communities differed between sites with similar subsistence strategies and industrialization levels. For example, Bifidobacterium and Cryptobacteroides were found at similar levels in both Nairobi and Soweto, whereas abundances of Prevotella, Bacteroides and Phocaeicola in Nairobi were more typical of the rural and semi-rural sites.

“Crucially, these findings illustrate that ‘urbanization’ or ‘industrialization’, which are commonly cited variables that impact the microbiome in previous research including our own, cannot adequately capture lifestyle and environmental differences between different urban areas and between different rural areas,” the researchers noted, suggesting that the high in- and out-migration rates and extensive circular migration in Nairobi’s informal settlements could affect microbiome composition.

There was also an HIV infection signature defined by several taxa not previously associated with the virus and inflammation, including Dysosmobacter welbionis and Enterocloster sp. While the study represents one of the largest microbiome studies of women living with HIV to date, it acknowledged that more research is needed to disentangle the effects of HIV infection and other confounding variables on microbiome composition.

“Future studies can leverage these data, along with the foundation for community-engaged and equitable research described herein, to close the gap in global representation in microbiome research,” the researchers concluded. “Moreover, there is every reason to anticipate that the platforms and findings that emerge will enhance disease management, health and well-being among communities living in a diversity of contexts.”

Source: Nature. doi: 10.1038/s41586-024-08485-8. “Expanding the human gut microbiome atlas of Africa”.Authors: Dylan Maghini et al.