January 29th, 2025 – by Rebecca Handler

The human gut is a microbial universe that holds immense sway over our health. These tiny organisms influence digestion, immunity, and even diseases like diabetes and cardiovascular conditions. However, most research has focused on populations in industrialized countries, leaving out the 84% of people who live in low- and middle- income countries. This means we’ve been working with a skewed picture of the microbiome – until now.

The groundbreaking AWI-Gen 2 Microbiome Project is changing this by focusing on African populations, uncovering insights that could reshape how we understand health on a global scale.

Inside AWI-Gen 2: Charting New Territory in Microbiome Research

This ambitious study, jointly led by Ami S. Bhatt, MD, PhD, Scott Hazelhurst, PhD and their respective teams in Stanford’s Department of Medicine and the University of the Witwatersrand, is the largest population-representative study of its kind. It mapped the gut microbiomes of 1,801 women and 19 men across six diverse communities in Burkina Faso, Ghana, Kenya, and South Africa. It didn’t just skim the surface – researchers used advanced sequencing to dive deep into the microbiota, uncovering unique bacteria and viruses while linking their presence to geography, lifestyle, and health conditions. Unlike many microbiome studies that focus almost exclusively on high-income populations, this project intentionally centered on diverse African communities, from rural farming villages to bustling urban settlements.

The AWI-Gen 2 project revealed not only the incredible diversity of the human gut but also how it changes with urbanization, diet, and environmental factors. For example, the bacterium Treponema succinifaciens, often associated with traditional diets, was thought to be completely absent in urban environments. Yet researchers found it thriving in some African cities, possibly due to lower antibiotic use and dietary habits retained from rural areas. “It was interesting to see that some organisms that were previously believed to be ‘lost’ in modern, non-hunter-gatherer populations are still present in some of the people we studied,” Bhatt noted.

Additionally, the study revealed that individuals living in dense, underdeveloped urban areas – informal settlements – had microbiomes reflecting both urban and rural features. “This suggests that population density isn’t the best way to differentiate lifestyles,” Bhatt explained. “Instead, factors like access to cheap, highly processed foods or exposure to livestock and sources of drinking water may play a bigger role.”

The Gut-HIV Connection

Another striking discovery ties the gut microbiome to HIV, a disease that remains a significant health challenge in South Africa and Kenya. The study identified specific bacterial species linked to HIV infection that had not been previously associated with the disease, including Dysosmobacter welbionis and Enterocloster sp.. These findings could open new doors for understanding how HIV affects the immune system and how gut health might play a role in managing the disease.

Beyond its medical implications, the project uncovered 1,005 new bacterial genomes and an astonishing 40,135 previously unknown viral genomes, highlighting just how much microbial diversity has gone unnoticed in underrepresented populations. This research isn’t just about filling in gaps – it’s about expanding the boundaries of what we know about human health.

Ethical and Inclusive Science That Powers Next-Gen Research 

The project’s focus on involving a broad range of local scientists and working directly with some of the community members they studied sets it apart in another critical way: it was designed to empower local communities. By partnering with African researchers and ensuring community involvement at every step, AWI-Gen 2 offers a model for ethical and equitable global health research. “This study involved a strong, equitable research partnership between scientists on two continents,” Bhatt emphasized. “In addition to this, we engaged local communities in everything from study design to reporting research results back. By not taking a ‘one size fits all’ approach to microbiome research, we have identified many patterns of microbiome composition that will help refine and better design and match potential microbiome-based interventions.”

A key element of this inclusivity was the mentoring and active involvement of early-career researchers from both continents. “Trainees from both research sites – Ovokeraye Oduaran and Luicer Olubayo from Africa; Dylan Maghini, Jakob Wirbel, and Jane Cook from the USA – were heavily engaged in all aspects of the research. It’s not just about doing great research; it’s about developing future global research leaders.”

A More Inclusive Atlas for the Future

The findings from AWI-Gen 2 could lead to targeted health interventions that are more relevant and effective for populations that have been historically underserved by microbiome research. It also challenges scientists to think more globally, recognizing that discoveries in one part of the world can unlock solutions for everyone.

By spotlighting underrepresented populations, the AWI-Gen 2 Microbiome Project is transforming the gut microbiome atlas into a more inclusive and globally relevant tool. It’s a reminder that science thrives when everyone’s story gets told – and that sometimes, the smallest organisms hold the biggest keys to better health.