Studies of human microbiome have ignored the developing world, potentially compromising treatments | Science

Thousands of studies have linked the trillions of microbes living in and on our bodies to conditions from cancer to autism to depression. But most microbiome samples come from wealthy countries in North America and Europe, a new analysis finds, distorting our understanding of human-microbe interactions.

“There are many ethnic groups and geographical locations that are dramatically underrepresented,” says Rob Knight, a microbiologist at the University of California, San Diego, who was not part of the study. The distribution of samples “speaks to deep inequities in how research is funded and conducted.” A fuller picture of how different microbiomes impact health could aid the development of diagnostics and therapies for specific populations, says Knight, who is working to make microbiome sampling more equitable.

Unlike the human genome, which only varies slightly among individuals, the human microbiome differs radically. Diet, exercise, socioeconomic status, antibiotic use, and even pollution can influence its makeup, with some studies suggesting geography is one of the strongest variables.

Research comparing the gut microbiomes of people from the Amazonas state in rural Venezuela, rural Malawi, and U.S. metropolitan areas shows microbiomes in less industrialized environments are more diverse. Studies have also found that compared with microbiomes in urban populations, those of hunter-gatherers in Tanzania are very dynamic, changing with the seasonal availability of foods.

To see how well microbiome research captures these global variations, Ran Blekhman, Elizabeth Adamowicz, and Richard Abdill of the University of Minnesota, Twin Cities, compiled geographic information for more than 440,000 publicly available microbial DNA sequences from the past 11 years. They found more than 40% of the samples were from the United States—almost five times as many as from any other country, the scientists report today in PLOS Biology.

The researchers then compared the number of samples with each region’s population. They found Europe and North America provided more than 71% of samples even though they hold about 15% of the world’s population, whereas central and southern Asia contributed 1.5% of samples from almost 26% of the world’s population. “It is clear that our understanding of the ‘human’ microbiome does not include most humans,” Abdill says. “Our study is a step towards quantifying this disparity.”

Clement Adebamowo, an epidemiologist at the University of Maryland, Baltimore, agrees. “[The authors] have done a great service to the field by highlighting the scope of the problem,” he says.

Missing microbes

To understand how microbes that live on and in us affect health, researchers sequence their DNA. But most of the world’s people are underrepresented in the data.

graph showing variations in sequenced DNA in different regions of the world
(GRAPHIC) C. BICKEL/SCIENCE; (DATA) U.S. National Library of Medicine/National Center for Biotechnology Information; U.N. Department of Economic and Social Affairs/Population Division (2019), World Population Prospects 2019, Online Edition. Rev. 1; R.J. Abdill, E.M. Adamowicz; R. Blekhman/University of Minnesota

The sparse representation of developing countries reflects low levels of research funding, lack of state-of-the-art technology, and few people trained to analyze samples, says Adebamowo, who has a joint appointment at the Institute of Human Virology, Nigeria. Countries may also focus research efforts on more urgent needs, such as malaria, he says.

The cost of equipment to identify bacteria is a major barrier. “[We] have a very difficult time having access to those technologies,” says Pablo Jarrín Valladares, a biologist at the National Institute of Biodiversity in Quito, Ecuador, who leads the Ecuadorian Microbiome Project. Bureaucracy can also delay the permits required for sampling. “The issue for us in catching up is reducing the bumps.”

A lack of specialists to analyze data is another obstacle in developing countries, says Victor Pylro, a molecular microbial ecologist at the Federal University of Lavras and coordinator of the Brazilian Microbiome Project. He, Jarrín Valladares, and other researchers hope to attract funding from the private sector and foreign institutions by forming local networks. With funding from Thermo Fisher Scientific, Pylro’s team is already working to evaluate how the microbiome changes when people have COVID-19.

Blekhman, Knight, and others point to the Human Heredity and Health in Africa (H3Africa) consortium, which has boosted genomic science in the region, as an example of local groups improving sampling and data sharing. Adebamowo, who leads H3Africa’s African Collaborative Center for Microbiome and Genomics Research (ACCME), says the consortium has helped African researchers build infrastructure and expertise, and is now taking on microbial diversity in health and disease. At ACCME, Adebamowo and colleagues are working to find biomarkers linking variations in the vaginal microbiome with persistent high-risk human papillomavirus infections in African women.

For María Gloria Domínguez Bello, a microbiome researcher at Rutgers University, New Brunswick, having samples from populations across the world is essential to understanding not just disease, but also human history and diversity. “Our microbiomes are coevolved entities,” she says. “These are genomes that belong to us in the sense that we can’t live without them, and they can’t live without us.” She, Knight, and others have launched a Microbiota Vault in Basel, Switzerland, a storage project akin to the “doomsday” crop seed vault, aiming to preserve microbiome samples from all over the world.

“With the way the field is growing, the best time to course correct was 5 years ago,” Abdill says. “But the second best time is now.”