Even small differences between strains of gut bacteria—often within the same species—can sway how these microbes interact with the human body and influence disease outcomes. Now, researchers have found that these differences are linked to where people live and to specific conditions such as inflammatory diseases and body weight. Many of these links came from small groups of microbes rather than entire species. 

The findings, published in Cell, show that health-related patterns in the gut microbiome are more complex than previously thought, highlighting the importance of looking at fine-scale bacterial differences to improve how we study and treat various diseases.

Thanks to advances in DNA sequencing and powerful computer tools, scientists can now study gut microbes in great detail—down to different strains within a single species. However, most research has focused on broad categories of microbes, leaving the variation within species less understood. 

To better understand how strain-level differences between gut bacteria relate to human health, Sergio Andreu-Sánchez at the University of Groningen in the Netherlands and his colleagues analyzed more than 32,000 gut microbiota samples from nearly 25,000 people of all ages in 42 countries.

Geography matters

The team mapped out the genetic relationships among 1,660 bacterial species, which mainly belonged to four groups of bacteria. Gut bacteria can vary depending on where a person lives, with many microbial species showing clear genetic differences across continents, the researchers found. 

For most of the species studied, the farther apart two people lived, the more genetically different their gut microbes were. Some bacteria, such as Eubacterium ventriosum and Ruminococcus torques, showed strong continent-specific patterns. 

However, not all bacteria followed this pattern: species that are passed between people through shared environments or food were less influenced by geography. This suggests that microbes that spread easily can cross geographic boundaries and maintain similar genetics in different places, the researchers say.

Small differences

Next, the team tested whether specific traits—such as age, lifestyle and medication use—are linked to genetic differences within bacterial species in the gut. By analyzing 583 bacterial species and 256 human traits, they found 484 associations. Most of these associations were related to age. For example, Bifidobacterium longum showed distinct genetic groups in infants and adults in both Europe and Africa.

Other links involved conditions such as inflammatory bowel disease and melanoma, as well as factors including pollution and smoking. For example, Collinsella aerofaciens was connected to several diseases in people from different continents. A particular strain of C. aerofaciens was especially common in melanoma and prostate cancer patients, the researchers found. 

“We show that phylogenetic associations are generally related to small microbial clades, rather than larger subspecies entities being associated with a human phenotype or disease,” the authors say. However, they add, larger studies are needed to reliably detect small groups of gut bacteria that may be linked to specific traits or conditions.