Although the gut microbiota is known to influence health and disease, much of its bacterial diversity remains poorly understood because many species are hard to grow in the lab. Now, researchers have found that uncultured gut bacteria, particularly one group called CAG-170, are key contributors to a healthy microbiota. 

The findings, published in Cell Host & Microbe, suggest that CAG-170 and other uncultured gut bacteria can be critical targets for therapeutic development.

Studying gut microbes traditionally relied on lab cultivation, and advances such as DNA-based methods have let scientists study microbes directly from samples, helping reveal new disease-linked bacteria, including a subtype of Fusobacterium nucleatum in colorectal cancer. 

However, much of the bacterial diversity of the gut microbiota remains poorly understood. So, Ana da Silva at the University of Cambridge in the United Kingdom and her colleagues analyzed more than 11,000 gut microbiota samples from diverse populations and diseases to explore the role of bacteria that can’t be cultured in the lab.

Hidden bacteria

The researchers focused on 8,672 samples from healthy people and people with 13 different noncommunicable diseases, mapping the DNA from each sample to a catalog that includes thousands of cultured and uncultured gut bacteria. 

On average, each sample contained about 187 bacterial species, with about 30% being uncultured. These uncultured bacteria were common and more diverse in healthy people than in people with certain conditions such as Crohn’s disease, ulcerative colitis, and obesity. 

Uncultured species were associated with several conditions, despite respresenting only about 12% of microbial abundance. The researchers identified 715 species associated with at least one disease. Crohn’s disease, ulcerative colitis, obesity, and colorectal cancer were largely associated with uncultured species. 

Microbial therapeutics 

Bacterial families such as Oscillospiraceae and Ruminococcaceae were overrepresented in healthy people, whereas Streptococcaceae and Enterobacteriaceae were more common in people with disease. 

A largely uncultured group of bacteria in the human gut microbiota, CAG-170, appeared particularly relevant, as its abundance and genetic diversity correlated with gut health. CAG-170 interacts with other bacterial species, including some linked to disease, the researchers found. 

The results suggest that uncultured gut bacteria, particularly CAG-170, are key players in a healthy gut, the authors say. “This [work] will not only improve our understanding of the role of the microbiome in health and disease but may also inform the development of next-generation microbial therapeutics that leverage the full diversity of the gut ecosystem,” they say.