CAG-170 Gut Bacteria Linked to Better Health

Your gut contains billions of bacteria, not merely a handful. They help digest food, produce useful chemicals and keep the digestive system balanced.

When this community is disrupted, digestive problems can follow. In some cases, it is also associated with more serious, long-term health conditions.

A huge international analysis has now highlighted one particular bacterial group that repeatedly appears in healthier gut microbiomes.

Known as CAG-170, this group has an unusual feature: most of its members have never been cultivated in a laboratory. Scientists chiefly recognise them through their DNA signatures.

CAG-170 bacteria repeatedly linked with health

For the new research, scientists looked for CAG-170 in gut microbiome samples from more than 11,000 people in 39 countries.

Although the bacteria appeared in many participants, a clear trend emerged. People in good health generally had higher levels than those with conditions including inflammatory bowel disease, obesity and chronic fatigue syndrome.

The researchers also examined samples associated with 13 separate diseases, and the pattern remained consistent. CAG-170 levels frequently fell when illness was present.

This does not demonstrate that the bacteria prevents disease. However, it places CAG-170 among the leading microbes that may help identify what a “healthy” gut looks like.

The bacteria behind the findings

Dr Alexandre Almeida, from the University of Cambridge’s Department of Veterinary Medicine, led the study.

“Our work has revealed that CAG-170 bacteria – part of the ‘hidden microbiome’ – appear to be key players in human health, likely by helping us to digest the main components of our food and keeping the whole microbiome running smoothly,” he said.

“We looked at the gut microbes of thousands of people across 39 countries and 13 different diseases including Crohn’s and obesity. We consistently found that people with these diseases had lower levels of CAG-170 bacteria in their gut.”

Why it escaped scientists for so long

Much gut microbiome research has focused on bacteria that readily grow in laboratory dishes. This is understandable: once a bacterium can be grown, researchers can test it, measure what it consumes and produces, and see how it responds under different conditions.

CAG-170 has not been so cooperative. Most bacteria in this group have not been successfully grown, leaving them largely unseen while microbiome science expanded.

Modern DNA technology has altered that. Rather than culturing every microbe, scientists can sequence genetic material from a stool sample and identify the organisms it contains.

The hidden majority in the gut

The study follows earlier work that assembled a major reference collection of genomes from the human gut: the Unified Human Gastrointestinal Genome catalogue.

That project used metagenomics, which examines the genomes of every gut microbe at once before sorting them into individual species.

It identified more than 4,600 bacterial species, including over 3,000 that had not previously been detected in the gut.

“Our earlier work revealed that around two-thirds of the species in our gut microbiome were previously unknown. No-one knew what they were doing there – and now we’ve found that some of these are a fundamental and underappreciated component of human health,” said Dr Almeida.

What CAG-170 may do

A closer examination of CAG-170 genes offered clues about the group’s role in the gut.

The bacteria seem capable of making high amounts of vitamin B12. They also possess enzymes able to break down a broad range of carbohydrates, sugars and fibres in the gut.

One point is important: the researchers believe this vitamin B12 is more likely to support other bacteria than to benefit the person directly.

That matches existing understanding of microbial communities. Many microbes persist by exchanging nutrients, while certain species function as unobtrusive suppliers that sustain others.

Three lines of supporting evidence

The team used more than one approach. First, it searched for CAG-170’s genetic signature in gut microbiome samples collected from people across 39 countries.

The researchers compared healthy participants with people who had conditions such as Crohn’s, colorectal cancer, Parkinson’s and multiple sclerosis.

Second, they computationally assessed the complete gut microbiome composition of over 6,000 healthy people to identify the species most suited to maintaining a stable gut ecosystem.

Among bacteria that are difficult to cultivate in laboratories, CAG-170 again emerged as the group most consistently associated with health.

Third, the scientists investigated dysbiosis, a state in which the gut microbiome is unbalanced. Reduced CAG-170 levels corresponded with a greater likelihood of this imbalance.

Dysbiosis has been associated with numerous long-term conditions, including irritable bowel syndrome, rheumatoid arthritis, and anxiety and depression.

What this may mean for probiotics

Scientists have long hoped that a better understanding of a healthy microbiome would produce improved, more precisely targeted treatments.

The principle is straightforward: establish what a stable gut community contains, identify what changes in particular diseases, and then seek to support what is missing.

“The probiotic industry hasn’t really kept up with gut microbiome research – people are still using the same probiotic species that were being used decades ago,” said Dr Almeida.

“We’re now discovering new groups of bacteria like CAG-170 with important links to our health, and probiotics aimed at supporting them could have a much greater health benefit.”

There is, however, a limitation. Since most CAG-170 bacteria have not been cultivated in the laboratory, researchers must still find ways to grow and test them. Until then, turning this finding into a probiotic or treatment will remain beyond reach.

Even so, the finding is clear: the gut microbiome contains more important contributors than previously recognised, and some have been concealed in plain sight.

The full study appeared in the journal Cell Host & Microbe.