How gut bacteria learn and evolve - and shape your future health

Bacteria fill your body by the trillions, especially in your gut, where they outnumber your human cells. These tiny organisms – part of what’s called your microbiome – aren’t just hanging out.

Gut bacteria help you digest food, make vitamins, and even influence your mood and immune system. But here’s the catch: We still don’t fully understand how this system works.

Why do certain bacteria stick around while others don’t? What makes some people’s gut microbes more helpful than others? And could we use that knowledge to prevent or treat disease?

A research team at the California NanoSystems Institute at UCLA has just unlocked a new clue.

Bacteria use DGRs to survive

It turns out that your gut microbes have a special trick up their sleeve. Some bacteria carry bits of genetic machinery called diversity-generating retroelements, or DGRs. These act like mini mutation machines.

DGRs change certain genes, over and over, allowing microbes to adapt to new conditions faster than they could through regular evolution.

DGRs aren’t new to science, but this is the first time anyone has looked at what they’re doing in the gut.

The researchers focused on bacteria commonly found in healthy human intestines. Around one-quarter of the DGRs they studied targeted genes that help bacteria latch onto new surfaces – a key part of forming colonies. These genes control structures called pili, tiny hairlike projections that work like Velcro to help bacteria stick.

In the gut bacteria, the DGRs kept tweaking the genes for pili-binding proteins. By doing this, the microbes were likely increasing their chances of survival in different guts or new environments.

Horizontal gene transfer

Here’s where it gets even more interesting: DGRs don’t just help bacteria adapt. They also spread.

The scientists found that DGRs can hop from one strain of bacteria to another using a method called horizontal gene transfer. And in studies of mothers and their babies, they discovered that infants inherit certain DGRs from their mothers during the first year of life.

This matters because the early microbiome — the bacterial community that forms in the gut during infancy — plays a major role in shaping the immune system.

“The developing microbiome is connected to our developing immune system, and that primes us for the rest of our lives,” said Ben Macadangdang, assistant professor of pediatrics at UCLA.

“When the microbiome is disrupted, we see higher rates of chronic disease later in life. This presents a strong opportunity to engineer the infant gut microbiome to prevent these risks.”

How gut bacteria colonize us

Scientists already know that a messed-up microbiome is linked to a long list of health problems: inflammatory bowel disease, Crohn’s, colon cancer, metabolic syndrome, even conditions like anxiety, depression and autism.

In children, a spike in harmful gut bacteria early on is tied to a higher risk of autoimmune illness down the line.

This study adds another piece to the puzzle. It shows that DGRs are a key part of how gut bacteria evolve, stick around, and shape our biology – from infancy through adulthood.

The DGR system was first discovered in Jeff F. Miller’s lab, who is director of CNSI and a professor of microbiology at UCLA. He explained just how powerful these elements are.

“One of the real mysteries in the microbiome is exactly how bacteria colonize us,” said Miller. “It’s a highly dynamic system intimately connected with human physiology, and this knowledge about DGRs could one day be applied for engineering beneficial microbiomes that promote good health.”

Miller also pointed out how efficient DGRs are compared to similar systems in the human body. Our immune cells can produce a huge variety of antibodies, but they do it once per cell. DGRs, on the other hand, can create mutations again and again in the same cell – producing far more variety.

To put this in perspective, if each unique antibody in your immune system were a grain of sand, it would take less than a quarter of 1% of the Empire State Building to hold them all. For DGRs? You’d need the equivalent of 270 million Empire State Buildings.

The future of human gut science

In their study, the researchers examined gut bacteria from a group called Bacteroides, a common resident of the human gut. They found more than 1,100 different DGRs. On average, each bacterial strain carried at least one. Some had up to five.

The team focused on the ones affecting pili genes – the same sticky structures that help bacteria cling to surfaces.

The DGRs’ job was to keep remixing the proteins that help these pili do their job. That flexibility is likely why these bacteria are so successful in so many different people.

“We think DGRs allow the bacteria to rapidly change what their pili can adhere to,” said Macadangdang. “A bacterium may be optimized for one person’s gut, but if it goes out and tries to colonize someone else, it encounters a very different environment.”

“Finding something new to bind to gives the bacteria an advantage, and we think that’s why we see so many DGRs within the microbiome.”

Gut bacteria: The new health frontier

The research team is just getting started. They plan to keep exploring how DGRs work and what they might do in both healthy and unhealthy guts.

The hope is that this knowledge could lead to new ways to engineer the microbiome – possibly using DGRs themselves – to treat disease, improve immunity, or even customize gut bacteria for better health outcomes.

“We’re at this really early stage,” Miller said. “There are so many questions that this raises, we’re just realizing how much we don’t know about DGRs in the microbiome, or what exploiting them for applications could yield. I’ve never been more excited about what’s going to come next.”

The full study was published in the journal Science.

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