Genes play an active role in gut health, researchers find

Keeping the beneficial bacteria in our guts happy and abundant is big business — but researchers at The University of Sydney have now found that genes play an active role in shaping bacterial communities, putting into question the idea that gut health can only be influenced by diet and supplements. Their work has been published in The EMBO Journal.

“After decades of research linking the gut microbiome to almost every chronic disease, it may seem like we’re all being held hostage by the bugs that live inside us,” said first author Dr Stewart Masson, from Sydney’s Charles Perkins Centre.

“While gut microbes certainly influence everything from diabetes to depression, this study has revealed that our bodies aren’t just passive hosts.”

The researchers found that mice with certain genes produced natural peptides — or small proteins — called alpha-defensins, which act as gardeners of the microbiome, shaping which gut bugs thrive and weeding out undesirable bacteria. Alpha-defensin peptides are also found in people, and may be highly relevant to human health.

The researchers were originally studying genetic influences of insulin resistance — a key cause of type 2 diabetes and heart disease — when they noticed that certain mice that were less prone to the condition had genes that changed the production of defensin peptides in cells lining the intestine. Mice whose genes made more alpha-defensins were healthier than mice who made less.

“Defensin peptides are present in a wide range of organisms, from plants to mice and humans, and are thought to be the earliest precursor to an immune system,” Masson said. “Mice and humans seem to have evolved many defensin genes, each making a different peptide. It is thought that this diversity allows our immune system to fend off a wide range of attackers”.

To test their findings, the researchers synthesised the defensin peptides in the lab and fed them to mice without the genes. The experiments showed this protected mice from the negative effects of an unhealthy diet.

“These initial findings are exciting because they show we can potentially use peptides to address chronic diseases from diabetes to obesity to depression — all of which have been linked to the health of our microbiome over decades of research,” Masson said. Critically, while certain genetic strains of mice gained benefit from the defensin peptides, others did not and were, in fact, worse off.

“This shows the importance of ‘personalised medicine’, or tailoring treatments to complement the genes of individuals rather than taking a one-size-fits-all approach to medications,” Masson said. “We need to establish how different individuals and microbiomes react to the same treatments, whether they be defensin peptides or common medications already in use.”

Masson said the team is now looking to explore these peptides in humans, measuring them in the gut and looking at the relationship with metabolic health and the microbiome.

“I’m also interested in defensins beyond diabetes,” he said. “We know the microbiome is involved in many chronic diseases like cancer; I suspect defensins could play a role in this field.”

Professor David James, joint Interim Academic Director of the Charles Perkins Centre, said the work illustrates the potential power of precision medicine.

“Our work clearly shows how manipulating the gut microbiome with these peptides benefits some but not others,” he said. “This highlights both the potential of precision medicine and the potential dangers of trying to alter our gut microbiome, such as with supplements or even fad diets, before we know more about how our bodies maintain healthy microbiomes unique to each of us.”

Image credit: iStock.com/Marcin Klapczynski