Gut health is often marketed as being shaped mainly by diets and supplements, but new research from the University of Sydney shows our genes play a direct role too. The study, published in EMBO J and led by Dr. Stewart Masson from the Charles Perkins Centre, found that certain genes in mice produce natural peptides called alpha-defensins, which act like gardeners by encouraging beneficial microbes and suppressing harmful ones. Since humans also produce alpha-defensins, the findings highlight that our bodies actively influence the microbiome, challenging the view that gut health is determined solely by diet.

The study revealed that mice with these genes developed healthier microbiomes and were far less prone to insulin resistance, a major driver of type 2 diabetes and heart disease. According to Professor David James, joint Interim Academic Director of the Charles Perkins Centre, the findings suggest that our DNA actively shapes gut health, and these microbial-regulating peptides could one day be harnessed as a potential tool against obesity and diabetes.

While investigating genetic factors behind insulin resistance in mice, researchers discovered that those less prone to the condition carried genes altering the production of defensin peptides in intestinal cells. Dr. Masson explained that defensin peptides, found across organisms from plants to humans, are considered early precursors of the immune system, with mice and humans evolving many variants to help defend against diverse threats. The study showed that mice producing higher levels of alpha-defensins were notably healthier than those with lower production.

To validate their findings, researchers synthesized defensin peptides in the lab and gave them to mice lacking the relevant genes, which protected the animals from the harmful effects of an unhealthy diet. Dr. Masson noted that this opens the door to using peptides as potential treatments for chronic diseases such as diabetes, obesity, and depression, all long linked to microbiome health. However, the study also revealed that while some genetic strains of mice benefited, others worsened, underscoring the need for personalized medicine tailoring therapies to individual genetic and microbiome differences rather than relying on one-size-fits-all treatments.

Source:https://www.sydney.edu.au/news-opinion/news/2025/09/11/genes-prune-gut-microbiome-to-protect-from-chronic-disease-diabetes-depression.html