The relationship between the gut microbiome and the human body is complex. While the microbes in the human gastrointestinal tract have major impact on various aspects of health, many factors can influence the gut microbiome including diet, medication, and host genetics. A new study reported in The EMBO Journal has revealed more about how host genes can affect the gut microbiome.
"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 co-corresponding study author Dr. Stewart Masson of the University of Sydney's Charles Perkins Center. "While gut microbes certainly influence everything from diabetes to depression, this study has revealed that our bodies aren't just passive hosts."
This research has used a mouse model to show that some host genes generate small proteins, or peptides called alpha-defensins. These alpha-defensin peptides seem to have a major influence on which species of gut microbes grow, and which should be eliminated. Since humans also carry alpha-defensins, the researchers suggested that these findings apply to people as well.
"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 explained.
Mice that carried alpha-defensins were found to have more diverse microbiomes with more beneficial species and and had less risk of insulin resistance compared to mice that did not.
Many defensin genes, each encoding for different peptides, have been found in mice and humans, the researchers noted. These peptides are thought to help the immune system ward off invaders. Mice with the genetic ability to produce more alpha-defensins were healthier than mice that made fewer alpha-defensins.
When mice that lacked the genes to produce alpha-defensins were given these peptides in their diets, some of the mice were shielded from the harmful effects of an unhealthy diet. (This diet was meant to mimic the Western style diet and was high in fats and sugars and low in fiber. This diet causes inflammation and obesity in mouse models.)
This benefit was only seen in mice with a certain genetic background, and not in all mice. The health of some mice actually got worse after alpha-defensin exposure.
"This shows the importance of personalized medicine, or tailoring treatments to complement the genes of individuals rather than taking a one-size-fits-all approach to medications," noted Masson. "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."
Now the investigators want to learn more about how these findings may apply to human health. They are aiming to measure alpha-defensin levels in the gut, and determine how they may affect metabolism and the gut microbiome.
The research also highlighted how precision medicine may be beneficial, but scientists and clinicians have to use caution.
"Our work clearly shows how manipulating the gut microbiome with these peptides benefits some but not others," noted co-corresponding study author Professor David James, joint Interim Academic Director of the Charles Perkins Center. "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. We are at the foothills of precision medicine, and the picture looks promising, but we have a long way to go."
Sources: University of Sydney, The EMBO Journal