Scientists have discovered gut bacterium proteins that may one day complement GLP-1 drugs, helping improve blood sugar control, boost fat burning, and support weight management in type 2 diabetes and obesity.
Abstract
Researchers have identified two proteins, RORDEP1 and RORDEP2, produced by certain strains of the gut bacterium Ruminococcus torques, that influence weight, blood sugar, and bone health. Preclinical studies show they increase GLP-1 and PYY, reduce GIP, boost fat burning, and improve liver insulin sensitivity. Early human trials are underway, exploring their potential as next-generation probiotics or protein-based therapies for type 2 diabetes, obesity, and related conditions.
Key Points
- RORDEP1 and RORDEP2 mimic some effects of the exercise hormone irisin and modulate key metabolic hormones.
- Animal studies show reduced weight gain, improved glucose tolerance, and stronger bones with RORDEP treatment.
- Mechanisms include increased satiety hormones, direct fat-burning effects, and improved hepatic insulin sensitivity.
- Potential therapeutic uses range from preventive probiotics to drug combinations enhancing GLP-1 therapy.
- Human trials have started, but clinical availability is likely 10–15 years away.
Scientists in Denmark and their international collaborators have discovered something remarkable in an unexpected place: the human gut. Certain strains of a common gut bacterium, Ruminococcus torques, produce two proteins named RORDEP1 and RORDEP2 that may help regulate body weight, blood sugar, and even bone health. Early research suggests these proteins could one day become part of a new class of treatments for type 2 diabetes, obesity, and related conditions.
What Makes These Proteins Special
RORDEP1 and RORDEP2 are structurally similar to irisin, a hormone released by muscles during physical activity. Like exercise, they appear to:
- Increase the body’s own production of GLP-1 and PYY, which help control appetite and blood sugar.
- Boost insulin levels after meals.
- Reduce GIP, a hormone that can promote weight gain.
- Directly enhance fat burning.
- Improve bone density in animal studies.
This combination of effects is unusual and could complement the action of GLP-1-based drugs already used in diabetes and obesity care.
From Mice to Humans
In studies with mice and rats:
- Giving RORDEP-producing bacteria or purified RORDEP1 reduced weight gain, improved blood sugar control, and increased bone strength.
- Engineered bacteria designed to make RORDEP1 had similar benefits.
- Delivering RORDEP1 directly into the gut improved the liver’s sensitivity to insulin and lowered glucose production.
Importantly, these effects seem to work through indirect signaling in the gut and bloodstream, rather than by binding directly to known hormone receptors.
Potential for Combination Therapy
Because RORDEPs work by stimulating the body’s own hormone release, they may complement drugs like semaglutide or tirzepatide, which activate hormone receptors directly. Combining the two approaches could:
- Enhance weight loss and blood sugar control.
- Reduce the dosage of GLP-1 drugs needed, potentially lowering side effects.
- Add extra benefits, such as bone protection and greater fat-burning activity.
Where Things Stand Now
The research is still in its early days:
- The first human trials are underway in Denmark—one using live bacteria that make RORDEPs, the other testing purified RORDEP1.
- It could be 10–15 years before any RORDEP-based therapy is ready for regular clinical use.
- Large-scale drug development would require chemical modification of the proteins, long-term safety studies, and significant investment.
A Long Road, but Worth Watching
While it’s too soon to know whether RORDEPs will become part of future diabetes and obesity care, the potential is clear. This research adds to the growing evidence that the gut microbiome is more than a passive passenger in human health—it may be an active partner in preventing and treating some of the world’s most common chronic diseases.
For more information, please visit Nature Microbiology and University of Copenhagen.
