Inside your gut, a common microbe may be quietly shaping your metabolism.
Scientists have discovered that Ruminococcus torques, a widely shared gut bacterium, produces two hormone-like proteins that influence weight gain, blood sugar, and bone density. These tiny polypeptides, named RORDEP1 and RORDEP2, are now the subject of human trials, following a new study in Nature Microbiology that shows their powerful effects on rodents. The findings could mark the beginning of a new generation of microbiome-based treatments for chronic diseases like obesity, diabetes, and osteoporosis.
From Gut Microbe to Metabolic Regulator
“We found that the number of RORDEP-producing bacteria can vary by up to 100,000 times between individuals, and that people with high levels of these bacteria tend to be leaner,” said Yong Fan, lead author of the study and assistant professor at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.
The discovery builds on the idea that our gut microbiota is not just a passive digestive aid. It is a dynamic, bioactive system producing compounds that can affect nearly every organ in the body, either through the bloodstream or the gut’s nervous system. Yet, most bacterial strains in the microbiome remain uncharacterized.
Now researchers have shown that certain strains of R. torques release RORDEP1 and RORDEP2—small proteins that partly resemble irisin, a hormone released by muscle during exercise. In rodents, these bacterial peptides improve glucose tolerance, increase insulin production, reduce fat mass, and enhance bone strength.
The Hormone-Mimicking Microbe
To identify these peptides, the research team combed through nearly 286,000 bacterial genomes, looking for gene sequences that resembled human hormones. They found a standout in R. torques, encoding a protein with two fibronectin domains—structures also found in irisin. The two domains are cleaved into RORDEP1 and RORDEP2 and released into the gut.
These peptides were confirmed in human blood plasma using high-precision mass spectrometry. Levels varied widely between individuals, but presence of the peptides and the bacteria that produce them were consistently linked to lower body fat and BMI.
Fat-Burning Signals and Hormonal Shifts
In mice fed a high-fat diet, oral delivery of live RORDEP-producing bacteria reduced fat gain and boosted expression of genes involved in thermogenesis, the process of burning calories to generate heat. Injections of purified RORDEP1 in rats led to a cascade of hormonal effects: insulin, GLP-1, and PYY levels rose, while the appetite-promoting hormone GIP dropped.
“In experiments with rats and mice that received either RORDEP-producing gut bacteria or the RORDEP proteins themselves, we observed reduced weight gain and lower blood sugar levels, along with increased bone density,” said Yong Fan. “What’s exciting is that this is the first time we’ve mapped gut bacteria that alter our hormonal balance.”
Human Trials and Future Therapies
These results have moved quickly from lab to clinic. Researchers at the University of Copenhagen, in collaboration with several hospitals and Novo Nordisk, have launched two clinical trials. One tests the impact of live RORDEP-producing bacteria in healthy volunteers. The other investigates the effects of RORDEP1 protein in its purified form.
“We’re now translating our basic research into human studies to explore whether RORDEP-producing bacteria or the RORDEP proteins—either in their natural or chemically modified form—can serve as the foundation for a new class of biological drugs known as pharmabiotics,” said Professor Oluf Pedersen, senior author and project leader.
Pedersen is also a founder of GutCRINE, a spin-out biotech backed by the University of Copenhagen. The company aims to develop these findings into second-generation probiotics and therapeutic peptides that could one day treat or prevent cardiometabolic diseases.
Peering into the Microbial Medicine Cabinet
The idea of gut-derived therapeutics isn’t new, but this work brings it into sharper focus. RORDEPs are full-length peptides, not small molecules, and they function more like hormones than typical bacterial metabolites. They act systemically and, at least in rodents, can rewire the liver’s metabolism, suppress fat storage, and regulate blood glucose.
Human trials will determine whether these effects carry over to people. If they do, it could shift how we think about the microbiome—not just as a contributor to health, but as a source of programmable, precision therapies tailored to metabolic balance.
Journal Reference
Nature Microbiology (2025). DOI: 10.1038/s41564-025-02064-x
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