By Clinical Research News Staff 

September 9, 2025 | The gut microbiome has long been recognized as a key influencer of human health, but most clinical efforts to translate that knowledge have revolved around broad dietary interventions, probiotics, or microbial metabolites. Now, a team of researchers in Denmark is taking a new route that focuses on specific bacterial proteins that may directly regulate human metabolism and advancing them into clinical testing. 

The team found that two proteins, RORDEP1 and RORDEP2, which are produced by a common gut bacterium, have shown the ability to influence weight, blood sugar, and bone density by mimicking hormone-like signals. The discovery was led by Dr. Yong Fan of the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, with results published recently in Nature Microbiology (DOI:  10.1038/s41564-025-02064-x). 

The proteins have been compared to irisin, which provides a biological anchor to the well-studied hormone “known to be released by muscles during exercise, playing a role in fat metabolism, and energy regulation,” according to Fan. By increasing hormones such as glucagon-like peptide-1 (GLP-1) and pancreatic polypeptide (PYY)—both critical to appetite, blood sugar, and insulin regulation—while reducing gastric inhibitory polypeptide (GIP), which can promote weight gain, RORDEP proteins seem to provide a multi-pronged metabolic benefit. In rodents, both introducing RORDEP-producing bacteria and administering purified proteins yielded consistent improvements in weight control and blood sugar regulation. 

The clinical implications are significant. “By uncovering RORDEP proteins, we have revealed a new layer of communication between microbes and humans, with the potential to transform how we prevent and treat some of the most pressing chronic diseases of our time,” Fan explains.  

To bring these findings into the clinic, Fan co-founded GutCRINE, a biotech spinout from the University of Copenhagen, with Professor Oluf Pedersen, senior study author and group leader at Human Genomics and Metagenomics in Metabolism, Center for Basic Metabolic Research, at the university. The company is already heading into two first-in-human trials. One involves healthy volunteers receiving live RORDEP-producing bacteria to evaluate safety and biological activity. Another study involves purified RORDEP1 protein being tested directly in humans.  

GutCRINE’s strategy is to develop two complementary therapeutic platforms. The first, described as “second-generation probiotics,” would deliver RORDEP-producing bacteria as a preventive supplement for chronic diseases. The second involves developing biological drugs based on the purified proteins, which could be prescribed as medication for conditions such as diabetes, obesity, cardiovascular disease, and osteoporosis. 

To read the full story written by Deborah Borfitz, visit Bio-IT World.