New gut bacterial proteins target fat and blood sugar

Inside your gut, common microorganisms may be quietly shaping your metabolism.

Scientists discover Ruminococcus Torquesa widely shared gut bacteria that produces two hormone-like proteins that affect weight gain, blood sugar and bone density. After a new study Natural microbiology This shows their powerful influence on rodents. These findings could mark a new generation of microbiome-based therapies for chronic diseases such as obesity, diabetes and osteoporosis.

From gut microorganisms to metabolic regulators

“We found that the number of bacteria that produce Rordep among individuals can vary as much as 100,000 times, and people with higher bacteria tend to be thinner,” said Yong Fan, the study’s lead author and assistant professor at the Novo Nordisk Center for Basic Basic Metabolic Research at Columbia University.

The basis of this discovery is that our gut microbiota is not only a passive digestive aid. This is a dynamic biologically active system that produces compounds that can affect nearly every organ in the body through the blood or intestinal nervous system. However, most bacterial strains in the microbiome are still uncharacterized.

Now researchers show that certain strains R. Torques Release Rordep1 and Rordep2 – huge protein, partly similar to Irisin, which is the hormone released by muscles during exercise. In rodents, these bacterial peptides can improve glucose tolerance, increase insulin production, reduce fat mass, and enhance bone strength.

Microorganisms that mimic hormones

To identify these peptides, the team combed through nearly 286,000 bacterial genomes to find gene sequences similar to human hormones. They’re in R. Torquesa protein encoding a protein with two fibronectin domains – a structure is also found in iris proteins. These two domains are cut into Rordep1 and Rordep2 and released into the intestine.

These peptides were confirmed in human plasma using high-precision mass spectrometry. Levels vary widely between individuals, but the presence of peptides and the bacteria that produce them are always associated with low body fat and BMI.

Signals and hormone transfer of fat burning

In mice fed a high-fat diet, oral delivery of Lordep bacteria reduced fat gain and enhanced expression of genes involved in heat production, a process by which calories are produced by burning calories. Injection of purified Rordep1 in rats resulted in a range of hormone effects: insulin, GLP-1 and PYY levels increased, while appetite-promoting hormone GIP decreased.

“In experiments with rats and mice that received the gut bacteria that produce Rordep or the Rordep protein itself, we observed a decrease in weight gain, a decrease in blood sugar levels, and an increase in bone density,” Yong Fan said. “It’s exciting that this is the first time we mapped the gut bacteria to change the hormone balance.”

Human trials and future therapies

These results have been quickly transferred from the laboratory to the clinic. Researchers at the University of Copenhagen have launched two clinical trials in collaboration with several hospitals and Novo Nordisk. One person tested the effect of real-time Lodep bacteria in healthy volunteers. Another investigated the role of the Rordep1 protein in purified form.

Professor Oluf Pedersen, senior author and project leader, said: “We are now converting basic research into human research to explore whether the bacteria or Rordep protein that produces Rordep (in its natural or chemically modified form) can be used as the basis for a new biological drug called a drug.”

Pedersen is also the founder of Gutcerine, a spinning biotechnology supported by the University of Copenhagen. The company aims to develop these findings into second-generation probiotics and therapeutic peptides that can one day treat or prevent cardiac metabolic diseases.

Gaze at the microbial medicine cabinet

The idea of gut-derived therapeutic agents is nothing new, but this work makes it more focused. Rordeps are full-length peptides, rather than small molecules, that act more like hormones than typical bacterial metabolites. They act systematically, at least in rodents that can reconnect liver metabolism, inhibit fat storage and regulate blood sugar.

Human experiments will determine whether these effects continue to people. If you do so, it may change our perception of the microbiome, not as a contribution to health, but as a source of programmable, precise therapies that apply metabolic balance.

Journal Reference

Natural microbiology (2025). doi:10.1038/s41564-025-02064-x

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