Researchers at the University of Konstanz have demonstrated at a molecular level how bacteria in the human gut influence the entire body. Among other things, they can lower blood sugar levels and reduce fatty liver disease.

For several years now, a wide range of over-the-counter products have been available that are designed to have a positive effect on the gut microbiome. They promise greater bacterial diversity in the digestive tract and, as a result, better overall health. For the same purpose, doctors prescribe medications aimed at restoring gut microbial balance, for instance following antibiotic treatment. But why does the gut microbiota have such a profound impact on the entire organism? Thomas Brunner, professor of biochemical pharmacology, and biologist Anna Pia Plazzo at the University of Konstanz set out to answer this question. Together with their team, they recently discovered that gut bacteria and the compounds they produce – which also enter the food chain via ruminants – trigger biological processes that the human body on its own can only activate with difficulty. They help suppress inflammation and may also have beneficial effects on fatty liver disease.

In his research, Brunner investigated a specific transcription factor, the nuclear receptor LRH-1/NR5A2. This receptor plays an important role in the regulation of inflammatory and metabolic diseases and also influences tumour development. However, to carry out its functions, it must first be "activated". This activation occurs when specific molecules known as ligands bind to the receptor. More than two decades ago, researchers discovered that the LRH-1 receptor is present in the intestine and the liver, too. Yet the ligand responsible for its activation remained elusive. This raised an important question: what activates LRH-1 in these organs?

"For many nuclear receptors, the ligands required are known, such as thyroid hormones. These receptors can be specifically regulated or activated. LRH-1, however, does not have a clearly defined ligand produced by the body. And if it doesn’t come from the body itself, the source is likely another resident of the gut: its bacterial community", explains Brunner.

Through a series of experiments and analyses, he and his team eventually found that probiotic bacteria do indeed produce molecules that act as ligands for the LRH-1 receptor. The key substance in question is vaccenic acid, which, however, is not naturally present in the human body. "Vaccenic acid is produced by bacteria that live in ruminants. During the rumination process, the bacteria generate this fatty acid, which is subsequently distributed throughout the animal’s body, including its muscle tissue and milk. When we consume foods such as meat and dairy products from ruminants, vaccenic acid reaches our intestine, where it can continue to exert its beneficial effects", Brunner explains.

Further experiments in mice revealed that vaccenic acid can improve a variety of health-related markers. Blood sugar and blood lipid levels fell significantly in the tests, and an existing fatty liver condition improved. "The administration of vaccenic acid ultimately has a therapeutic effect on the body’s entire metabolism, as it activates the transcription factor LRH-1", says Brunner, summarizing the findings.

For the first time, the researchers identified a bacterial ligand capable of activating the transcription factor LRH-1. Yet, according to Brunner, their study illustrates even more: "An imbalance in the gut microbiome may have a huge impact on the whole body. "Our research shows, at the molecular level, how an intact microbiome releases substances that regulate physiological processes in the body and thus positively influence overall metabolism." Key facts:

• Original publication: Plazzo, A. P., Filz, V., Prothiwa, M. et al. Microbiome-host communication via vaccenic acid modulates LRH-1/NR5A2 activity and ameliorates metabolic liver disease. EMBO Mol Med (2026). DOI: https://doi.org/10.1038/s44321-026-00516-3
• Thomas Brunner is a professor of biochemical pharmacology at the University of Konstanz. His main areas of focus include application-oriented basic research in the fields of tumour biology, immunology and cell biology.
• Dr Anna Pia Plazzo is a biologist at the University of Konstanz and coordinates the "Death Decisions" graduate school within the Transregional Collaborative Research Centre SFB-TRR 353.