Inflammatory bowel diseases occur when the delicate balance between the gut, the immune system, and the microbiota is disrupted. Until now, however, it was unclear whether harmful microbes or defects in the body’s own immune cells were the primary cause of these diseases.
A research group led by Dr Mauro Corrado at the University of Cologne’s CECAD Cluster of Excellence for Aging Research and the Center for Molecular Medicine Cologne (CMMC) has now discovered that a specific lipid known as cardiolipin, which is found in the mitochondria, is essential for keeping the immune response in the gut under control. Cardiolipin helps regulatory T cells maintain the energy and stability they need to prevent inflammation. Regulatory T cells are a specific group of immune cells that have an immunosuppressive effect, meaning they suppress certain immune system responses. They produce molecules (cytokines) that regulate other immune cells and prevent them from triggering an excessive inflammatory response. The study “Cardiolipin preserves Treg metabolic fitness and immune homeostasis in the gut” was published in the Nature Metabolism journal.
In a mouse model, those animals whose T cells had been stripped of the enzyme required to produce cardiolipin developed inflammation in the gut. This occurred regardless of changes in the microbiota. When they were then exposed to gut bacteria that are usually harmless, the inflammation progressed more rapidly and became more severe. Without cardiolipin, the T cells lose their metabolic fitness and trigger a stress response that causes diseases. However, this effect is reversible: once this stress response was corrected, gut balance was restored and the mice enjoyed a longer lifespan. For the study, the researchers combined modern immunology with state-of-the-art lipidomics and metabolic approaches.
“These findings offer a new perspective on inflammation,” says Corrado, Principal Investigator at CECAD. “We believe that targeting the metabolism of immune cells specifically could be a fundamentally new approach to treating inflammatory bowel diseases.”
The study suggests that metabolism influences our immune response. Individual differences in the metabolic efficiency of immune cells explain, at least in part, the varying clinical courses of diseases caused by the same pathogen. Although the study examines only a single metabolic defect, this specific aspect could be another piece of the puzzle, providing new insights into the broader question of why infections often progress in very different ways. Experience with COVID-19 and many other infectious diseases has shown that a pathogen can cause a wide range of symptoms and disease outcomes, from mild to severe to fatal. It is not yet fully understood why some people are more susceptible, and others less susceptible, to these pathogens. To gain a better understanding of how these various factors interact, the research will be expanded to include other mitochondrial defects.
The findings could also help explain the gastrointestinal symptoms associated with Barth syndrome, an extremely rare genetic disorder caused by a deficiency of cardiolipin. The study showed that patients suffering from Barth syndrome not only have life-threatening heart conditions, they also suffer from immune system disorders. They are more susceptible to returning infections and gastrointestinal disorders. This could be explained, at least in part, by the T-cell deficiencies detected in patient samples.
Nature Metabolism
Experimental study
Animals
Cardiolipin preserves Treg metabolic fitness and immune homeostasis in the gut
18-May-2026