What is it about?
Sepsis is a life-threatening reaction to infection that still kills millions of people every year. Our gut bacteria produce small molecules called short-chain fatty acids; one of them, butyrate, calms inflammation, supports the immune system and keeps the intestinal wall tight. We reviewed all available experimental and clinical studies on butyrate in sepsis. In animal models, butyrate protected the brain, liver, gut, heart, lungs and kidneys, mainly by reducing inflammation, oxidative stress and barrier damage, and improved survival by 20-40%. Human data are still scarce but encouraging: sepsis survivors had higher levels of a related molecule, and a trial using synbiotics that raised butyrate showed fewer gut complications and ventilator-associated pneumonias.
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Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
Despite better antibiotics and intensive care, there is no specific drug that corrects the harmful immune response in sepsis. Butyrate is cheap, naturally produced in the gut and acts on several key mechanisms at once, making it an attractive add-on therapy. This review brings together the scattered preclinical evidence, highlights the gaps, and outlines what early-phase clinical trials should test: safety, dose, route and real benefit for patients.
Perspectives
As infectious diseases physicians we focus on killing the pathogen, but in sepsis the host response is often what kills the patient. The gut microbiota is a forgotten organ in critical illness. I hope this review stimulates the first well-designed clinical trials of butyrate supplementation in septic patients. It was also a pleasure to coordinate a multidisciplinary group from Trieste, Iran, Slovenia and other Italian centres.
Professor Stefano Di Bella
Universita degli Studi di Trieste
Read the Original
This page is a summary of: Therapeutic potential of butyrate supplementation in sepsis: a review of preclinical evidence and translational perspectives, European Journal of Pharmacology, February 2026, Elsevier,
DOI: 10.1016/j.ejphar.2026.178594.
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