20.500.12556/DiRROS-27223 Therapeutic potential of butyrate supplementation in sepsis a review of preclinical evidence and translational perspectives Sepsis remains a major global health problem and is responsible for millions of deaths annually despite significant progress in antimicrobial therapy and organ support. Increasing evidence highlights the role of the gut–immune axis in shaping host responses during sepsis, with particular interest in microbiota-derived metabolites such as short-chain fatty acids (SCFAs). Among these, butyrate has emerged as a promising candidate due to its anti-inflammatory, immunomodulatory, and intestinal barrier–preserving properties. This narrative review summarizes current evidence regarding the biological activities of butyrate and its potential therapeutic relevance in sepsis and septic shock. A comprehensive literature search of PubMed and additional sources up to April 2025 identified experimental and clinical studies evaluating butyrate supplementation in sepsis. Preclinical studies show that butyrate improves function across organ systems (neurologic, hepatic, intestinal, cardiac, pulmonary, and renal) mainly by reducing inflammation, oxidative stress, and epithelial barrier disruption. In models like cecal ligation and puncture (CLP) or endotoxemia, survival improved by 20–40 % with butyrate administration. Human data are limited: an observational study found higher circulating β-hydroxybutyrate levels in sepsis survivors, while a randomized trial reported fewer gastrointestinal complications and ventilator-associated pneumonia in patients with synbiotic-induced butyrate increases. Overall, current evidence suggests that butyrate may modulate key pathophysiological pathways in sepsis and holds potential as an adjunctive therapy. Nonetheless, dedicated early-phase clinical trials are required to clarify safety, optimal dosing, pharmacodynamics, and clinical effectiveness. butyrate gut microbiota sepsis septic shock short-chain fatty acids butirat črevesna mikrobiota sepsa septični šok kratkoverižne maščobne kisline true false true Angleški jezik Slovenski jezik Neznano 2026-01-29 11:39:52 2026-01-29 11:39:53 2026-02-01 04:07:35 0000-00-00 00:00:00 2026 0 0 Nasl z nasl. zaslona; Opis vira z dne 29. 1. 2026; str. 1-11 [article no.] 178594 Vol. 1015 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.9 1879-0712 10.1016/j.ejphar.2026.178594 266635779 RAZ_Benvenuto_Nicola_2026.pdf RAZ_Benvenuto_Nicola_2026.pdf 1 0D7B37C2BEDDF54C2BC34852A943781F 8c5e26d8ae86301d23379e16c8f5d38ca1a0b65bf890da93acb1eed2ef2e39b0 01ad4ac1-fcff-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=39672 https://www.sciencedirect.com/science/article/pii/S0014299926000762 0 0ed1e791-fcff-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=39673 Univerzitetni klinični center Ljubljana 0 0 0