Short-chain fatty acids in ulcerative colitis: integrating metabolic fate, dynamic biomarkers, and precision delivery

Ulcerative colitis (UC) is characterized by gut dysbiosis and impaired mucosal metabolism, positioning short-chain fatty acids (SCFAs) as pivotal mediators. This review moves beyond general mechanisms, offering an in-depth analysis of SCFA metabolic fate, including specific transporters (e.g., monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1)), the concept of "colon fuel priority," and their systemic distribution bypassing first-pass hepatic metabolism to reach distant organs. We integrate the established role of SCFAs in modulating immunity and barrier function with their significant but lesser-discussed effects on attenuating oxidative stress and regulating colonic motility. Crucially, we highlight SCFAs' emergence as dynamic metabolic "fingerprints" with significant diagnostic and prognostic potential, offering advantages over conventional inflammatory markers. The therapeutic section emphasizes novel strategies, from microbiota-targeted approaches to the urgent need for efficient, site-specific delivery systems. By systematically bridging deep mechanistic understanding, biomarker utility, and innovative delivery platforms, this review advances SCFA-centered nutritional strategies toward precise and individualized management of UC.