Effects of Short Chain Fatty Acid‐Butyrate Supplementation on the Disease Severity, Inflammation, and Psychological Factors in Patients With Active Ulcerative Colitis: A Double‐Blind Randomized Controlled Trial

<b>Background:</b> Depression and anxiety are common in UC patients due to gut microbiota dysbiosis and increased proinflammatory markers. Butyrate, a short-chain fatty acid, participates in the regulation of gut microbiota and inflammation and has neuroprotective effects in neurodegenerative disease. Therefore, we assessed the effects of sodium butyrate supplementation on the disease severity, inflammation, and psychological factors in active UC patients. <b>Methods:</b> This study was a randomized, parallel, double-blind controlled trial. Participants in the intervention (<i>n</i> = 18) and control (<i>n</i> = 18) groups received 600 mg/kg of sodium butyrate or rice starch as a placebo with their main meal, respectively, for 12 weeks. The partial Mayo score was used to evaluate disease severity, while the Westergren method was employed to assess the erythrocyte sedimentation rate (ESR). NLR and PLR were determined using an automated analyzer (XS-500i, Sysmex). Moreover, the psychological factors were assessed by the hospital anxiety depression scale (HADS) and the general health questionnaire (GHQ). <b>Results:</b> In comparison with placebo, sodium-butyrate supplementation significantly decreased the ESR level (-6.66 ± 1.56 vs. 3.00 ± 2.11, <i>p</i>=0.01), NLR (-0.24 ± 0.1 vs. 0.33 ± 0.23, <i>p</i>=0.02), Mayo score (-2.33 ± 0.41 vs. 0.22 ± 0.40, <i>p</i> < 0.001), HADS anxiety score (-2.77 ± 0.64 vs. 0.94 ± 0.63, <i>p</i>=0.001), HADS depression score (-2.38 ± 0.47 vs. 0.61 ± 0.33, <i>p</i> < 0.001), and GHQ total score (-12.11 ± 1.48 <i>vs</i>. 3.55 ± 1.39, <i>p</i> < 0.001). <b>Conclusion:</b> Butyrate could serve as an effective adjuvant treatment for reducing disease severity and alleviating psychological symptoms. This trial was registered on the Research Ethics Committee of Shiraz University of Medical Sciences, with the reference number IR.SUMS.SCHEANUT.REC.1400.037. <b>Trial Registration:</b> Iranian Registry of Clinical Trials: IRCT20211214053401N1.