Results: In comparison with placebo, sodium-butyrate supplementation significantly decreased the ESR level (−6.66 ± 1.56 vs. 3.00 ± 2.11, p=0.01), NLR (−0.24 ± 0.1 vs. 0.33 ± 0.23, p=0.02), Mayo score (−2.33 ± 0.41 vs. 0.22 ± 0.40, p < 0.001), HADS anxiety score (−2.77 ± 0.64 vs. 0.94 ± 0.63, p=0.001), HADS depression score (−2.38 ± 0.47 vs. 0.61 ± 0.33, p < 0.001), and GHQ total score (−12.11 ± 1.48 vs. 3.55 ± 1.39, p < 0.001). The gene discussed is ESR1; the disease is major depressive disorder.