Summary: | <i>Salmonella</i> spp. Remains a major public health problem globally. Biomedicine is the cornerstone of modern health care and could be a solution for antibiotic-resistant <i>Salmonellosis</i>. Although postbiotics seem to be an effective treatment in various clinical conditions, their clinical effects on <i>Salmonella</i> colitis have not been reported. Our previous report revealed that active vitamin D attenuates the severity of <i>Salmonella</i> colitis and invasiveness by reducing inflammation and enhancing the production of antimicrobial peptides. Therefore, we investigated the synergistic effects of butyrate, the most studied postbiotic, and active vitamin D on the severity of <i>Salmonella</i> colitis, invasiveness of <i>Salmonella</i>, and host immune responses, as well as its novel mechanisms, using in vitro and in vivo studies. We demonstrated that a combination of butyrate and active vitamin D (1 alpha, 25-dihydroxyvitamin D3) synergically reduced the severity of <i>Salmonella</i> colitis in C57BL/6 mice and reduced cecal inflammatory mIL-6, mIL-8, mTNF-α, and mIL-1β mRNA expression, but enhanced the antimicrobial peptide mhBD-3 mRNA, compared to a single treatment. Additionally, upregulated vitamin D receptor (VDR) plays a critical role in the synergistic effects. This suggests combined benefits of butyrate and active vitamin D on <i>Salmonella</i> colitis through VDR-mediated antibacterial and anti-inflammatory responses. The combined use of both supplements could be a potential biomedicine for infectious and autoimmune colitis.
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