The Synergistic Effects of Probiotics and Active Vitamin D3 on Innate Immunity to Salmonella Infection via Vitamin D Receptor

Salmonella spp. remains a major public health problem for the whole world. Intestinal epithelial cells (IECs) serve as an essential component of the mucosal innate immune system to defend against Salmonella infection. Although probiotics seem to be an effective treatment in various clinical conditions, their clinical effect on Salmonella colitis are controversial due to the specific mechanisms responsible for the effect are not fully understood. We demonstrated that probiotics differentially regulates IL-8 expression via PI3K and NOD2 signaling in Salmonella-infected IECs (Benef Microbes 2016). Recent research has begun to unravel important roles of vitamin D in the regulation of innate immunity. In response to bacterial pathogens, the innate immune response includes the production of antimicrobial peptides (AMPs) and autophagy expression. Our recent studies (Huang, FC, Clin Exp Immunol 2016 & World J Gastroenterol 2016) illustrated that enhanced AMPs and autophagy expression in Salmonella-infected intestinal epithelial cells (IECs) by active vitamin D protected the host against infection, while downregulated proinflammatory responses (IL-8 & IL-1) prevented the host from the detrimental effects of overwhelming inflammation, via PI3K, NOD2, Atg16L1 and vitamin D receptor (VDR). Probiotics increased VDR protein expression in both mouse and human IECs and VDR pathway is required for probiotic protection in colitis. In our preliminary study observed probiotic alone enhanced autophagy expression and in combination with active vitamin D3 synergistically increased hBD-2 but decreased IL-1 expression in Salmonella-infected IECs. Therefore, we investigated the synergistic effects of probiotics and active vitamin D on Salmonella colitis and invasiveness as well as its novel mechanisms by in vitro and in vivo studies. Our 3-year project will investigate: (1) the synergistic effects of probiotics and active vitamin D on autophagy, antimicrobial peptides and anti-inflammatory responses in Salmonella-infected IECs; (2) the synergistic effects of probiotics and active vitamin D on Salmonella colitis and invasion in mice; (3) the involvement of VDR on the synergistic effects of probiotics and active vitamin D on innate immunity to Salmonella infection in mice.

Project ID:PC10608-2357
External Project ID:MOST106-2314-B182-052