Butyrate Impedes the Recruitment of MDSCs to Alleviate CAC Development by Inhibition of the TLR2/MyD88/NF-κB Signaling Pathway

Background: The colitis-associated colorectal cancer (CAC) with inflammatory bowel disease (IBD) serving as its prelude often has a poor prognosis due to the hysteretic diagnosis. As a representative of short chain fatty acids (SCFAs), butyrate has been proved to have obvious antitumor effect. Here, we aimed to examine its effect on CAC and possible mechanism in tumor microenvironment (TME).Method: The establishment of CAC mouse model was mainly based on the combination of AOM intraperitoneal injection and DSS three cycle. HE staining was used to analyze the degree of colonic inflammation and tumor dysplasia. The proportion of MDSCs population was mainly evaluated by flow cytometry assay. RT-PCR, immunohistochemical staining and western blot analysis was carried out to detect protein molecular expression.Results: In our current study, the AOM-DSS induced CAC mouse model was utilized to evaluate the effect of butyrate on CAC. The administration of butyrate significantly improved the weight loss, falling survival rate, higher DAI index and anal prolapse caused by the AOM-DSS during the CAC modeling process. Anatomical results including the size and number of tumors and histological results including the abnormal hyperplasia shown by HE staining also confirmed the inhibitory effect of butyrate on CAC. In addition, the proportion of myeloid-derived suppressor cells (MDSCs) assisting tumor immune escape in tumor microenvironment (TME) decreased under the intervention of butyrate. And inflammatory mediators including CCL2, IL-6 and TNF-α in TME that induce the recruitment of MDSCs showed the same trend as MDSCs. Toll-like receptor 2 (TLR2) as a receptor molecule related to inflammation and immune function was also up-regulated in CAC, accompanied by the synchronous up-regulation of downstream Myd88 and NF-κB molecules, while the use of butyrate significantly inhibited the up-regulation of these molecules.Conclusions: Butyrate might reduce the release of CCL2, IL-6 and TNF-α in TME by inhibiting TLR2/MyD88/NF-κB signaling pathway to reduce the recruitment of MDSCs in TME, which eventually weakened the immune escape of tumors and retarded the progress of CAC.

Vibrio cholerae may be transmitted to humans from bullfrog through food or water

Bullfrog is one of the most important economic aquatic animals in China. It is widely cultured in southern China, and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and even anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified from diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. At the same time, it was also found that V. cholerae may be transmitted to humans from bullfrogs through bullfrog food and aquaculture water, creating a serious threat for human health. Therefore, society should pay attention to the modes of transmission of Vibrio cholerae from bullfrog and formulate reasonable safety measures to avoid disasters.