Microbial community shifts elicit inflammation in the caecal mucosa via the GPR41/43 signalling pathway during subacute ruminal acidosis
Microbial community shifts elicit inflammation in the caecal mucosa via the GPR41/43 signalling pathway during subacute ruminal acidosis
复制标题
亚急性瘤胃酸中毒期间微生物群落变化通过 GPR41/43 信号通路引发盲肠粘膜炎症
DOI：
10.1186/s12917-019-2031-5
复制
发表时间：
2019-08-19
影响因子：
2.6
通讯作者：
Shen, Xiangzhen
中科院分区：
文献类型：
--
作者：
Chang, Guangjun;Zhang, Huanmin;Shen, Xiangzhen
反刍动物的日粮结构与胃肠道微生物群的组成密切相关。综合研究表明，饮食诱导的SARA可引起盲肠内微生物群落的改变，从而引起局部炎症。然而，反刍动物肠道微生物菌群变化引发盲肠炎症的机制在很大程度上是未知的，以及这种炎症的发展是否受到表观遗传修饰的影响。结果将10只产乳山羊随机分为2组，分别饲喂低精料饲粮（LC，精料40%，n= 5）和高精料饲粮（HC，精料60%）诱导亚急性瘤胃酸中毒（SARA）。与LC相比，hc诱导的SARA改变了主要的门和属，从而增加了脂多糖（LPS）和短链脂肪酸（SCFAs）的浓度。同时，hc诱导的SARA提高了细胞因子和趋化因子mRNA的表达以及GPR41、GPR43、p38和ERK1/2 mRNA和蛋白的表达，而hc诱导的SARA对TLR4和p65无影响。此外，hc诱导的SARA降低了GPR41和GPR43启动子区域染色质压实和DNA甲基化的百分比。结论HC饮食诱导的SARA引起盲肠菌群组成的改变。这种改变增加了LPS的浓度，但由于肠上皮细胞对一定水平LPS的耐受作用，不能激活TLR4信号通路，同时升高了SCFAs的浓度，从而激活GPR41和GPR43信号通路，产生细胞因子和趋化因子，引起盲肠炎症。表观遗传机制促进了这种炎症在患SARA的哺乳期山羊中的发展。
BackgroundDietary structure in ruminants is closely connected with the composition of gastrointestinal microbiota. Merging study has shown that dietary induced SARA causes the alteration of microbial community in the cecum leading to the local inflammation. However, the mechanisms of cecum inflammation elicited by the shift of microbial flora in ruminants are largely unknown, and whether the development of this inflammation is modified by epigenetic modifications.ResultsTen multiparous lactating goats were randomly seperated into two groups and received either a low concentrate diet (LC, 40% concentrate,n= 5) or a high concentrate diet (HC, 60% concentrate) to induce subacute ruminal acidosis (SARA). Compared with LC, HC-induced SARA altered the predominant phyla and genera, thereby increasing the concentration of lipopolysaccharide (LPS) and short chain fatty acids (SCFAs). Meanwhile, HC-induced SARA enhanced the mRNA expression of cytokines and chemokines and the expression of mRNA and protein of GPR41, GPR43, p38 and ERK1/2, while HC-induced SARA had no effect on TLR4 and p65. Furthermore, HC-induced SARA decreased the percentage of chromatin compaction and DNA methylation at the area of the promoters of GPR41 and GPR43.ConclusionThis study indicated that HC diet induced SARA resulted in the alteration in the composition of cecal microbiota. This alteration increased the concentration of LPS, but failing to activate TLR4 signaling pathway due to the tolerance effect of intestinal epithelial cell to certain level of LPS, as well as elevated the concentration of SCFAs, thereby activating GPR41 and GPR43 signaling pathway to produce cytokines and chemokins and cause the cecal inflammation. And epigenetic mechanisms contributed to the development of this inflammation in the lactating goats suffering from SARA.