Microbial community shifts elicit inflammation in the caecal mucosa via the GPR41/43 signalling pathway during subacute ruminal acidosis.

ABSTRACT

BACKGROUND: Dietary 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. RESULTS: Ten 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. CONCLUSION: This 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.