Abstract
Subacute ruminal acidosis (SARA) is known to trigger a systemic inflammatory response that is possibly caused by the translocation of lipopolysaccharides (LPS) from the gastrointestinal tract into the bloodstream. The aim of this study is to investigate this causal relationship between the increases of circulating LPS and liver inflammation. Here we found that SARA goats exhibited significantly increased LPS concentrations in both the rumen and portal vein. The livers of these goats exhibited increased mRNA concentrations of pro-inflammatory genes that indicated inflammation. Meanwhile, the occurrence of liver inflammation was further validated by the enhanced protein expression of those cytokines in the livers of SARA goats. These increased expressions of detected pro-inflammatory genes were likely mediated by enforced TLR4 signaling because SARA increased the concentrations of TLR4 mRNA and protein in the liver and the abundance of both the NF-kB-p65 factor and its active phosphorylated variant. We also verified that the enhanced TLR4 expression was accompanied by chromatin decompaction and demethylation of the proximal TLR4 promoter. Hence, epigenetic mechanisms are involved in the enforced expression of immune genes during SARA, and these findings open innovative routes for interventions via the modulation of these epigenetic mechanisms.
Highlights
Subacute ruminal acidosis (SARA) has become the primary metabolic disease in dairy industry and has received increasing attention over the last decade [1,2,3]
The consumption of the HC diet caused a gradual decline in the average daily rumen pH in the treatment group from 6.54 in the 1st week to 5.63 in the 8th week, whereas the pH remained stable and above 6.2 in the control group beginning in the 1st week (Figure 1)
In accordance with previous research [3, 10, 26], we observed that experimentally-induced SARA reduced the milk yield and milk fat percentage in the goats fed the HC diet compared with the goats fed the LC diet, the energy and protein levels were similar between the groups
Summary
Subacute ruminal acidosis (SARA) has become the primary metabolic disease in dairy industry and has received increasing attention over the last decade [1,2,3]. The persistent consumption of a high-concentrate (HC) diet by ruminants increases the production of organic acids and causes a depression of the pH in the digestive tract [2,3,4]. This decrease in pH may result in alterations of the type of fermentation and the composition of the microbiota in the rumen. Together, these changes can eventually lead to the accumulation of lipopolysaccharides (LPS), and may concomitantly disrupt the gastrointestinal barrier and facilitate the translocation of LPS from the digestive tract into bloodstream [5,6,7]. The translocation of LPS from the digestive tract into the bloodstream often triggers a systemic inflammatory response [10,11,12]
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