Adaptation to High Grain Diets Proceeds Through Minimal Immune System Stimulation and Differences in Extracellular Matrix Protein Expression in A Model of Subacute Ruminal Acidosis in Non-lactating Dairy Cows

Abstract

Problem statement: Subacute Ruminal Acidosis (SARA) is a metabolic disorder affecting approximately 20% of all dairy cattle in North America. Although the presence of SARA has been described for some time, the etiology of the disorder remains uncertain. For example, many animals diagnosed with SARA seem to remodel and adapt their epithelium to accommodate the stresses imposed by SARA, but not before exacting a significant health and economic toll. Specifically, a search is on in which a desire to identify the system and associated pathways that are causative agents in the progression and development of SARA is evident. We hypothesize that adaptation to SARA is facilitated by the immune system. Approach: In order to answer of this question, 4 mature, nonlactating dairy cattle were transitioned from a High Fiber (HF; 0% grain) diet to High Grain (HG; 65% grain) diet. Having fed the HG diet for three weeks, the cattle were then transitioned back to the HF diet for an additional three weeks to facilitate adaptation. SARA was diagnosed by pH data only during the first week and not during the remaining weeks, indicating that adaptation to the HG diet took place within one week. Results: In this study, significant (p<0.05) extracellular matrix protein changes (COL4A1, LAMB1) were seen during this study indicating a change in matrix architecture to facilitate adaptation. In addition, similar significant (p<0.05) patterns of expression of inflammatory cytokines and mediators of the LPS-mediated toll-like receptor pathway were seen. Conclusion: These results indicate that the immune system is involved in the adaptation of the rumen epithelium to a HG diet, but to a lesser extent than was previously thought. This is the first time an attempt has been made to link the immune system and wound healing in the adaptation of the bovine rumen to a HG diet.

Butyrate-Mediated Genomic Changes Involved in Non-Specific Host Defenses, Matrix Remodeling and the Immune Response in the Rumen Epithelium of Cows Afflicted With Subacute Ruminal Acidosis

“…In addition, SAA, also an acute phase protein, was unaffected by the addition of butyrate. Together, the data for LPS, LBP and SAA contradict earlier findings using similar models (Dionissopoulos et al, 2012a;2012b), that although SARA can have profound effects on the physiology of the rumen, the bacterial overgrowth that typically occurs is not sufficient enough to result in a systemic inflammatory response. The tissue signals generated as a result of SARA at the site of tissue damage (Steele et al, 2011a) likely act locally in an autocrine or paracrine manner.…”

“…SARA does this by causing a sloughing of the rumen epithelium, compromising epithelial integrity (Steele et al, 2011a). Despite the fact that the transmigration of microbes across the rumen wall has been documented in cases of SARA, we have shown that this effect involves the immune system, although the extent of immune system stimulation is limited to local events and is not detectable systemically (Dionissopoulos et al, 2012a;2012b). Experimentally, we have shown that adaptation to a SARA diet takes place within three weeks (Steele et al, 2011a) and previous experiments have shown that one of the principle methods by which the rumen adapts to an acidotic diet is by increasing papillae size and thus the total absorptive surface area of the rumen (Gabel et al, 2002), by increasing cellular turnover and an overall increase in total epithelial cell number (Goodlad, 1981).…”

Analysis of the gut bacterial communities in beef cattle and their association with feed intake, growth, and efficiency1,2,3

“…Conditions such as acidosis have distinct influences on health and production due to shifts in ruminal and lower gastrointestinal (GI) microbial communities, ruminal fermentation, and ruminal and lower GI function, of which the microbiome and ruminal epithelia have been shown to acclimate in response to SARA (McCann et al, 2016). In turn, acclimation to SARA is facilitated by and linked to the immune system, through crosstalk of inflammatory mediators, endotoxins, epithelial remodeling, and microbial interactions (Dionissopoulos et al, 2012). Crosstalk mechanisms regarding the gut-brain axis are also associated with the potential to affect behavior, through nutritional effects on microbial ecology, ruminal fermentation and morphology, GI inflammation, barrier function, and epithelial gene expression (Devant et al, 2016).…”