A high-concentrate diet induced colonic epithelial barrier disruption is associated with the activating of cell apoptosis in lactating goats

Background: In ruminants, lower ruminal pH causes massive disruption of ruminal epithelial structure during periods of feeding high-concentrate diets. However, the influence of excessive organic fatty acids in the lumen of hindgut on the epithelial structure is unclear. In this study, twelve mid-lactating goats were randomly assigned to either a HC diet group (65% concentrate of dry matter; n = 6) or a LC diet group (35% concentrate of dry matter; n = 6) for 10 weeks. The colonic epithelial structure was detected by HE staining and transmission electron microscopy (TEM), and the apoptotic status of epithelial cells was estimated by TUNEL method and caspase activities. Results: HC goats showed higher level of free lipopolysaccharide (LPS) in rumen fluid (p < 0.01) but not in colonic digesta (p > 0.05), and higher total volatile fatty acid (VFA) concentrations in rumen fluid (p < 0.05) and in colonic digesta (p < 0.01), and higher content of starch in colonic digesta (p < 0.05) compared to LC goats. HC goats demonstrated profound alterations in the colonic epithelial structure and tight junctions (TJ), apparently due to damage of the epithelium with widened TJs space and nuclear breakdown and mitochondrial swelling. HC goats showed higher level of apoptosis in the colonic epithelium with higher proportion of TUNEL-positive apoptotic cells and increases of caspase-3 and -3/7 activities, as well as the lower ratio of bcl-2/bax mRNA expression in the colonic mucosa (p < 0.05). However, beta-defense mRNA was significantly down-regulated in the colonic mucosa of HC goats compared to LC (p < 0.05). HC goats showed higher level of TJ proteins including claudin-1 and claudin-4 in the colonic mucosa than LC (p < 0.05). Neither free LPS content in the colonic digesta nor NF-kappa B protein expression in tissues showed significant difference between HC and LC goats (p > 0.05). Conclusions: Our results reveal that long-term feeding HC diet to lactating goats causes severe damages to the colonic mucosa barrier associated with activating cells apoptosis.