Abstract
Background: The hindgut epithelial barrier plays an important role in maintaining absorption and immune homeosrasis in ruminants. However, there is little information available on changes of colon epithelial barrier structure and function following grain-induced subacute ruminal acidosis (SARA). The objective of this study was to investigate the effects of SARA on colon epithelial morphological structure, permeability and gene expression involved in epithelial barrier function using dairy goats as a ruminant model. Methods: Twelve mid-lactating Sannan dairy goats (62.13 ± 4.76 kg) were randomly divided into either control (n = 6) or SARA treatment (n = 6). Control goats were fed a mixed diet (non-fiber carbohydrates/neutral detergent fiber (NFC/NDF) =1.15) for 60 days, SARA induction goats were given 4 mixed diets with NFC to NDF ratios of 1.15, 1.49, 2.12 and 2.66 to induce development of SARA. The duration of each diet was 15 d including 12 d for adaption and 3 d for sampling. Continuous ruminal pH recordings were utilized to diagnose the severity of SARA. Additionally, Plasma and colonic tissue were collected to evaluate the epithelial tissue morphological structure, permeability and expression of tight junction (TJ) protein using histological techniques, Ussing chamber, real-time PCR and western blotting. Results: Profound disruption in the colonic epithelium was mainly manifested as the electron density of TJ decreased, intercellular space widened and mitochondria swelled in SARA dairy goats. Epithelial Isc, Gt and the mucosal-to-serosal flux of FD4 ( P < 0.05) were increased, PD was decreased in SARA dairy goats compared with the control. SARA increased the plasma LPS ( P < 0.001), D-lactic acid contents ( P = 0.025) and DAO activity ( P = 0.003). Increased gene and protein expression of claudin-1 and occludin ( P < 0.05) were observed in colonic epithelium of SARA goats. Conclusion: Overall, the data of present study demonstrate that SARA can impair the barrier function of the colonic epithelium in dairy goats, which is associated with severe epithelial structural damage and increased permeability and changes in the expression of TJ proteins.
Progressive Proximal-to-Distal Reduction in Expression of the Tight Junction Complex in Colonic Epithelium of Virally-Suppressed HIV+ Individuals