Piglet Growth Before Weaning has Long-Term Effects on Intestinal Barrier Function

Abstract Text: In mice, weaning stress increases intestinal permeability partly through a mechanism that involves TNF-α, intestinally-produced glucocorticoids, and myosin like chain kinase (MLCK). Recent evidence suggests that this interplay takes place predominantly in the colonic mucosa and has long-lasting effects on intestinal development and function. Interestingly, the impact of weaning-induced intestinal dysfunction is inversely correlated to age at weaning. However, little is known about the impact that pre-weaning growth has on post-weaning gut permeability and animal performance. The aim of this experiment was to investigate the effect of pre-weaning growth on intestinal permeability and underlying regulatory pathways. To this end, 18 piglets ((LW x LD) x Pietrain) were weighed and identified at birth. At weaning (21 d of age) piglets were divided into two groups (n = 9): fast growers (FG) or slow growers (SG) according to their growth rate from birth to weaning.  Thereafter, piglets were housed individually and fed ad libitum non-medicated pre-starter (21 - 35 d) and starter (35 - 56 d) feeds. Individual BW and feed intake were registered weekly. On day 56, plasma for cortisol determination and recovery of permeability markers (Co-EDTA and mannitol) was obtained 1 h after marker intragastric infusion. Immediately after, ascendant colon samples were harvested for measurement of cortisol, TNF-α and MLCK mRNA in colonic mucosa. Performance data were analyzed with a mixed-effect model with repeated measures in which pig was treated as random and treatment, week and its interaction were considered fixed effects. Pigs in the SG group had a lower pre-weaning growth rate (181 vs. 208 ± 13.1 g/d; P < 0.04) and BW at d 21 (6.0 vs. 6.3 ± 0.005 kg; P < 0.05) than FG counterparts. At d 56, plasma cortisol was not different between groups. However, the ratio Co/mannitol in plasma was higher in SG than FG (28.7 vs. 11.9 ± 13.0; P < 0.001). In addition, SG pigs had a higher concentration of cortisol (20.0 vs. 2.5 ± 2.7 ng/mg of protein; P < 0.001) and TNF-a (0.15 vs. 0.09 ± 0.01 ng/mg of protein; P < 0.001) in the colonic mucosa. Interestingly, abundance of MLCK mRNA in colon mucosa was 35% lower (P < 0.05) in FG compared with SG. In conclusion, pre-weaning growth rate has a long-lasting impact on gut permeability and the mechanism underlying this phenomenon appears to be regulated locally at the colon epithelium.

Keywords: permeability, stress, cortisol