Search

Intrauterine growth restriction (IUGR) can affect the structure and function of the intestinal barrier and increase digestive disease risk in adulthood. Using the rat model of maternal dietary protein restriction (8% vs. 20%), we found that the colon of IUGR offspring displayed decreased mRNA expression of epithelial barrier proteins MUC2 and occludin during development. This was associated with increased mRNA expression of endoplasmic reticulum (ER) stress marker XBP1s and increased colonic permeability measured in Ussing chambers. We hypothesized that ER stress contributes to colonic barrier alterations and that perinatal supplementation of dams with ER stress modulators, phenylbutyrate and glutamine (PG) could prevent these defects in IUGR offspring. We first demonstrated that ER stress induction by tunicamycin or thapsigargin increased the permeability of rat colonic tissues mounted in Ussing chamber and that PG treatment prevented this effect. Therefore, we supplemented the diet of control and IUGR dams with PG during gestation and lactation. Real-time polymerase chain reaction and histological analysis of colons from 120-day-old offspring revealed that perinatal PG treatment partially prevented the increased expression of ER stress markers but reversed the reduction of crypt depth and goblet cell number in IUGR rats. In dextran sodium sulfate-induced injury and recovery experiments, the colon of IUGR rats without perinatal PG treatment showed higher XBP1s mRNA levels and histological scores of inflammation than IUGR rats with perinatal PG treatment. In conclusion, these data suggest that perinatal supplementation with PG could alleviate ER stress and prevent epithelial barrier dysfunction in IUGR offspring. [ABSTRACT FROM AUTHOR]

To assess the impact of prebiotic supplementation during gestation and fetal and early neonatal life, gestating BALB/cj dam mice were fed either a control or a prebiotic (galacto-oligosaccharides–inulin, 9:1 ratio)-enriched diet throughout pregnancy and lactation, and allowed to nurse their pups until weaning. At the time of weaning, male offspring mice were separated from their mothers, weaned to the same solid diet as their dam and their growth was monitored until killed 48 d after weaning. Prebiotic treatment affected neither the body-weight gain nor the food intake of pregnant mice. In contrast, at the time of weaning, pups that had been nursed by prebiotic-fed dams had a higher body weight (11·0 (se 1·2) g) than pups born from control dams (9·8 (se 0·9) g). At 48 d after weaning, significantly higher values were observed for colon length and muscle mass in the offspring of prebiotic-fed dams (1·2 (se 0·1) cm/cm and 5·7 (se 1·8) mg/g, respectively), compared with control offspring (1·1 (se 0·1) cm/cm and 2·9 (se 0·9) mg/g, respectively), without any difference in spleen and stomach weight, or serum leptin concentration. The present preliminary study suggests that altering the fibre content of the maternal diet during both pregnancy and lactation enhances offspring growth, through an effect on intestinal and muscle mass rather than fat mass accretion. [ABSTRACT FROM PUBLISHER]