Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats

Objectives: Psychological stress during the neonatal period results in intestinal barrier dysfunction and growth alterations later in life. We aimed to restore impaired barrier function and growth rate by a nutritional intervention. Methods: Male rat pups (n = 84) were assigned to 1 of 2 rearing conditions from postnatal day (PND) 2 to PND14: S, separated 3 h/d from their mothers, or H, 15 min/d handled controls. From PND15 to PND35, rats received a control diet or a similar diet adapted to contain arachidonic and docosahexaenoic acids, galacto- and fructo-oligosaccharides and Lactobacillus para-casei NCC2461. Results: Maternal separation had only a minor impact on the measured gut barrier parameters at PND15, whereas it severely affected them at PND35. At this age, intestinal permeability to macromolecules was higher, mucin content in small intestinal tissues was lower and microbiota composition was altered in S compared with H animals. Feeding the adapted diet normalized the intestinal permeability, although it did not restore intestinal mucin content or microbiota. In addition, the adapted diet improved the growth rate recovery of the S animals after weaning and resulted in increased villus length in small intestine. Conclusion: Our results suggest that an adapted diet containing specific long-chain polyunsaturated fatty acids, prebiotics and probiotics can revert the negative imprinting of neonatal stress on both intestinal barrier function and growth.