Cécile Perrier

A mixture of milk and vegetable lipids in infant formula changes gut digestion, mucosal immunity and microbiota composition in neonatal piglets

PurposeAlthough composition of infant formula has been significantly improved during the last decade, major differences with the composition and structure of breast milk still remain and might affect nutrient digestion and gut biology. We hypothesized that the incorporation of dairy fat in infant formulas could modify their physiological impacts by making their composition closer to that of human milk. The effect of milk fat and milk fat globule membrane (MFGM) fragments in infant formulas on gut digestion, mucosal immunity and microbiota composition was evaluated.MethodsThree formulas containing either (1) vegetable lipids stabilized only by proteins (V-P), (2) vegetable lipids stabilized by a mixture of proteins and MFGM fragments (V-M) and (3) a mixture of milk and vegetable lipids stabilized by a mixture of proteins and MFGM fragments (M-M) were automatically distributed to 42 newborn piglets until slaughter at postnatal day (PND) 7 or 28, and compared to a fourth group of sow’s suckling piglets (SM) used as a breast-fed reference.ResultsAt both PND, casein and β-lactoglobulin digestion was reduced in M-M proximal jejunum and ileum contents compared to V-P and V-M ones leading to more numerous β-Cn peptides in M-M contents. The IFNγ cytokine secretion of ConA-stimulated MLN cells from M-M piglets tended to be higher than in V-P ones at PND 7 and PND 28 and was closer to that of SM piglets. No dietary treatment effect was observed on IL-10 MLN cell secretion. Changes in faecal microbiota in M-M piglets resulted in an increase in Proteobacteria and Bacteroidetes and a decrease in Firmicutes phyla compared to V-P ones. M-M piglets showed higher abundances of Parabacteroides, Escherichia/Shigella and Klebsiella genus.ConclusionsThe incorporation of both milk fat and MFGM fragments in infant formula modifies protein digestion, the dynamic of the immune system maturation and the faecal microbiota composition.

A high-protein formula increases colonic peptide transporter 1 activity during neonatal life in low-birth-weight piglets and disturbs barrier function later in life.

Dietary peptides are absorbed along the intestine through peptide transporter 1 (PepT-1) which is highly responsive to dietary protein level. PepT-1 is also involved in gut homeostasis, both initiating and resolving inflammation. Low-birth-weight (LBW) neonates are routinely fed a high-protein (HP) formula to enhance growth. However, the influence of this nutritional practice on PepT-1 activity is unknown. Intestinal PepT-1 activity was compared in normal-birth-weight (NBW) and LBW piglets. The effect of HP v. normal-protein (NP) formula feeding on PepT-1 activity and gut homeostasis in LBW piglets was evaluated, during the neonatal period and in adulthood. Flux of cephalexin (CFX) across the tissue mounted in Ussing chambers was used as an indicator of PepT-1 activity. CFX flux was greater in the ileum, but not jejunum or colon, of LBW than NBW piglets during the neonatal period. When LBW piglets were formula-fed, the HP formula increased colonic CFX during the 1st week of life. Later in life, intestinal CFX fluxes and barrier function were similar whether LBW pigs had been fed NP or HP formula. However, colonic permeability of HP- but not NP-fed pigs increased when luminal pH was brought to 6·0. The formyl peptide N-formyl methionyl-leucyl-phenylalanine conferred colonic barrier protection in HP-fed piglets. Heat shock protein 27 levels in the colonic mucosa of HP-fed LBW pigs correlated with the magnitude of response to the acidic challenge. In conclusion, feeding a HP formula enhanced colonic PepT-1 activity in LBW pig neonates and increased sensitivity of the colon to luminal stress in adulthood.

Maternal 18:3n-3 favors piglet intestinal passage of LPS and promotes intestinal anti-inflammatory response to this bacterial ligand.

We recently observed that maternal 18:3n-3 increases piglet jejunal permeability. We hypothesized that this would favor intestinal lipopolysaccharide (LPS) passage and alter gut immune system education toward this bacterial ligand. Sows were fed 18:3n-3 or 18:2n-6 diets throughout gestation and lactation. In each litter, two piglets were given oral Gram-negative spectrum antibiotic from post-natal day (PND) 14 to 28. All piglets were weaned on a regular diet at PND28. 18:3n-3 piglets exhibited greater jejunal permeability to FITC-LPS at PND28. Levels of 18:3n-3 but neither 20:5n-3 nor 20:4n-6 were greater in mesenteric lymph nodes (MLN) of 18:3n-3 piglets. Jejunal explant or MLN cell cytokine responses to LPS were not influenced by the maternal diet. Antibiotic increased jejunal permeability to FITC-LPS and lowered the level of 20:5n-3 in MLN, irrespective of the maternal diet. At PND52, no long-lasting effect of the maternal diet or antibiotic treatment on jejunal permeability was noticed. 18:3n-3 and 20:4n-6 levels were greater and lower, respectively, in MLN of 18:3n-3 compared to 18:2n-6 piglets. IL-10 production by MLN cells in response to LPS was greater in the 18:3n-3 group, irrespective of the neonatal antibiotic treatment. IL-8 secretion by jejunal explants in response to LPS was lower in antibiotic-treated 18:3n-3 compared to 18:2n-6 piglets. Finally, proportion of MHC class II(+) antigen-presenting cells was greater in 18:3n-3 than 18:2n-6 MLN cells. In conclusion, maternal 18:3n-3 directs the intestinal immune response to LPS toward an anti-inflammatory profile beyond the breastfeeding period; microbiota involvement seems dependent of the immune cells considered.

Alterations in ileal and colonic permeability by chronic intake of high-lipid diets enriched with omega 3, omega 6 or saturated fat

Gut permeability is a key function often incriminated in the development of local and systemic insammation. Chronic consumption ofhigh-fat diets leads to obesity and insammation. Data in mice revealed a causal increase in intestinal permeability to bacterial lipopoly-saccharide (LPS) that may be responsible for adipose tissue development and insammation