Method for stimulating intestinal barrier integrity after non-natural birth

The present invention relates to methods for feeding and therapy infants delivered via caesarean section.

Infants have an immature intestine at birth. After birth, the neonatal gastro-intestinal tract undergoes rapid growth and maturation, including mucus formation and maturation and closing of tight junctions to allergens, toxins and pathogenic micro-organisms. In human milk several factors are present which improve gut maturation.

A permeable, immature intestinal barrier plays a role in the acquirement of intestinal inflammation, infections, diarrhea, and atopic diseases including food allergy. A properly maturing intestine, especially in combination with a healthy intestinal flora, results in a reduced incidence of infections, a strengthened immune system, a reduced incidence of food allergy and/or other atopic diseases, and/or a reduced incidence of diarrhea, constipation and/or intestinal inflammation.

Intestinal permeability decreases faster in breast-fed babies than in formula-fed infants. However, not always is breast-feeding realizable.

WO2004112509 describes a composition for inducing a pattern of intestinal barrier maturation similar to that observed with breast-feeding and able to improve intestinal barrier maturation, e.g. during neonatal stress.

WO2005122790 describes a method for stimulating barrier integrity in a mammal by administering to a mammal a composition comprising: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (ARA), and at least two distinct oligosaccharides.

EP1549158 describes infant formula compositions which comprise 3.2 mg/L to 15.4 mg/L of CMP; 1.8 mg/L to 11.0 mg/L of UMP; 1.8 mg/L to 8.0 mg/L of GMP; 0.1 mg/L to 2.2 mg/L of IMP; and 2.5 mg/L to 13.2 mg/L of AMP.

WO03043445 describes processed baby foods which are formulated with a) oils, b) nucleotides, c) oils and nucleotides.

Natren® produces the probiotic product Life Start® which is designed specifically for infants and suitable for infants delivered via caesarean section. Life Start® is made with Bifidobacterium infantis. Because the Life Start® product contains only one single Bifidobacteria species, the benefits for the infant will be very limited.

The present inventors have found that infants delivered via caesarean section have an intestinal flora which is different from the intestinal flora of infants born via the vaginal route. Particularly, infants born via caesarean section have a reduced rate of intestinal colonization by Bifidobacteria and have a less diverse Bifidobacterium intestinal flora regarding species than infants born via the vaginal route, particularly missing Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis and Bifidobacterium bifidum. It was further found that the intestinal flora of infants delivered via caesarean section have a lower content of Bifidobacteria compared to the intestinal flora of infants delivered vaginally. Additionally it was found that the intestinal flora of infants born via caesarean section has a high content of (undesirable) Escherichia coli 6 weeks after delivery.

A healthy and fully developed gastrointestinal flora has important physiological effects. One important aspect is that it reduces the occurrence of (gastrointestinal) infections. Because infants delivered via a caesarean section lack a healthy flora, preventing infection is particularly important for these infants. These infants are normally delivered in a hospital environment, which is a risk for pathogenic infection due to the occurrence of nosocomial bacteria. Additionally, the impaired development of a healthy intestinal flora results in faster colonization of pathogenic bacteria compared to a situation where the infants intestinal tract is inoculated by maternal bacteria originating from the mother\'s vaginal and fecal flora. In order to prevent bacterial translocation or translocation of bacterial (eno- or exo)toxins across the intestinal barrier of these (nosocomial) pathogens, it is of utmost importance to improve and/or accelerate intestinal maturation in caesarean section delivered infants. Improvement of the intestinal barrier maturation and/or barrier integrity in caesarean section delivered infants furthermore reduces the incidence of intestinal inflammation, food allergy and/or other atopic diseases.

The inventors have recognized that the barrier function of babies born via caesarean section is impaired and found that long-chain polyunsaturated fatty acids (LC-PUFA) and/or nucleotides improve the maturation and integrity of the intestinal barrier, and/or have an anti-inflammatory effect in babies delivered via caesarean section. LC-PUFA furthermore promote the adhesion of lactic acid producing bacteria to mucosal surfaces. Hence, the present invention concerns the use of compositions comprising LC-PUFA and/or nucleotide that particularly aim to a) decrease the incidence of infections by increasing intestinal barrier integrity and/or maturation, b) decrease the incidence of (food) allergy and/or atopic diseases by increasing intestinal barrier integrity and/or maturation, c) dampen or subdue intestinal inflammatory processes that otherwise would further increase intestinal barrier permeability, and/or d) improve the flora by increasing colonization of lactic acid producing bacteria to mucosal surfaces in infants delivered by caesarean section.

In a further aspect the present invention can be suitably brought to practice by incorporation of the present active ingredients in a nutritional composition. Such composition can be administered to the infant without posing a heavy burden on the infant delivered via caesarean section.

The present invention provides the use of a composition comprising (i) long chain polyunsaturated fatty acid (LC-PUFA); and/or (ii) at least one selected from the group consisting of (a) nucleotide and (b) nucleotide precursor selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and deoxyribose for the manufacture of a composition for administration to an infant delivered via caesarean section. In a further aspect the present method provides the use of a composition comprising (i) long chain polyunsaturated fatty acid (LC-PUFA); and/or (ii) at least one selected from the group consisting of (a) nucleotide and (b) nucleotide precursor selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and deoxyribose for the manufacture of a composition for i) treatment and/or prevention of disorders in infants delivered via caesarean section and/or ii) the stimulation of health in infants delivered via caesarean section.

The present invention also provides a method for feeding an infant delivered via caesarean section, said method comprising administering to said infant a composition comprising (i) long chain polyunsaturated fatty acid (LC-PUFA) anchor (ii) at least one selected from the group consisting of (a) nucleotide and (b) nucleotide precursor selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and deoxyribose.

A caesarean section (c-section) is a surgical procedure where an infant is delivered through an incision made in the mother\'s abdominal wall, and then through the wall of the uterus. A caesarean section is usually performed when it is safer for the mother or the infant than a vaginal delivery. Other times, a woman may choose to have a caesarean section rather than deliver her infant vaginally.