Protection of the Neonate by the Innate Immune System of Developing Gut and of Human Milk

Abstract

ABSTRACT:The neonatal adaptive immune system, relatively naïve to foreign antigens, requires synergy with the innate immune system to protect the intestine. Goblet cells provide mucins, Paneth cells produce antimicrobial peptides, and dendritic cells (DCs) present luminal antigens. Intracellular signaling by Toll-like receptors (TLRs) elicits chemokines and cytokines that modulate inflammation. Enteric neurons and lymphocytes provide paracrine and endocrine signaling. However, full protection requires human milk. Breast-feeding reduces enteric infection and may reduce chronic disease in later life. Although human milk contains significant secretory immunoglobulin A (sIgA), most of its protective factors are constitutively expressed. Multifunctional milk components are nutrients whose partial digestion products inhibit pathogens. Cytokines, cytokine receptors, TLR agonists and antagonists, hormones, antiinflammatory agents, and nucleotides in milk modulate inflammation. Human milk is rich in glycans (complex carbohydrates): As prebiotics, indigestible glycans stimulate colonization by probiotic organisms, modulating mucosal immunity and protecting against pathogens. Through structural homology to intestinal cell surface receptors, glycans inhibit pathogen binding, the essential first step of pathogenesis. Bioactive milk components comprise an innate immune system of human milk whereby the mother protects her nursing infant. Interactions between human milk glycans, intestinal microflora, and intestinal mucosa surface glycans underlie ontogeny of innate mucosal immunity, pathobiology of enteric infection, and inflammatory bowel diseases. (Pediatr Res 61: 2-8, 2007)

Intestinal gene expression profiles of piglets benefit from maternal supplementation with a yeast mannan-rich fraction during gestation and lactation

“…MRF (n = 40) and control (n = 22). Graugnard, Samuel, Xiao, Spangler and Brennan (Simmen et al, 1990;Hanson et al, 2001;Blum, 2006;Newburg and Walker, 2007). Our study reported a greater percentage of protein and total solids less fat in the milk of the group supplemented with MRF.…”

Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial

“…Many efforts have been made to make the composition of formula (e.g. proteins and fats) as close as possible to breast milk (6,7) .Human milk oligosaccharides, after lactose and lipids, represent the third largest solid component in breast milk, and contribute to immune modulation and infection prevention (8,9) . They exert prebiotic function by acting as soluble analogues to epithelial receptors for specific microbes, and this prevents their adhesion to the intestinal wall (10,11) .…”

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant

“…In addition to transfer of immunoglobulin G to the fetus through the placenta, breastfeeding constitutes an important immunological support that the mammalian mother can provide to her relatively immunocompromised offspring against infections during the first months of life (2)(3)(4)(5)(6). The immune system in human milk includes secretory immunoglobulin A (sIgA), immunoglobulin G, free fatty acids, monoglycerides, proteins such as lactoferrin, lactalbumin, glycans, nonabsorbed oligosaccharides, exosomes, immunomodulators such as cytokines, nucleic acids, antioxidants, and immune cells such as macrophages, neutrophils, and lymphocytes (1,4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

“…The immune system in human milk includes secretory immunoglobulin A (sIgA), immunoglobulin G, free fatty acids, monoglycerides, proteins such as lactoferrin, lactalbumin, glycans, nonabsorbed oligosaccharides, exosomes, immunomodulators such as cytokines, nucleic acids, antioxidants, and immune cells such as macrophages, neutrophils, and lymphocytes (1,4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). All these immunologic milk constituents interact together and with the newborn's gut directly or indirectly (e.g., by changing the gut flora) to increase immunity against infection, and probably also contribute to the maturation and efficiency of the newborn immune system (5,6).…”