Forchielli Maria Luisa, Walker W Allan
Department of Pediatrics, University of Bologna, Italy.
Br J Nutr. 2005 Apr;93 Suppl 1:S41-8. doi: 10.1079/bjn20041356.
The newborn infant leaves a germ-free intrauterine environment to enter a contaminated extrauterine world and must have adequate intestinal defences to prevent the expression of clinical gastrointestinal disease states. Although the intestinal mucosal immune system is fully developed after a full-term birth, the actual protective function of the gut requires the microbial stimulation of initial bacterial colonization. Breast milk contains prebiotic oligosaccharides, like inulin-type fructans, which are not digested in the small intestine but enter the colon as intact large carbohydrates that are then fermented by the resident bacteria to produce SCFA. The nature of this fermentation and the consequent pH of the intestinal contents dictate proliferation of specific resident bacteria. For example, breast milk-fed infants with prebiotics present in breast milk produce an increased proliferation of bifidobacteria and lactobacilli (probiotics), whereas formula-fed infants produce more enterococci and enterobacteria. Probiotics, stimulated by prebiotic fermentation, are important to the development and sustainment of intestinal defences. For example, probiotics can stimulate the synthesis and secretion of polymeric IgA, the antibody that coats and protects mucosal surfaces against harmful bacterial invasion. In addition, appropriate colonization with probiotics helps to produce a balanced T helper cell response (Th1=Th2=Th3/Tr1) and prevent an imbalance (Th1>Th2 or Th2>Th1) contributing in part to clinical disease (Th2 imbalance contributes to atopic disease and Th1 imbalance contributes to Crohn's disease and Helicobacter pylori-induced gastritis). Furthermore, a series of pattern recognition receptors, toll-like receptors on gut lymphoid and epithelial cells that interact with bacterial molecular patterns (e.g. endotoxin (lipopolysaccharide), flagellin, etc.), help modulate intestinal innate immunity and an appropriate adaptive immune response. Animal and clinical studies have shown that inulin-type fructans will stimulate an increase in probiotics (commensal bacteria) and these bacteria have been shown to modulate the development and persistence of appropriate mucosal immune responses. However, additional studies are needed to show that prebiotics can directly or indirectly stimulate intestinal host defences. If this can be demonstrated, then prebiotics can be used as a dietary supplement to stimulate a balanced and an appropriately effective mucosal immune system in newborns and infants.
新生婴儿离开无菌的子宫内环境，进入受污染的子宫外世界，必须具备足够的肠道防御能力，以防止出现临床胃肠道疾病状态。虽然足月出生后肠道黏膜免疫系统已完全发育，但肠道的实际保护功能需要初始细菌定植的微生物刺激。母乳中含有益生元低聚糖，如菊粉型果聚糖，它们在小肠中不被消化，而是以完整的大分子碳水化合物形式进入结肠，然后由常驻细菌发酵产生短链脂肪酸。这种发酵的性质以及肠道内容物的后续pH值决定了特定常驻细菌的增殖。例如，母乳中含有益生元的母乳喂养婴儿，双歧杆菌和乳酸菌（益生菌）的增殖增加，而配方奶喂养的婴儿则产生更多肠球菌和肠杆菌。益生元发酵刺激产生的益生菌对肠道防御的发育和维持很重要。例如，益生菌可以刺激聚合免疫球蛋白A的合成和分泌，这种抗体覆盖并保护黏膜表面免受有害细菌的侵袭。此外，适当的益生菌定植有助于产生平衡的辅助性T细胞反应（Th1 = Th2 = Th3/Tr1），并防止失衡（Th1>Th2或Th2>Th1），这在一定程度上导致临床疾病（Th2失衡导致过敏性疾病，Th1失衡导致克罗恩病和幽门螺杆菌引起的胃炎）。此外，一系列模式识别受体，即肠道淋巴和上皮细胞上与细菌分子模式（如内毒素（脂多糖）、鞭毛蛋白等）相互作用的Toll样受体，有助于调节肠道固有免疫和适当的适应性免疫反应。动物和临床研究表明，菊粉型果聚糖会刺激益生菌（共生细菌）增加，并且这些细菌已被证明可调节适当的黏膜免疫反应的发育和持续存在。然而，需要更多研究来证明益生元可以直接或间接刺激肠道宿主防御。如果能够证明这一点，那么益生元可以用作膳食补充剂，以刺激新生儿和婴儿体内平衡且有效的黏膜免疫系统。
