Biochemistry Post-Graduate Program, Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil.
Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, 1205 Geneva, Switzerland.
Nutrients. 2022 Jul 17;14(14):2923. doi: 10.3390/nu14142923.
Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many "constitutive" elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophin production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). In this context, Lf can provide nutritional support for brain development and cognition and prevent the origin of neuropsychiatric diseases later in life. In this narrative review, we consider the role of certain nutrients during neurodevelopment linking to the latest research on lactoferrin with respect to neonatology. We also discuss new evidence indicating that early neuroprotective pathways modulated by Lf could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes.
早期不良胎儿环境会显著干扰中枢神经系统 (CNS) 的发育，随后改变大脑成熟度。营养状况是发育过程中需要考虑的主要变量，越来越多的证据表明，新生儿和早产儿的大脑生长受损与成年后的神经和精神疾病有关。母乳喂养是健康新生儿发育的主要组成部分之一，因为母乳中含有许多“构成”成分。哺乳期母亲摄入特定营养物质可能会改变乳汁成分，从而影响新生儿的营养状况，并可能影响大脑发育。乳铁蛋白 (Lf) 是初乳中存在的主要蛋白质，也是人乳中的主要蛋白质，在新生儿发育过程中的母乳喂养益处中发挥着重要作用。已经证明 Lf 具有抗菌和抗炎特性，并且有可能降低败血症和坏死性小肠结肠炎 (NEC) 的发病率，这在早产儿中尤为常见。Lf 的抗炎作用可以通过减少促炎因子的释放和抑制过早的宫颈成熟（也与共生微生物组异常有关）来减少与出生相关的病理，从而有助于破坏大脑发育。临床前证据表明，Lf 可保护发育中的大脑免受神经元损伤，增强大脑连接和神经营养因子的产生，并减少围产期炎症挑战、宫内生长受限 (IUGR) 和新生儿缺氧缺血 (HI) 模型中的炎症。在这种情况下，Lf 可以为大脑发育和认知提供营养支持，并预防神经精神疾病在以后生活中的发生。在这篇叙述性综述中，我们考虑了神经发育过程中某些营养物质的作用，并结合最新的乳铁蛋白在新生儿学方面的研究进行了讨论。我们还讨论了新的证据，表明 Lf 调节的早期神经保护途径可以通过抗炎和免疫调节过程预防神经退行性变。
