Abbas Munawar, Hayirli Zeynep, Drakesmith Hal, Andrews Simon C, Lewis Marie C
Food and Nutritional Sciences, University of Reading, Reading, United Kingdom.
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Front Nutr. 2022 Oct 4;9:927754. doi: 10.3389/fnut.2022.927754. eCollection 2022.
Iron deficiency is the most prevalent human micronutrient deficiency, disrupting the physiological development of millions of infants and children. Oral iron supplementation is used to address iron-deficiency anemia and reduce associated stunting but can promote infection risk since restriction of iron availability serves as an innate immune mechanism against invading pathogens. Raised iron availability is associated with an increase in enteric pathogens, especially Enterobacteriaceae species, accompanied by reductions in beneficial bacteria such as Bifidobacteria and lactobacilli and may skew the pattern of gut microbiota development. Since the gut microbiota is the primary driver of immune development, deviations from normal patterns of bacterial succession in early life can have long-term implications for immune functionality. There is a paucity of knowledge regarding how both iron deficiency and luminal iron availability affect gut microbiota development, or the subsequent impact on immunity, which are likely to be contributors to the increased risk of infection. Piglets are naturally iron deficient. This is largely due to their low iron endowments at birth (primarily due to large litter sizes), and their rapid growth combined with the low iron levels in sow milk. Thus, piglets consistently become iron deficient within days of birth which rapidly progresses to anemia in the absence of iron supplementation. Moreover, like humans, pigs are omnivorous and share many characteristics of human gut physiology, microbiota and immunity. In addition, their precocial nature permits early maternal separation, individual housing, and tight control of nutritional intake. Here, we highlight the advantages of piglets as valuable and highly relevant models for human infants in promoting understanding of how early iron status impacts physiological development. We also indicate how piglets offer potential to unravel the complexities of microbiota-immune responses during iron deficiency and in response to iron supplementation, and the link between these and increased risk of infectious disease.
缺铁是最普遍的人类微量营养素缺乏症，扰乱了数百万婴幼儿的生理发育。口服铁补充剂用于治疗缺铁性贫血并减少相关的发育迟缓，但可能会增加感染风险，因为限制铁的可利用性是抵御入侵病原体的一种先天免疫机制。铁可利用性的提高与肠道病原体尤其是肠杆菌科细菌的增加有关，同时伴随着双歧杆菌和乳酸菌等有益菌的减少，并且可能会改变肠道微生物群的发育模式。由于肠道微生物群是免疫发育的主要驱动因素，生命早期细菌演替的正常模式出现偏差可能会对免疫功能产生长期影响。关于缺铁和肠腔内铁的可利用性如何影响肠道微生物群的发育，以及随后对免疫的影响，我们所知甚少，而这些因素很可能是感染风险增加的原因。仔猪天生缺铁。这主要是由于它们出生时铁储备低（主要是因为产仔数多），以及它们生长迅速，同时母乳中铁含量低。因此，仔猪在出生后几天内就会持续缺铁，在不补充铁的情况下会迅速发展为贫血。此外，与人类一样，猪是杂食动物，具有许多与人类肠道生理、微生物群和免疫相关的特征。此外，它们早熟的特性允许早期与母体分离、单独饲养以及严格控制营养摄入。在此，我们强调仔猪作为有价值且高度相关的人类婴儿模型，在促进理解早期铁状态如何影响生理发育方面的优势。我们还指出仔猪如何有潜力揭示缺铁期间以及对铁补充剂作出反应时微生物群 - 免疫反应的复杂性，以及这些与传染病风险增加之间的联系。
