Albertine Donker

Chapter 2 66 children both in low-middle income and high-income countries, 60,61 rendering them more vulnerable to infections and possibly also to a suboptimal response to vaccinations. 115 Interestingly, high neonatal iron blood count was associated with an increased risk of the development of diabetes mellitus type I before the age of 16 years, 116 suggesting that IO in early life may also negatively affect T cell count and function, setting a trend to auto-immunity. Moreover, high iron body content makes the human body an attractive host for iron-dependent pathogens. 4 Clinical evidence exists that iron restriction is protective against malaria, respiratory tract infections and diarrrhoea in low-income countries. 27,117,118 Iron influences the development of the gut microbiota Growing evidence emphasises the important implications of the gut microbiota for human health and disease. 106 The way the infant interacts with intestinal microbes programmes immune and metabolic pathways that persist into adulthood. 106 Inflammatory bowel disease, functional gastro-intestinal disorders, allergies, obesity and liver disease are all thought to be associated with an imbalance or alteration in the composition and/or the function of the intestinal microbiota during early life. 119 Initiation of the microbial colonisation of the intestine may start in utero from the mother to the fetus, challenging the idea of a sterile colon at birth. 120 However, the development of the gut microbiota primarily occurs after birth, during infancy. Environmental factors as gestational age, mode of delivery, type of feeding (breast- versus formula feeding), exposure to antibiotics and to proton pump inhibitors all influence the variability of microbiome development in children. 106,119 Iron also influences the gut microbiotica. Accumulating preclinical and clinical evidence indicates that unabsorbed nutritional iron enters the colon and may have unfavorable effects on the intestinal microbiotica-host interface. 38,121 Pathogenic species as Enterobacteriaceae can take advantage of an iron-rich intestinal environment at the expense of beneficial species as Bifidobacteria and Lactobacilli species, important for the production of short chain fatty-acids and for the integrity of the gut barrier, resulting in an unfavorable shift towards an adverse microbial profile. 38 Especially preterm infants are at risk for the occurrence of this dysbiosis. 122 Notably, nutritional guidelines that balance the possible benefits or iron supplementation against the risk of perturbation of the gut microbiota, are lacking until now. 33,122