Responses of the gut microbiota to supplementary iron: a survey at the host-microbial interface

Contains fulltext : 132635.pdf (publisher's version ) (Open Access)Iron is a highly abundant metal on earth and is vital for virtually all organisms, including most bacterial species. Nonetheless, iron deficiency is the most prevalent human nutrition disorder worldwide, which can generally be treated by oral iron administration. However, oral iron administration in infection endemic regions is associated with an increased susceptibility of children to infections. The aim of this thesis was to investigate the impact of oral iron administration at the intestinal epithelial interface on i) the pathogenicity of intestinal pathogens, ii) the gut microbiota composition, iii) gut microbial metabolism, and iv) host responses. This thesis exemplifies that oral administration can increase the abundance of intestinal pathogens and may increase their pathogenicity, while it can decrease the abundance of beneficial gut microbes. Furthermore, it may also decrease host intestinal defenses (i.e. via: iron-induced oxidative damage to the gut wall, increased production of toxic microbial metabolites affecting the gut wall, or a decreased host innate defense) at the same time. This undesired combination may provide intestinal pathogens with increased opportunities to evade the host defense during oral iron therapy. Together this strengthens the idea that oral iron administration programs in developing countries with high infection pressure need to be set up with the highest amount of care, and should be accompanied with close health monitoring until the remaining questions about the actual effect of iron at the intestinal host-microbiota interface have been unraveled. Future research should also be directed at finding iron formulations that minimize the negative impact on the gut microbiome. This thesis exposes health problems and potential threats with regarding to oral iron administration and it increases the understanding of iron-driven alterations of host-pathogen interactions, which is indispensible in the design of safe iron formulations.Radboud Universiteit Nijmegen, 16 december 2014Promotor : Swinkels, D.W. Co-promotor : Tjalsma, H