Fortificación con hierro de cereales infantilesbiodisponibilidad, expresión génica de transportadores y cambios en la microbiota intestinal

Abstract

Iron is an essential element for life, being fundamental for the optimal mental, motor and behavioural development of human beings. It is present in all cells of the body and is essential for many physiological processes, from oxygen transport and mitochondrial oxidation to dopamine and DNA synthesis. From a nutritional perspective, their lack in the diet results in ferropenia (depletion of iron reserves and circulating iron) and iron deficiency anaemia (affecting hematopoiesis). Anemia is a global public health problem that affects more than 1.6 billion people, including 47 % of pre-school children (0-5 years). With the present Doctoral Thesis, we have tried to study the bioavailability in vitro and in vivo, using different methodologies, of four iron salts that are used as fortifiers in children's cereals: Ferrous sulphate heptahydrate (FSH), Ferrous fumarate (FF), Micronized and encapsulated ferric pyrophosphate (MDFP) and Electrolytic iron (EI). In study 1, the main objective was to analyze the uptake and transport, as well as the possible differences in gene expression and location of iron transporters in the Caco-2 cell line, comparing the fortifiers Ferrous sulphate heptahydrate, Ferrous fumarate, Micronized and encapsulated ferric pyrophosphate and Electrolytic iron. The results and conclusions showed that the most available source of iron in all the parameters indicating mineral availability was FSH, followed by MDPF and FF, with EI being the source of iron with the lowest availability. In addition, most genes involved in iron absorption from the intestinal lumen were similarly expressed in all treatments, although MDFP increased gene expression of iron transporters related to iron absorption at the intestinal level, and FSH induced the highest absorption and accumulation of iron in the intestinal cell in the form of ferritin. To contrast the results of study 1 (in vitro), study 2 (in vivo) was designed with an animal model (weaned piglets), to evaluate the bioavailability of different forms of iron in anemic pigs by means of a depletion/replication test, and its possible pro-inflammatory. In addition, taxonomic modifications in the intestinal microbiota of these piglets due to diet fortification with the different forms of iron were analyzed and microbial metabolism was studied. To compare the status of the piglets, we randomized the animals into 6 study groups, 24 piglets were fed the different iron salts, while 6 of them were fed an un-fortified base feed (Control -). Furthermore, 6 non-anemic animals were fed FSH-fortified base feed (Control +). After treating the piglets with the different iron salts for 21 days, all groups showed significant improvements in the hematological indices as well as a recovery of the anemic status compared to the Control -. At the end of the experiment, FF and FSH piglets showed higher values than EI and MDFP in most of the variables analyzed. The bioavailability of the different iron salts was higher in the FF and MDFP group with respect to the FSH, showing the EI the worst results. As for the changes observed in the intestinal microbiota, the most similar to the non-anemic group appears after fortification with FF or MDFP, being significantly different from the non-anemic or EI treated piglets. Study 3 was conducted using the Human Intestinal Microbial Ecosystem Simulator (SHIME) inoculated with fecal samples from healthy infants. Taking as a reference the results obtained in studies 1 and 2, we evaluated the effect of a child cereal fortified with three types of iron sources: FSH, MDFP and FF, on the activity of luminal intestinal microbiota in vitro. The modifications produced by these fortifiers in the intestinal microbiota and in the microbial metabolism were analyzed. The results and conclusions of this study show that treatment with the three iron salts (FSH, MDFP and FF) increased the concentration of propionate. In addition, butyrate production gradually decreased during the 3 weeks of treatment in both the proximal and distal colon. With regard to the microbiota studied, it should be noted that no statistically significant differences were found between the 3 iron salts for the microbial groups analyzed (Akkermansia muciniphila, Bifidobacteria, Lactobacilli, phylum Bacteroidetes and phylum Firmicutes). However, there is a superior colonization of beneficial bacteria with MDFP.