Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice.

Mammalian siderophores are believed to play a critical role in maintaining iron homeostasis. However, the properties and functions of mammalian siderophores have not been fully clarified. In this study, we have employed Chrome Azurol S (CAS) assay which is a well-established method for bacterial siderophores study, to detect and quantify mammalian siderophores in urine samples. Our study demonstrates that siderophores in urine can be altered by diet, gut microbiota and inflammation. C57BL/6 mice, fed on plant-based chow diets which contain numerous phytochemicals, have more siderophores in the urine compared to those fed on purified diets. Urinary siderophores were up-regulated in iron overload conditions, but not altered by other tested nutrients status. Further, germ-free mice displayed 50% reduced urinary siderophores, in comparison to conventional mice, indicating microbiota biotransformation is critical in generating or stimulating host metabolism to create more siderophores. Altered urinary siderophores levels during inflammation suggest that host health conditions influence systemic siderophores level. This is the first report to measure urinary siderophores as a whole, describing how siderophores levels are modulated under different physiological conditions. We believe that our study opens up a new field in mammalian siderophores research and the technique we used in a novel manner has the potential to be applied to clinical purpose.

ß-carotene-producing bacteria residing in the intestine provide vitamin A to mouse tissues in vivo.

Vitamin A deficiency (VAD) is an overwhelming public health problem that affects hundreds of millions of people worldwide. A definitive solution to VAD has yet to be identified. Because it is an essential nutrient, vitamin A or its carotenoid precursor ß-carotene can only be obtained from food or supplements. In this study, we wanted to establish whether ß-carotene produced in the mouse intestine by bacteria synthesizing the provitamin A carotenoid could be delivered to various tissues within the body. To achieve this, we took advantage of the Escherichia coli MG1655*, an intestine-adapted spontaneous mutant of E. coli MG1655, and the plasmid pAC-BETA, containing the genes coding for the 4 key enzymes of the ß-carotene biosynthetic pathway (geranylgeranyl pyrophosphate synthase, phytoene synthase, phytoene desaturase, and lycopene cyclase) from Erwinia herbicola. We engineered the E. coli MG1655* to produce ß-carotene during transformation with pAC-BETA (MG1655*-ßC) and gavaged wild-type and knockout mice for the enzyme ß-carotene 15,15'-oxygenase with this recombinant strain. Various regimens of bacteria administration were tested (single vs. multiple and low vs. high doses). ß-Carotene concentration was measured by HPLC in mouse serum, liver, intestine, and feces. Enumeration of MG1655*-ßC cells in the feces was performed to assess efficiency of intestinal colonization. We demonstrated in vivo that probiotic bacteria could be used to deliver vitamin A to the tissues of a mammalian host. These results have the potential to pave the road for future investigations aimed at identifying alternative, novel approaches to treat VAD.

Vitamin A deficiency is associated with gastrointestinal and respiratory morbidity in school-age children.

Infection is an important cause of morbidity throughout childhood. Poor micronutrient status is a risk factor for infection-related morbidity in young children, but it is not clear whether these associations persist during school-age years. We examined the relation between blood concentrations of micronutrient status biomarkers and risk of gastrointestinal and respiratory morbidity in a prospective study of 2774 children aged 5-12 y from public schools in Bogotá, Colombia. Retinol, zinc, ferritin, mean corpuscular volume, hemoglobin, erythrocyte folate, and vitamin B-12 concentrations were measured in blood at enrollment into the cohort. Children were followed for 1 academic year for incidence of morbidity, including diarrhea with vomiting, cough with fever, earache or ear discharge with fever, and doctor visits. Compared with adequate vitamin A status (≥30.0 µg/dL), vitamin A deficiency (<10.0 µg/dL) was associated with increased risk of diarrhea with vomiting [unadjusted incidence rate ratio (IRR): 2.17; 95% CI: 0.95, 4.96; P-trend = 0.03] and cough with fever (unadjusted IRR: 2.36; 95% CI: 1.30, 4.31; P-trend = 0.05). After adjustment for several sociodemographic characteristics and hemoglobin concentrations, every 10 µg/dL plasma retinol was associated with 18% fewer days of diarrhea with vomiting (P < 0.001), 10% fewer days of cough with fever (P < 0.001), and 6% fewer doctor visits (P = 0.01). Every 1 g/dL of hemoglobin was related to 17% fewer days with ear infection symptoms (P < 0.001) and 5% fewer doctor visits (P = 0.009) after controlling for sociodemographic factors and retinol concentrations. Zinc, ferritin, mean corpuscular volume, erythrocyte folate, and vitamin B-12 status were not associated with morbidity or doctor visits. Vitamin A and hemoglobin concentrations were inversely related to rates of morbidity in school-age children. Whether vitamin A supplementation reduces the risk or severity of infection in children over 5 y of age needs to be determined.

Impact of Giardia intestinalis on vitamin a status in schoolchildren from northwest Mexico.

We conducted a cross-sectional study in northwest Mexico in order to investigate the association between giardiasis and serum vitamin A in 40 Giardia-infected and 70 Giardia-free schoolchildren who were covered by a regional school breakfast program. There were no significant differences in age, Z-scores for nutritional indices of height for age, weight for age, or weight for height, socioeconomic conditions (employment and education of the parents, household conditions, sanitation facilities, type of drinking water, and family income), and mean daily intakes of vitamin A in the Giardia-free (899 +/- 887 microg) and the Giardia-infected (711 +/- 433 microg) groups. A higher concentration of serum retinol was found in the Giardia-free group than in the Giardia-infected group (0.75 micromol/L versus 0.61 micromol/L, respectively; p < 0.0001). Giardia-infected children were more likely to be vitamin A-deficient than the Giardia-free children (OR = 3.2; 95% CI = 1.2-8.5). Although 95% of the children met the daily-recommended intakes of vitamin A, half of them showed subclinical vitamin A deficiency. It is recognized that vitamin A deficiency is multifactorial and giardiasis was a factor significantly associated with this deficiency in this study. Mexican program developers and policymakers should be aware about the distinction between dietary deficiencies and deficiency diseases when current national program strategies for parasitic control and vitamin A supplementation are redesigned.