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Hemmerling J.,TU Munich | Hemmerling J.,Research Center for Nutrition and Food science | Heller K.,TU Munich | Heller K.,Research Center for Nutrition and Food science | And 9 more authors.
PLoS ONE | Year: 2014

Background: Chronic inflammatory disorders have been increasing in incidence over the past decades following geographical patterns of industrialization. Fetal exposure to maternal inflammation may alter organ functions and the offspring's disease risk. We studied the development of genetically-driven ileitis and colitis in response to maternal inflammation using mouse models. Methods: Disease susceptible (TnfΔARE/+ and IL10-/-) and disease-free (Tnf+/+ and IL10-/+) offspring were raised in inflamed and non-inflamed dams. Ileal, caecal and colonic pathology was evaluated in the offspring at 8 or 12 weeks of age. Ly6G-positive cells in inflamed sections from the distal ileum and distal colon were analysed by immunofluorescence microscopy. Gene expression of pro-inflammatory cytokines was measured in whole tissue specimens by quantitative PCR. Microarray analyses were performed on laser microdissected intestinal epithelium. Caecal bacterial communities were assessed by Illumina sequencing of 16S rRNA amplicons. Results: Disease severity, the number of infiltrated neutrophils as well as Tnf and Il12p40 mRNA expression were independent of maternal inflammation in the offspring of mouse models for ileitis (TnfΔARE/+) and colitis (IL10-/-). Although TNF-driven maternal inflammation regulated 2,174 (wild type) and 3,345 (Tnf ΔARE/+) genes in the fetal epithelium, prenatal gene expression patterns were completely overwritten after birth. In addition, co-housing experiments revealed no change in phylogenetic diversity of the offspring's caecal microbiota in response to maternal inflammation. This is independent of the offspring's genotype before and after the onset of tissue pathology. Conclusions: Disease risk and activity in mouse models of chronic ileitis and colitis was independent of the fetal exposure to maternal inflammation. Likewise, maternal inflammation did not alter the diversity and composition of offspring's caecal microbiota, clearly demonstrating that changes of the gene expression program in the fetal gut epithelium were not relevant for the development of chronic inflammatory disorders in the gut. © 2014 Hemmerling et al.


Schumann K.,Research Center for Nutrition and Food Science | Solomons N.W.,Center for Studies of Sensory Impairment | Orozco M.,Center for Studies of Sensory Impairment | Romero-Abal M.E.,Center for Studies of Sensory Impairment | Weiss G.,Innsbruck Medical University
Food and Nutrition Bulletin | Year: 2013

Background. The adverse interactions between iron supplements and malaria have driven the assessment of new therapeutic options for anemia prophylaxis in areas holoendemic for falciparum malaria. Objective. To determine the responses of circulating non-transferrin-bound iron (NTBI) and plasma iron to three different oral iron compounds-ferrous sulfate, sodium iron ethylenediaminetetraacetate (NaFeEDTA), and iron polymaltose (IPM)-in women with marginal iron stores. Methods. Serum samples from 10 Guatemalan women with marginal iron stores were collected every 90 minutes over a period of 270 minutes, after the individually randomized administration of 100 mg of iron from each of the three studied iron compounds or water alone. Serum iron concentration was quantified by the ferrozine method, and circulating NTBI concentration was determined with a fluorometric competitive binding assay. Kinetic responses and maximal cumulative changes in serum concentrations of iron and NTBI were compared between the four treatments. Comparison was made with data from the same protocol in iron-adequate men. Results. The serum iron and NTBI responses to ferrous sulfate were significantly greater than those to water and the other two iron compounds. Serum iron responses to IPM did not differ from those to water alone. Conclusions. The administration of the two "slowrelease" iron compounds, NaFeEDTA and IPM, resulted in a highly significant suppression of the appearance of NTBI in the circulation in the postsupplement period. These two bioavailable forms of iron supplement could represent a safe option for supplementation in malarial areas. The slope of the iron-NTBI relationship is steeper in men than in women. © 2013, The United Nations University.


Brunner S.,TU Munich | Schmid D.,TU Munich | Huttinger K.,TU Munich | Much D.,TU Munich | And 10 more authors.
Diabetic Medicine | Year: 2013

Aims: The intrauterine metabolic environment might have a programming effect on offspring body composition. We aimed to explore associations of maternal variables of glucose and lipid metabolism during pregnancy, as well as cord blood insulin, with infant growth and body composition up to 2 years post-partum. Methods: Data of pregnant women and their infants came from a randomized controlled trial designed to investigate the impact of nutritional fatty acids on adipose tissue development in the offspring. Of the 208 pregnant women enrolled, 118 infants were examined at 2 years. In the present analysis, maternal fasting plasma insulin, homeostasis model assessment of insulin resistance and serum triglycerides measured during pregnancy, as well as insulin in umbilical cord plasma, were related to infant growth and body composition assessed by skinfold thickness measurements and abdominal ultrasonography up to 2 years of age. Results: Maternal homeostasis model assessment of insulin resistance at the 32nd week of gestation was significantly inversely associated with infant lean body mass at birth, whereas the change in serum triglycerides during pregnancy was positively associated with ponderal index at 4 months, but not at later time points. Cord plasma insulin correlated positively with birthweight and neonatal fat mass and was inversely associated with body weight gain up to 2 years after multiple adjustments. Subsequent stratification by gender revealed that this relationship with weight gain was stronger, and significant only in girls. Conclusions: Cord blood insulin is inversely associated with subsequent infant weight gain up to 2 years and this seems to be more pronounced in girls. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.


Hemmerling J.,TU Munich | Hemmerling J.,Research Center for Nutrition and Food science | Jansen J.,Wageningen University | Muller M.,University of East Anglia | And 2 more authors.
Journal of Immunological Methods | Year: 2015

Laser microdissection (LMD) technology enables highly specific gene expression analyses of biologically relevant questions at cell- or tissue-specific resolution. Nevertheless, specific cell types are often limited in quantity (i.e. fetal tissue), making high quality RNA extraction and subsequent gene expression approaches via common reverse transcriptase-quantitative PCR (RT-q-PCR) challenging. In the case of fetal gut epithelia representing immune modulatory interphases gene expression analysis with common RT-q-PCR is limited to a few genes (<10). To circumvent these limitations we provide a workflow using laser microdissection of 1.5Mioμm2 dissected area of murine fetal intestinal epithelial cells (IEC) from fetal ileum and colon with subsequent RNA isolation, whole transcriptome preamplification (WTA) and gene expression analysis by microarray and quantitative PCR (qPCR). This workflow allows simultaneous analyses of global (microarrays) and targeted gene expression (qPCR) and consequently increases the number of measurable genes up to 25-fold by qPCR. It is suitable for cryosections from many tissues and species in order to evaluate in utero biological effects on specific effector sites. © 2014 Elsevier B.V.


Asam S.,Research Center for Nutrition and Food science | Konitzer K.,Research Center for Nutrition and Food science | Rychlik M.,TU Munich
Mycotoxin Research | Year: 2011

Cereal, fruit and vegetable products were analyzed for contamination with the Alternaria mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) using stable isotope dilution assays (SIDAs). Both toxins were practically not detected in cereals and cereal products: AOH-one out of 13 samples at a content of 4.1 μg/kg; AME-two out of 13 samples at contents ranging between 0.2 and 0.6 μg/kg. However, if cereals for animal nutrition were analyzed, much higher values were found: AOH-five out of six samples (13-250 μg/kg); AME-six out of six samples (3-100 μg/kg). This finding may pose a potential problem concerning animal health. AOH and AME were frequently detected in vegetable products: AOH-5 out of 10 samples (2.6-25 μg/kg); AME-6 out of 10 samples (0.1-5 μg/kg). Tomato products were affected, especially. The highest content of AOH (25 μg/kg) and AME (5 μg/kg) were found in triple concentrated tomato paste. Special wines like "Trockenbeerenauslese" or "Spätlese" (affected by noble rot in the vineyard) contained AOH (4/6 samples; 1.2-4.9 μg/kg) and AME (4/6 samples; 0.1-0.3 μg/kg), but the values did not exceed the values of both toxins that were found generally in wines. © 2010 Society for Mycotoxin Research and Springer.


Lopes T.J.S.,Max Delbrueck Centrum of Molecular Medicine | Luganskaja T.,Max Delbrueck Centrum of Molecular Medicine | Vujic Spasic M.,University of Heidelberg | Hentze M.W.,European Molecular Biology Laboratory EMBL | And 3 more authors.
BMC Systems Biology | Year: 2010

Background: Every cell of the mammalian organism needs iron as trace element in numerous oxido-reductive processes as well as for transport and storage of oxygen. The very versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in the cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, excretion and intra-body distribution. Intracellular regulation in different cell types is intertwined with a global hormonal signalling structure. Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole.Results: Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on ferrokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, iron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartment) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearance rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distribution into different organs, of tracer-accessible pool sizes and of residence times of iron in the different compartments in response to three states of iron-repletion induced by the dietary regime.Conclusions: This mathematical model presents a comprehensive physiological picture of mice under three different diets with varying iron contents. The quantitative results reflect systemic properties of iron metabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron storage in parenchymal organs.Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place. © 2010 Lopes et al; licensee BioMed Central Ltd.


Asam S.,TU Munich | Lichtenegger M.,TU Munich | Liu Y.,TU Munich | Rychlik M.,TU Munich | Rychlik M.,Research Center for Nutrition and Food science
Mycotoxin Research | Year: 2012

The Alternaria mycotoxin tenuazonic acid (TA) was quantified in fruit juices (n=50), cereals (n=12) and spices (n=38) using a recently developed stable isotope dilution assay (SIDA). [13C6, 15N]-TA was used as the internal standard. Method validation revealed low limits of detection (LODs) of 0.15 μg/kg (fruit juices), 1.0 μg/kg (cereals) and 17 μg/kg (spices). The respective limits of quantitation were about three times higher. Recovery was about 100% for all matrices. The precision (relative standard deviation of replicate analyses of naturally contaminated samples) was 4.2% (grape juice; 1.7 μg/kg), 3.5% (whole wheat flour; 36 μg/kg) and 0.9% (curry powder; 215 μg/kg). The median content of TA in the analyzed samples was 1.8 μg/kg (fruit juices), 16 μg/kg (cereals) and 500 μg/kg (spices). Positive samples amounted to 86% (fruit juices), 92% (cereals) and 87% (spices). © Society for Mycotoxin Research and Springer 2011.


Clavel T.,TU Munich | Duck W.,University of Alabama at Birmingham | Charrier C.,NovaBiotics | Wenning M.,Research Center for Nutrition and Food Science | And 2 more authors.
International Journal of Systematic and Evolutionary Microbiology | Year: 2010

The C3H/HeJBir mouse model of intestinal inflammation was used for isolation of a Grampositive, rod-shaped, non-spore-forming bacterium (B7 T) from caecal suspensions. On the basis of partial 16S rRNA gene sequence analysis, strain B7T was a member of the class Actinobacteria, family Coriobacteriaceae, and was related closely to Enterorhabdus mucosicola Mt1B8T (97.6 %). The major fatty acid of strain B7T was C16 : 0 (19.1 %) and the respiratory quinones were mono- and dimethylated. Cells were aerotolerant, but grew only under anoxic conditions. Strain B7T did not convert the isoflavone daidzein and was resistant to cefotaxime. The results of DNA-DNA hybridization experiments and additional physiological and biochemical tests allowed the genotypic and phenotypic differentiation of strain B7T from the type strain of E. mucosicola. Therefore, strain B7T represents a novel species, for which the name Enterorhabdus caecimuris sp. nov. is proposed. The type strain is B7T (=DSM 21839T =CCUG 56815T). © 2010 IUMS.


Oral iron supplementation with ferrous sulfate (FeSO) at dosage levels suggested by the international guidelines poses a safety hazard to young children with malaria. Exposure to loosely bound iron in the circulation has been advanced as a potential factor.To evaluate the kinetics of circulating concentrations of plasma iron and non-transferrin-bound iron (NTBI) in response to oral iron administration in healthy adults.Plasma samples were collected at 90-minute intervals over a period of 270 minutes from 10 healthy Guatemalan men after oral administration of water or 100 mg of iron from each of three iron compounds: FeSO, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), and iron polymaltose. The four tests were administered in an individually randomized sequence. Serum iron concentration was measured spectrophotometrically by the ferrozine method, and NTBI concentration was measured by a fluorometric competitive binding assay. The kinetic response and the maximal and cumulative changes in circulating concentrations of the biomarkers of interest were compared.Serum iron and NTBI responses to oral administration of FeSO were significantly greater than responses to plain water or the other two iron compounds. NTBI concentrations after NaFeEDTA or iron polymaltose ingestion were not different from those determined after water intake.Administration of two iron compounds of proven bioavailability, but with complex absorption characteristics, is associated with a negligible NTBI response, potentially mitigating the safety concerns associated with iron supplementation in malarial areas.


PubMed | Research Center for Nutrition and Food science
Type: Journal Article | Journal: Mycotoxin research | Year: 2013

Cereal, fruit and vegetable products were analyzed for contamination with the Alternaria mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) using stable isotope dilution assays (SIDAs). Both toxins were practically not detected in cereals and cereal products: AOH-one out of 13 samples at a content of 4.1g/kg; AME-two out of 13 samples at contents ranging between 0.2 and 0.6g/kg. However, if cereals for animal nutrition were analyzed, much higher values were found: AOH-five out of six samples (13-250g/kg); AME-six out of six samples (3-100g/kg). This finding may pose a potential problem concerning animal health. AOH and AME were frequently detected in vegetable products: AOH-5 out of 10 samples (2.6-25g/kg); AME-6 out of 10 samples (0.1-5g/kg). Tomato products were affected, especially. The highest content of AOH (25g/kg) and AME (5g/kg) were found in triple concentrated tomato paste. Special wines like Trockenbeerenauslese or Sptlese (affected by noble rot in the vineyard) contained AOH (4/6 samples; 1.2-4.9g/kg) and AME (4/6 samples; 0.1-0.3g/kg), but the values did not exceed the values of both toxins that were found generally in wines.

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