High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults

PMCID: PMC3897937This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Abdication de Charles-Quint par M. Louis Gallait

Copia digital : Junta de Castilla y León. Consejería de Cultura y Turismo, 201

Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea

Background: Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia. Methods/Principal findings: We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013). Conclusions/Significance: Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization

Dynamics of the photo-induced desorption and oxidation of CO on Ru(0001) with different (O, CO) coverages

244 p.Carbon monoxide (CO) is a neurotoxic gas emitted for instance in combustion reaction. Therefore it hasbeen sought for air treatment solution, where CO oxidation is a straight forward choice. In ultra highvacuum conditions the ruthenium has been found to be very inactive for CO oxidation. Experimentally ithas been shown the opening of a new reaction path for CO oxidation on ruthenium surfaces by means offem to second laser irradiation. Accurate simulations of the photo-reaction dynamics are required to give aproper characterization of this kind of experiments. This thesis is dedicated to the study of the photo induced desorption and oxidation of CO molecules, coadsorbed with oxygen (O) adatoms on Ru(0001)with different surface coverages. We began with the characterization of three (O, CO) mixed surface coverages on Ru(0001). We first found the adsorption configuration of minimum energy for each surface coverage, then we computed the desorption potential of a CO molecule, and found the minimum energy path to CO oxidation on all three surface coverages. Then we ran ab-initio molecular dynamics with electronic friction simulations, and we have been able to show the complexity of the reaction path to oxidize the CO molecule, and explain its low probability of occurrence. Next, we showed the importance of surface deformations on the desorption and oxidation probabilities of CO, and on the adsorbat emotion. Then, we have shown in detail and characterized the different mechanisms of CO oxidation.Finally we created a potential energy surface based on neural networks and showed that it is a very promising tool to solve the problem of the computational cost of ab-initio molecular dynamics simulations

Three-hole microstructured optical fiber for efficient Fiber Bragg Grating refractometer

International audienceWe present a photosensitive three-hole microstructured optical fiber specifically designed to improve the refractive index sensitivity of a standard Fiber Bragg Grating (FBG) sensor photowritten in the suspended Ge-doped silica core. We describe the specific photowriting procedure used to realize gratings in such a fiber. We then determine their spectral sensitivity to the refractive index changes of material filling the holes surrounding the core. The sensitivity is compared to that of standard FBGs photowritten in a six-hole fiber with a larger core diameter. We demonstrate an improvement of the sensitivity by two orders of magnitude and reach a resolution of 3 x 10-5 and 6 x 10-6 around mean refractive index values of 1.33 and 1.40, respectively

AMINO ACID AND / OR MULTIPLE MICRONUTRIENT SUPPLEMENTATION IN ENVIRONMENTAL ENTEROPATHY: EFFECTS ON SMALL INTESTINAL BARRIER STRUCTURE AND FUNCTION

PhDEnvironmental enteropathy (EE) is thought to underlie stunting, a widely prevalent phenomenon in the developing world with lifelong detrimental consequences. EE is characterised by increased intestinal permeability and reduced absorptive capacity in a chronically inflamed gut, and occurs in nutritionally vulnerable populations. Deficits of amino acids and micronutrients may cause intestinal immune and barrier dysfunction, mediated through cellular nutrient sensing pathways. Mechanistic target of rapamycin complex 1 (MTORC1) is the most important of these, and is of particular interest in EE due to its roles in both epithelial and immune cell function. It was hypothesised that supplementation with the amino acids (AA) L-Glutamine, L-Tryptophan and L-Leucine +/- high dose multiple micronutrients (MM) could modify the abnormal small intestinal histology and permeability seen in EE, and would modify lamina propria lymphocyte (LPL) MTORC1 signalling. A randomised controlled trial was therefore undertaken. Assessments of many of the pathophysiological domains of EE (absorptive area; mucosal inflammation; microbial translocation; permeability; systemic immune activation; host-microbiota interactions; enterohumoral signalling), as well as LPL MTORC1 signalling, were performed in 84 healthy adult Zambians with EE before and after 16 weeks’ supplementation. AA supplementation improved villus height, whereas AA with MM supplementation improved in vivo barrier permeability. Supplementation did not affect LPL MTORC1 signalling; however, MTORC1 activity correlated with villus height and the size of the LP TH1 population. Metabonomics identified several potentially relevant metabolites which were upregulated by the interventions. Of note, other observed abnormalities (e.g. elevated translocation/activation markers; depressed levels of GLP2) did not change with supplementation and were mainly not correlated with the improvements in histology and permeability, suggesting that one or more pathophysiological domains (e.g. absorptive area; permeability) may be independently modifiable. These results and others explored in this thesis provide new insights into the complex relationship between nutrition, intestinal health, and EE.I gratefully acknowledge the support of CORE & the Nutritional Research Foundation who funded this work through a research training fellowship grant, and the Bill & Melinda Gates Foundation who funded the metabonomics work

Fiabilité d'une liste minimale de descripteurs agromorphologiques recommandée par le COGENT dans l'étude de la diversité génétique du cocotier.

L'objectif de cette étude est de tester, dans les conditions agroclimatiques de la Côte d'Ivoire, la fiabilité de la liste minimale de 20 descripteurs (17 quantitatifs et 3 qualitatifs) proposée par le Coconut Genetic Resources Network (COGENT) en 2007 pour l'étude de la diversité agromorphologique des populations de cocotier. Il s'agit des descripteurs hauteur du stipe (HAUT), circonférence du bulbe ou du stipe à 20 cm du sol (C20), circonférence du stipe à 150 cm du sol (C150), la longueur entre 11 cicatrices foliaires sur le stipe (L11CF), nombre de fleurs femelles (NBFF), le nombre d'épillets (NEP), la masse de la noix (MN), masse de la noix débourrée (MND), la masse de la bourre (MB), la masse de l'eau (ME), la masse de la coque (MC), masse de l'albumen (MALB), épaisseur de l'albumen (EA), masse de coprah par noix (CN), teneur en huile de l'albumen séché (HS), nombre de régime par arbre par an (NRAA), nombre de noix par arbre par an (NFAA), couleur du fruit immature (CFim), forme de la section polaire du fruit (FPF) et forme de la noix débourrée (FND). Ainsi, la variabilité phénotypique des caractères qualitatifs et quantitatifs a été évaluée chez 11 populations de cocotiers Grand. De même, la diversité agromorphologique générée par une longue liste de 50 descripteurs quantitatifs a été confrontée avec celle des 17 recommandés par le COGENT. Excepté les caractères liés à la feuille, une très grande variabilité a été observée dans l'expression des caractères liés au fruit, à l'inflorescence et au stipe. De même, l'alternative de l'utilisation des caractères qualitatifs décrivant les formes de la noix débourrée et de la section polaire du fruit pour la caractérisation des populations de cocotier Grand semble justifiée puisque ces deux caractères présentent un polymorphisme élevé. La description et la structuration de la diversité des populations de cocotiers Grand étudiées à partir de la liste réduite de 17 descripteurs quantitatifs et de celle de 50 descripteurs ont été similaires. Ainsi, l'adoption de la liste minimale de 17 descripteurs quantitatifs établis par le réseau COGENT comme liste standard de descripteurs agromorphologiques permettra un gain de temps considérable dans l'évaluation des collections au champ, facilitera les échanges, les comparaisons et l'utilisation des informations biologiques sur les ressources génétiques de cocotier à travers le monde. (Résumé d'auteur

Fiber Optic Sensing System for Temperature and Gas Monitoring in Coal Waste Pile Combustion Environments

International audienceIt is presented an optical fiber sensing system projected to operate in the demanding conditions associated with coal waste piles in combustion. Distributed temperature measurement and spot gas sensing are requirements for such a system. A field prototype has been installed and is continuously gathering data, which will input a geological model of the coal waste piles in combustion aiming to understand their dynamics and evolution. Results are presented on distributed temperature and ammonia measurement, being noticed any significant methane emission in the short time period considered. Carbon dioxide is also a targeted gas for measurement, with validated results available soon. The assessment of this technology as an effective and reliable tool to address the problem of monitoring coal waste piles in combustion opens the possibility of its widespread application in view of the worldwide presence of coal related fires

The role of the gut microbiome in Major Depressive Disorder

The aetiology of major depressive disorder (MDD) is poorly understood. Current evidence suggests immune activation and gut microbiota may play a role. Recent studies demonstrated that behavioural traits can be transferred through microbiota transplantation into germ-free (GF) mice. Here we study whether microbiota from patients with MDD can induce depressive-like behaviour. Methods: GF NIH Swiss mice were colonized with stool microbiota from a patient with MDD with elevated faecal β-defensin 2, or a healthy donor (HC). After three weeks, behaviour was assessed using standard tests. Expression of neuroimmune markers was assessed in the gut and brain using gene expression profiling and immunohistochemistry. Microbiota composition was assessed by 16S rRNA sequencing. Results: Microbiota profiles differed between the two groups of mice (p=0.001). Mice colonised with microbiota from a single characterised MDD patient (MDD1), exhibited lower preference for sucrose (p=0.002) and more emotionality (p=0.003) than mice with HC microbiota, however other MDD mice did not display abnormal behaviour. Abnormal MDD1 behaviour was associated with lower BDNF expression in the dentate gyrus of the hippocampus (p=0.02). Mice colonised with another characterised MDD patient (MDD4 mice) did not have differences in BDNF expression in the same region (p=0.20). MDD1 and MDD4 mice had altered hippocampal and gut gene expression for genes associated with the immune and nervous system. In summary, GF mice colonized with MDD1 microbiota exhibit depression-like behaviors. This appears to be accompanied by changes in intestinal permeability and neuroimmune function. These results suggest that gut microbiota has the capacity to influence the expression of MDD in some patients.ThesisMaster of Science (MSc

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE