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Endogenous production of nitrate in patients with infective gastroenteritis is increased manifold, and this increase originates from endogenous production of nitric oxide via the enzymatic L-arginine-NO pathway. Endogenous nitrate production seems to be a specific feature of infective gastroenteritis; no significant increase is observed in non-infective diarrhoeal conditions, and the production during other infective conditions such as septicaemia is comparatively modest. Twenty four hours urinary nitrate excretion after a period of minimal oral nitrate intake is the golden standard for measuring endogenous nitrate production, but is difficult to implement and prone to sampling errors. The urinary nitrate/creatinine ratio appears a satisfactory alternative provided that a standardised collection procedure is carried out. The urinary ratio reveals differences in endogenous nitrate production that remain undisclosed with serum nitrate measurements. Addition of nitrite achieves kill of micro-organisms where acid alone allows growth to continue. The synergism in antimicrobial action of acid and nitrite is evident against common gut pathogens such as the <I>Enterobacteriaceae</I>, including <I>E. coli 0157, </I>but also against the stomach pathogen <I>H pylori, </I>normally very resistant to acid alone. The antibacterial action of acidified nitrite becomes apparent at physiological concentrations of acid and nitrite after exposure times that are within the passage time of a food bolus through the stomach. Acidified nitrite also has an antifungal effect against <I>Candida albicans, </I>however at concentrations of acid and nitrite not normally found in the human upper gastro-intestinal tract. The antimicrobial activity of acidified nitrite is enhanced by thiocyanate, also present in gastric juices. Ascorbic acid provides protection against the antibacterial action of acidified nitrite, suggesting that NO is not the antibacterial agent. Acidification of salivary nitrite in the stomach will increase host defence against ingested pathogens. Generation of salivary nitrite increases greatly after nitrate ingestion, suggesting that ingestion of foods rich in nitrate may protect against infective gastroenteritis.

L’étude des interactions hôte-pathogène permettra de mieux comprendre les bases des maladies infectieuses. Durant ma thèse, j’ai étudié les interactions entre l’organisme modèle Drosophila melanogaster et la bactérie pathogène à Gram négatif Serratia marcescens (S.m). Cette bactérie est capable de tuer les mouches en moins de 24 heures une fois introduite directement dans l’hémolymph. Au contraire, les mouches peuvent survivre plusieurs jours après avoir ingéré du Serratia malgré les dommages à l’épithélium intestinal qui en résulte. Le travail de ma thèse a mené à comprendre la virulence des vésicules de la membrane externe purifiés de S.m et injectés dans la mouche. En plus, nous avons mis en évidence deux gènes qui jouent un rôle dans la virulence de la bactérie en infection intestinale, notamment dans la capacité de S.m à endommager les cellules intestinales. Enfin, nous avons identifié plusieurs gènes impliqués dans un mécanisme de résilience de la drosophile aux infections intestinales par S.m. / The study of host-pathogen interactions will provide a better understanding of the basics of infectious diseases. During my thesis, I studied the interactions between the model organism Drosophila melanogaster and the Gram-negative pathogen Serratia marcescens (S.m). This bacterium is capable of killing flies in less than 24 hours once introduced directly into the hemolymph. On the contrary, flies can survive several days after ingesting Serratia despite he resulting damages to the intestinal epithelium. The work of my thesis led to an understanding of the virulence of the outer membrane vesicles purified from S.m and injected into the fly. In addition, we have identified two genes that play a role in the virulence of the bacterium in the intestinal infection model, particularly in the ability of S.m to damage the intestinal cells. Finally, we have identified several Drosophila genes involved in a resilience mechanism to intestinal infections by S.m.

Introduction: In low-income populations, overweight often co-exists with micronutrient deficiencies as a consequence of dietetic inadequacies and intestinal infections. Infancy is a period of increased risk for micronutrient deficiencies due to the higher nutritional demand for the physical growth. In addition, overweight during infancy is an early marker for future obesity. Objective: to investigate micronutrient and overweight markers and the association to intestinal infection and acute diarrhea among low-income infants. Methods: This was a prospective cohort study enrolling healthy infants from Laranjeiras, Sergipe, Brazil. Children underwent anthropometry to obtain anthropometric indexes and blood assays for hemoglobin, ferritin, C-reactive protein, plasma selenium, plasma and erythrocyte zinc and copper concentrations every 6 months of follow up. Stool samples were collected monthly and every acute diarrhea episode to verify the presence of rotavirus, helminths and protozoans. Results: At enrolment the mean age was 6.6 ± 2 months, 2% of children were stunted, 2% wasted, 24% had risk of overweight and 7% were overweight or obese. 68% of children were anemic, 40% had iron deficiency, 57% and 51% had low plasma and erythrocyte zinc, 5% and 82% low plasma and erythrocyte copper, and 91% had low plasma selenium concentrations. The prevalence of anemia and iron deficiency decreased after iron supplementation, although the prevalence of trace element deficiencies remained elevated throughout the follow up. Stable overweight periods and rapid weight gain were predictors of preschool age overweight and adiposity. The number of acute diarrhea episodes was negatively associated to plasma ferritin and zinc concentrations, and the number of any intestinal infection was negatively associated to middle upper arm circumference for age. Conclusion: it was observed a dual nutritional problem in this population, characterized by the higher proportion of overweight related to underweight, and by elevated frequency of anemia and low concentrations of iron, zinc, copper and selenium biomarkers. Intestinal infection was associated to decreased body mass, and acute diarrhea was associated to plasma ferritin and zinc deficiency. / Introdução: Em populações pobres, o sobrepeso frequentemente co-existe com deficiência de micronutrientes, devido à má alimentação e às frequentes enteroinfecções a que essas populações estão expostas. Os lactentes são grupo de risco para o desenvolvimento de carências de micronutrientes devido à elevada demanda nutricional imposta pelo crescimento, e o sobrepeso nessa faixa etária pode representar risco de obesidade em idades futuras. Objetivo: investigar marcadores de micronutrientes e de sobrepeso, e associações com patógenos intestinais e diarreia aguda em lactentes que vivem em condições de vulnerabilidade. Métodos: Trata-se de estudo de coorte prospectivo, com seguimento de 18 meses, envolvendo lactentes saudáveis residentes no município de Laranjeiras, Sergipe, Brasil. Foi feita avaliação de índices antropométricos e dosagem de hemoglobina, ferritina plasmática, proteína C reativa, zinco plasmático e eritrocitário, cobre plasmático e eritrocitário e selênio plasmático, no início e a cada seis meses de seguimento. Foram colhidas amostras de fezes mensais e a cada episódio de diarreia aguda para verificar a presença de rotavirus, helmintos e protozoários. Resultados: no início do estudo as crianças tinham média de idade de 6,6 ± 2 meses e 2% apresentaram déficit de estatura, 2% déficit de peso, 24% risco de sobrepeso e 7% apresentaram sobrepeso ou obesidade. 68% das crianças tinham anemia, 40% deficiência de ferro, 57% e 51% baixa concentração de zinco plasmático e eritrocitário, 5% e 82% baixa concentração de cobre plasmático e eritrocitário, e 91% baixa concentração de selênio. As prevalências de anemia e de deficiência de ferro reduziram ao longo do estudo com a suplementação de ferro, mas as prevalências de deficiência dos elementos-traço se mantiveram elevadas em todo o seguimento. Episódios estáveis de sobrepeso e o rápido ganho de peso estiveram associados a maior risco de sobrepeso e adiposidade no início da idade pré-escolar. O número de episódios de diarreia aguda esteve associado de forma negativa à concentração de ferritina e de zinco plasmáticos, e o número de enteroinfecções esteve associado de forma negativa ao índice circunferência braquial/idade. Conclusão: foi evidenciado extremos nutricionais nessa população, caracterizados por maior proporção de sobrepeso do que de baixo peso, e alta prevalência de anemia e de deficiência de biomarcadores de ferro, zinco, cobre e selênio. Os enteropatógenos estiveram associados ao declínio da massa corporal, e a diarreia aguda exerceu efeito negativo sobre o estado de ferro e de zinco dos lactentes avaliados.