Os grãos de linhaça e amaranto recebem grande atenção da população em decorrência de suas alegações nutricionais e funcionais à saúde. Uma vez que estes grãos apresentam significativos teores de fibras alimentares (28 e 10%, respectivamente), os efeitos fisiológicos benéficos associados a estas frações foram investigados por meio de parâmetros do metabolismo colônico (fermentativos) e lipídico em ensaio biológico com ratos (Wistar), divididos em quatro grupos (n=12) durante 28 dias. As dietas dos grupos Referência e Controle apresentaram 7% (p/p) de celulose, e as dietas dos grupos experimentais foram formuladas com: farinha desengordurada de linhaça; amaranto extrusado, de modo que apresentassem 7% de fibra alimentar (FA). Com exceção da dieta do grupo Referência, as demais apresentaram 0,5% de colesterol (p/p). Foram observados para os grupos Linhaça e Amaranto: aumento do peso do ceco e conteúdo; aumento da massa fecal úmida; aumento dos ácidos graxos de cadeia curta (AGCC) e diminuição do pH no conteúdo do ceco, indicando fermentação colônica. Os animais do grupo Linhaça apresentaram menor peso e colesterol hepático, porém, nenhuma alteração no colesterol plasmático e na excreção de colesterol e ácidos biliares nas fezes. Já os animais do grupo Amaranto apresentaram menor peso hepático, porém, nenhuma alteração do colesterol total do órgão. Neste grupo também não foi observada redução do colesterol plasmático, acompanhada do aumento da excreção do colesterol e redução dos ácidos biliares nas fezes. Sugere-se que o trofismo da parede do ceco está relacionado à produção de ácido butírico, principal substrato energético dos colonócitos, que contribui para uma mucosa mais resistente a patógenos e carcinógenos. O mecanismo envolvido no efeito hepatoprotetor observado no grupo Linhaça pode estar relacionado à produção de ácido propiônico no cólon, uma vez que a literatura sugere que o mesmo pode estar envolvido na inibição da HMG-CoA redutase. Desconhecem-se, até o momento, os mecanismos que promoveram a menor excreção de ácidos biliares nas fezes no grupo Amaranto. De qualquer modo, as FAs do grão de linhaça e amaranto não foram capazes de promover efeito hipercolesterolemiante nas condições em que foi realizado este estudo. Conclui-se que as frações indigeríveis da linhaça e amaranto são benéficas para a saúde da mucosa intestinal. / The flaxseed and amaranth grains are recognized by their nutritional and functional health attributes. These grains have significant contents of dietary fiber (28 and 10%, respectively), and the physiological effects related to these fractions were investigated by colonic fermentative and lipid metabolism parameters with rats (Wistar) distributed in five groups (n=12) during twenty-eight days. The diets of the Reference and Control groups contained 7% (w/w) of cellulose and the diets of the experimental groups were formulated with: defatted flaxseed flour and defatted extruded amaranth, in order to provide 7% dietary fiber (DF). With the exception of the Reference, the other diets received 0,5% cholesterol. The Flaxseed and Amaranth groups compared to the Control showed: greater weight of caecum and its contents; greater weight of feces (wet mass); increase of short chain fatty acids (SCFA) concentration and decrease of pH of cecal content, indicating colonic fermentation. The Flaxseed group showed lower liver hepatic weight and cholesterol, but no changes in plasmatic cholesterol, cholesterol fecal excretion, or bile acids fecal excretion. The Amaranth group exhibited lesser hepatic weight, along with no changes on hepatic cholesterol. Also, no plasma cholesterol reduction was observed, with the increase of fecal cholesterol excretion and decrease in fecal bile acid excretion. It is suggest that the caecum wall trophism was related to butiric acid production, main energy colonic cell substrate that fosters a more resistant mucosa to pathogens and carcinogens. The mechanism involved in liver protecting effect, observed in the Flaxseed group, could be related to propionic acid production, since that it is suggest in the literature that this fatty acid could be envolved in the HMG-CoA reductase inhibition. Until this moment, the mechanisms that promoted the lesser bile acid excretion by the Amaranth group were not kwon. The DFs of flaxseed and amaranth grains were unable to promote hypocholestelolemic effects under the present assay conditions. It could be concluded that DFs of flaxseed and amaranth grains are beneficial to the health of the intestinal mucosa.

O objetivo do presente trabalho foi avaliar a preservação da inervação de porções intestinais macroscopicamente viáveis em cães portadores de intussuscepções. Para tanto, realizou-se comparação entre segmento intestinal proveniente deste grupo de animais (G1) e segmentos intestinais de animais sem qualquer distúrbio do aparelho digestório (G2). Avaliações histológicas e imunoistoquímicas foram realizadas em sistema computadorizado (Image Pro-Plus®) além da avaliação tardia da qualidade de vida e função digestiva. As variáveis analisadas foram: densidade média das camadas musculares circular e longitudinal, relação entre as camadas musculares, número média de plexos mioentéricos, densidade celular média dos plexos mioentéricos, grau de degeneração neuronal nos plexos mioentéricos, imunoreatividade à sinaptofisina e ao NSE além de existência de distúrbios de defecação. Com exceção da densidade celular média da camada longitudinal, relação entre as camadas musculares e imunoreatividade à sinatpofisina, todos os demais parâmetros apresentaram diferença estatisticamente significativas entre os grupos testados. Foram observadas correlações entre densidade celular média dos plexos mioentéricos e densidade celular média da camada muscular circular; grau de vacuolização dos plexos mioentéricos e imunoreatividade ao NSE; além de grau de vacuolização dos plexos mioentéricos e densidade celular média dos plexos mioentéricos. Quanto aos anticorpos utilizados, o NSE apresentou melhor padrão de marcação quando comparado à sinaptofisina. Dos 13 cães pertencentes ao G1, três foram a óbito no pós-operatório inicial. No período pós-operatório tardio, três cães apresentaram alterações de consistência e freqüência de defecação, além de episódios diarréicos agudos intermitentes. O tempo de segmento foi de 6 meses após intervenção cirúrgica. Os achados deste estudo sugerem que porções intestinais macroscopicamente viáveis podem apresentar lesões de inervação eventualmente traduzidas em sintomatologia clínica futura. Assim sendo, deve-se avaliar de maneira cuidadosa a margem cirúrgica preservada durante o procedimento de enterectomia/enteroanastomose bem como realizar acompanhamento da função digestória tardia. / The purpose of this study was to evaluate the preservation of the innervation of macroscopically viable bowel segments of dogs with intussusceptions. This group (G1) was compared to bowel segment of normal dogs (G2). Histological and immunohistochemical analysis were performed using computed system (Image Pro-Plus®). Late assessment of the quality of life and digestive function were also evaluated. Analyzed variables included: mean density of circular and longitudinal muscular layers cells, ratio between muscular layers, mean of myenteric plexuses, mean density of myenteric cells, neuronal degeneration degree in myenteric plexus, synaptophysin and NSE immunoreactivity and defecatory disorders. All tested parameters, except mean density of longitudinal muscular layers cells, ratio between muscular layers and synaptophysin immunoreactivity, showed statistical differences when group G1 was compared with group G2. Correlations between mean density of myenteric cells and mean density of circular muscular layers cells; neuronal degeneration degree in myenteric plexus and NSE immunoreactivity; neuronal degeneration degree in myenteric plexus and mean density of myenteric cells were observed. Regarding the immunohistochemical antibodies, NSE showed better staining pattern than synaptophysin. Three animals of G1 (n=13) died during the initial post-operative period. During the late post-operative period, three animals presented disorders in fecal consistency, frequency of defecation and acute intermittent diarrheal episodes. The follow-up time was 6 months. These findings showed that macroscopically viable bowel segments can present innervation damage eventually translated in clinical symptoms in the future. So, a careful evaluation of the preserved surgical margin during enterectomy and enteroanastomosis must be carried out as well as monitoring of the late digestive function.

Orientador: José Antonio Rocha Gontijo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T06:22:30Z (GMT). No. of bitstreams: 1 Possignolo_LuizFernando_M.pdf: 4767580 bytes, checksum: b843458e4c7049fc29741e4aca9f918d (MD5) Previous issue date: 2012 / Resumo: Devido ao maior consumo de alimentos ricos em gordura e um estilo de vida mais sedentário, houve um aumento na incidência de desordens metabólicas relacionadas ao metabolismo lipídico como a resistência à insulina, dislipidemias, e sua associação com doenças cardiovasculares. A alimentação materna desequilibrada, durante a gestação e lactação, pode predispor a prole à doenças durante a vida adulta. Alguns transportadores como o Scavenger Receptor class B type I (SR-BI) e ATP-binding cassette transporter A1 (ABCA1) são descritos como responsáveis pela captação de colesterol e transporte deste a partir de lipoproteínas, principalmente no transporte reverso de colesterol, sendo denominados receptores antiaterogênicos podendo modificar seu padrão de expressão frente a uma dieta hiperlipídica. Ratas Wistar receberam dieta hiperlipídica (DHL) ou dieta padrão (CTL) desde o desmame, até a lactação. Após o desmame a prole de machos recebeu a dieta padrão até a 16ª semana de vida. Nas mães quanto e na prole foram analisados os seguintes parâmetros: ingestão alimentar, ganho ponderal, perfil lipídico e glicídico. Na prole foi estudada a expressão e localização de ABCA1 e SR-BI na placenta, no rim, fígado, e intestino delgado em animais com 17 dias pré-natal (E17), 12 dias pós-natal (PN12d) com 8 e 16 semanas pós-natal (PN8s e PN16s). As mães DHL apresentaram: 1) maior ingestão calórica com menor ganho ponderal; 2) aumento glicêmico associado à menor produção de insulina nos três períodos estudados e, 3) aumento nos níveis séricos de triglicérides em M8s. A prole de mães DHL apresentaram menor massa corporal desde E17 até PN8s, sem que tenha havido diferenças ponderais e na ingestão de ração. PN8s e PN16S apresentaram menor captação tissular de glicose associada à hiperinsulinemia, e aumento nos níveis séricos de triglicérides com PN16S. Não houve alterações nos níveis de colesterol e HDLcolesterol. Não foi observada alteração na expressão de SR-BI e ABCA1 no intestino delgado, placenta enquanto no fígado houve uma queda tempo-dependente para ambos transportadores. No rim da prole DHL aos PN12d e PN16s observou-se maior expressão de ABCA1. Este estudo mostrou que o consumo materno crônico de uma dieta hiperlipídica causa alterações metabólicas nas mães e predispõe a prole, a modificações no metabolismo lipídico e glicídico, além de elevação da expressão de ABCA1 no rim / Abstract: Due to the abundance and accessibility to foods high in fat and a more sedentary lifestyle, there is an increased incidence of metabolic disorders related to lipid metabolism such as insulin resistance, dyslipidemia, and a high correlation with cardiovascular disease. The unbalanced maternal diet during pregnancy and lactation predisposes the offspring to diseases during adult life. Some carriers such as scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter A1 (ABCA1) are described as responsible for raising cholesterol and transporting it to and from lipoproteins, due the participation in the reverse cholesterol transport, these receptors are called antiatherogenic and are subject to change its pattern of expression when exposed to a high fat diet. Female Wistar rats were fed a diet (HFD) or a standard chow (CTL) from weaning, during pregnancy and lactation. After weaning the male offspring was exposed to a standard chow until the 16th week of life. Both the dams and the offsprings food intake were monitored, weight gain, lipid profile and glucose level. It was analyzed in the offspring the expression and localization of ABCA1 and SR-BI in the placenta, kidney, liver, and small intestine in animals at 17º prenatal day (E17), 12 days post-natal (PN12d), 8 and 16 postnatal weeks (PN8s PN16s respectively). DHL dams had a higher intake of calories in the diet, but the weight was smaller, they had higher blood glucose due to decreased production of insulin in the pre-pregnancy (m8s), during pregnancy (M17g) and lactation (M15l) and a higher triglyceride level in m8s. The offspring of dam fed a high fat diet had lower weight since E17 until PN8s, with no differences in weight gain and food intake. PN8s and PN16s had lower glucose uptake and hyperinsulinemia, and high triglycerides with PN16s, no changes were observed in cholesterol and HDL-cholesterol levels. There were no changes in the expression of SR-BI and ABCA1 in the small intestine, placenta and liver, however there was a decrease over the age for both receptors, and kidney of the offspring and DHL PN12d PN16s showed higher expression of ABCA1. The present study showed that chronic consumption of high fat diet causes metabolic changes in dams and predisposes offspring to changes in lipid and glucose metabolism of the offspring, increasing the expression of ABCA1 in the kidney / Mestrado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Mestre em Fisiopatologia Médica

Orientador: Wirla Maria da Silva Cunha Tamashiro / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T10:43:40Z (GMT). No. of bitstreams: 1 Ruberti_Maristela_D.pdf: 10774061 bytes, checksum: 7afe7ee8aa8c7f97c1f80e66f0cd8bfa (MD5) Previous issue date: 2012 / Resumo: Trabalhos anteriores de nosso laboratório mostraram que camundongos transgênicos DO11.10, cuja maioria dos linfócitos T expressam TCR específico para ovalbumina (OVA) no contexto de...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Previous work from our laboratory showed that DO11.10 transgenic mice, in which the most of T lymphocytes express TCR specific for ovalbumin (OVA) in the context of...Note: The complete abstract is available with the full electronic document / Doutorado / Imunologia / Doutor em Genetica e Biologia Molecular

Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2015-03-20T22:54:55Z No. of bitstreams: 2 Efeito da associação entre os probióticos Saccharomyces boulardii e Bacilus cereus var. Toyoi sobre a proteção contra desafio com Salmonella Typhimurium em camundongos.pdf: 950556 bytes, checksum: d9746b0e55dab14349d49ea0ff188774 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2015-03-20T23:36:20Z (GMT) No. of bitstreams: 2 Efeito da associação entre os probióticos Saccharomyces boulardii e Bacilus cereus var. Toyoi sobre a proteção contra desafio com Salmonella Typhimurium em camundongos.pdf: 950556 bytes, checksum: d9746b0e55dab14349d49ea0ff188774 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2015-03-20T23:36:52Z (GMT) No. of bitstreams: 2 Efeito da associação entre os probióticos Saccharomyces boulardii e Bacilus cereus var. Toyoi sobre a proteção contra desafio com Salmonella Typhimurium em camundongos.pdf: 950556 bytes, checksum: d9746b0e55dab14349d49ea0ff188774 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-03-20T23:36:52Z (GMT). No. of bitstreams: 2 Efeito da associação entre os probióticos Saccharomyces boulardii e Bacilus cereus var. Toyoi sobre a proteção contra desafio com Salmonella Typhimurium em camundongos.pdf: 950556 bytes, checksum: d9746b0e55dab14349d49ea0ff188774 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-11-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Este trabalho teve por objetivo avaliar o efeito da associação entre os probióticos Saccharomyces boulardii e Bacillus cereus var. Toyoi sobre a proteção e a sobrevivência de camundongos contra a colonização intestinal, translocação e lesões intestinais após desafio com S. Typhimurium. Os animais foram alimentados 20 dias com rações contendo S. boulardii e B. Toyoi, administrados individualmente ou em associação, nas concentrações de 8 e 7 log UFC. g-1 de ração, respectivamente. Animais do grupo controle receberam ração comercial sem probióticos. No 10º dia após o início da administração dos probióticos, os animais foram desafiados por gavagem com 5,17 log UFC de S. Typhimurium (DL50). Proteção contra colonização de S. Typhimurium foi avaliada após eutanásia dos camundongos que sobreviverem após 10 dias, através de contagens de células viáveis do patógeno presentes nas fezes e intestino delgado. Para a avaliação da ocorrência de translocação, 2/3 dos órgãos (fígado e baço) foram macerados, ressuspensos em 1 mL de solução salina a 0,9% estéril e contagens de células viáveis do patógeno, em UFC.ml-1, foram realizadas em placas de XLD. Para a avaliação da ocorrência de lesão, 1/3 do intestino delgado foi avaliado através de histopatologia. O experimento foi repetido duas vezes. S. boulardii não protegeu os camundongos da morte induzida por S. Typhimurium e da ocorrência de lesões intestinais. Não houve sinergismo entre os dois micro-organismos avaliados. Entretanto, S. boulardii, assim como B. Toyoi reduziram a eliminação de S. Typhimurium pelas fezes e preveniram a translocação do patógeno para o fígado dos camundongos que sobreviveram ao desafio. B. Toyoi protegeu os animais da morte induzida pela infecção com S. Typhimurium e da ocorrência de lesões e o efeito obtido pela associação, ocorreu, provavelmente, devido somente ao efeito de B. Toyoi. Assim, novos estudos serão realizados para avaliar os efeitos da associação destes probióticos frente ao desafio com S. Typhimurium e para avaliar as causas do efeito antagônico apresentado entre eles sobre a persistência deste patógeno nas fezes dos animais e sobre a translocação para o fígado. / This study aimed to evaluate the effect of the association between the Saccharomyces boulardii and Bacillus cereus var. Toyoi probiotics on the survival and protection of mice against the occurrence of intestinal colonization, translocation and intestinal lesions after the challenge with S. Typhimurium. The animals were fed for 20 days with diet containing S. boulardii and B. Toyoi, administered individually or in association, in the food concentrations of 8 and7 log CFU. g-1, respectively. The control group animals were fed with commercial food without probiotics. On the 10th day after the start of administration of probiotics, the animals were challenged by the gavages with 5.17 log CFU of S. Typhimurium (LD50). Protection against colonization of S. Typhimurium was evaluated after euthanasia of the mice, which survived after 10 days, through the viable cell counts of the pathogen presented in the small intestine and stool. To evaluate the incidence of translocation, 2/3 of the organs (liver and spleen) were macerated, and resuspended in 1 ml of saline solution in 0.9% sterile, and viable cell counts of the pathogen were performed. To evaluate the occurrence of injury, 1/3 of the small intestine was evaluated through histopathology. The experiment was repeated twice. S. boulardii did not protect the mice from induced death by S. Typhimurium and the occurrence of intestinal lesions. For this reason, it was not possible to assess the occurrence of synergism between the two micro-organisms evaluated. However, S. boulardii as well as B. Toyoi reduced the elimination of S. Typhimurium through the stool and prevented the translocation of the pathogen to the liver of mice that survived the challenge. B. Toyoi protected animals from induced death through the infection with S. Typhimurium and through the occurrence of injuries, and the effect obtained by the association was, probably, due only by the effect of B. Toyoi. Thus, further studies will be conducted to evaluate the effects of the combination of these probiotics facing the challenge with S. Typhimurium and to assess the causes of the antagonistic effect presented among them on the persistence of this pathogen in the stool of animals and on the translocation to the liver.

A l`heure où le cancer a supplanté les maladies cardiovasculaires en tant que première cause de mortalité en France, le CCR représente la deuxième cause de mortalité par cancer. Longtemps dominé par la génétique, le paradigme du cancer colorectal a récemment évolué laissant une place prépondérante aux facteurs environnementaux. Il est néanmoins difficile d’étudier l’impact de l’environnement sur la carcinogénèse colorectale de façon exhaustive compte tenu de la multiplicité de ces facteurs environnementaux. Dans la présente étude, nous avons essayé d’appréhender la contribution de la composition du microbiote intestinal, de la composition métabolomique des eaux fécales et des altérations épigénétiques de l’hôte comme témoin de ces facteurs environnementaux au cours de la carcinogénèse colorectale et d’en évaluer le bénéfice en tant que marqueur diagnostique non invasif. Nous avons ainsi pu montrer au sein d’une population de patients à risque moyen de cancer colorectal qu’il existait une signature microbiologique, métabolomique et épigénétique spécifique du cancer colorectal. Nous avons également pu montrer que ces marqueurs présentaient des performances diagnostiques supérieures au test colorimétrique au guaiac utilisé dans le dépistage organisé du cancer colorectal. / Colorectal cancer (CRC) is a significant cause of morbidity and mortality in developed countries. The majority of CRC are called sporadic, meaning they are due to environmental factors rather than constitutional genetic alterations. Indeed, the role of environment, i.e. western lifestyle, is also underlined by dramatic geographic variations in CRC incidence in both sexes. However, it is difficult to take into account the totality of human environmental exposures for a better understanding of the colorectal cancer pathogenesis. In the present work, we tried to highlight the contribution of the environment in the development of colorectal cancer by studying the role of the intestinal microbiota together with the role of the fecal metabolites and the presence of epigenetic alterations of the host. We also investigated the performance accuracy of the latter changes for colorectal cancer diagnosis as compared to the guaiac fecal occult blood test which is widely used as a non-invasive test in several screening program. We demonstrated a specific signature associated with advanced colorectal neoplasia for the intestinal microbiota and the fecal metabolite profile for colorectal cancer as well as a link between colorectal cancer and Wif-1 gene methylation in urine and/or fecal samples. Those specific signatures disclosed higher diagnostic accuracy compared to guaiac fecal occult blood test as colorectal cancer screening test.

L’accident de désaturation (ADD) est un accident de plongée lié à la charge en gaz diluants pendant la plongée, et à la formation de bulles dans l’organisme au cours de la décompression. Il est susceptible d’engendrer des séquelles neurologiques. Au cours de plongées utilisant l’hydrogène comme gaz diluant, la diminution de la charge tissulaire en hydrogène par l’inoculation au niveau de l’intestin de bactéries métabolisant ce gaz réduit le risque d’ADD.L’objectif de ce travail était d’évaluer si inversement : 1) la fermentation intestinale lors de la plongée peut favoriser la survenue d’un ADD, par l’intermédiaire de la production d’hydrogène endogène ; 2) la stimulation chronique de la fermentation avant plongée majore le risque d’ADD.Nos résultats sont en faveur d’un effet dual de la fermentation intestinale sur la décompression. Délétère à court terme lors de la plongée, la fermentation intestinale prolongée pourrait être favorable en dehors de la plongée en prévenant la survenue et la sévérité d’un ADD. L’hydrogène, molécule aux propriétés antioxydantes, et le butyrate, un acide gras à chaîne courte, sont en effet deux produits de la fermentation des hydrates de carbone qui ont des vertus neuroprotectrices.La prévention des accidents de désaturation pourrait passer par une exclusion des plongeurs présentant une fermentation importante le jour de la plongée, une élimination des gaz produits au niveau de l’intestin ou une modification de l’alimentation dans les 24 heures précédant une plongée. En revanche, tous les facteurs susceptibles de modifier le microbiote intestinal et d’augmenter la fermentation, en dehors de la plongée, pourraient être testés en prévention de l’ADD. En outre, l’hydrogène et le butyrate pourraient jouer un rôle bénéfique dans le cadre du traitement de l’ADD / Decompression sickness (DCS) is a diving accident related to the dissolution of diluent gas in blood and tissues during a dive, followed by bubble formation in the body during decompression. It can lead to neurological damage. In dives using hydrogen as the diluent gas, the concentration of hydrogen in the tissues can be reduced by the presence in the gut of bacteria capable of metabolising this gas and this reduces the risk of DCS.The aim of this work was conversely to check if: 1) fermentation in the gut at the time of diving could exacerbate DCS as a result of endogenous hydrogen generation; 2) long-term stimulation of fermentation before diving raises the risk of DCS.Our findings point to a two-edged effect of intestinal fermentation on decompression: although deleterious in the short term, i.e. at the time of diving, longer-term intestinal fermentation between dives might have a positive effect by preventing the occurrence of DCS and limiting its severity. Indeed, hydrogen which has antioxidant properties and butyrate, a short-chain fatty acid, are both by-products of the fermentation of carbohydrate and both have neuroprotective activity.DCS prevention could be promoted by excluding divers exhibiting strong fermentation on the day of a dive, by the elimination of gases being produced in gut or by modification of diet in the 24 hours before a dive. On the other hand, any factor that might affect the gut microbiota and stimulate fermentation between dives could be tested to investigate its potential in protecting against DCS. Furthermore, hydrogen and butyrate could play a positive role when it comes to treating DCS

Les Escherichia coli entérohémorragiques (EHEC) sont des pathogènes zoonotiques responsables de toxi-infectionsalimentaires pouvant évoluer vers des atteintes potentiellement mortelles chez l’Homme. La survie des EHECet l’expression des gènes de virulence dans l’environnement digestif humain sont des facteurs essentiels dans laphysiopathologie de ces infections mais sont mal connus, essentiellement par manque de modèles d’études adaptés.L’absence de traitement spécifique a conduit à s’intéresser à des moyens préventifs et/ou curatifs alternatifs, commel’utilisation de probiotiques. L’objectif de ce travail de thèse est d’étudier le comportement de souches EHEC dansl’ensemble du tractus digestif et l’influence de souches probiotiques, en utilisant des approches in vitro et in vivocomplémentaires.In vitro, dans le tractus gastro-intestinal supérieur, on observe une mortalité bactérienne dans l’estomac, suivie d’unereprise de croissance dans les parties distales de l’intestin grêle. De plus, la survie des EHEC dépend à la fois de lasouche/sérotype étudié et de la matrice alimentaire dans laquelle les bactéries sont ingérées. En conditions coliqueshumaines simulées, les EHEC sont progressivement éliminés du milieu colique et leurs principaux gènes de virulence(stx1 codant la Shiga-toxine 1 et eae codant l’intimine) sont surexprimés dans les heures suivant l’inoculation dupathogène. L’ajout de levures probiotiques du genre Saccharomyces ne modifie pas la survie du pathogène dansl’environnement colique, que celles-ci soient administrées en traitement « curatif » ou « prophylactique ». Parcontre, l’administration de S. cerevisiae CNCM I-3856 permet (i) de moduler favorablement l’activité fermentairedu microbiote intestinal, en augmentant la production d’acétate et en réduisant celle du butyrate et (ii) de diminuersignificativement l’expression de stx1. Par ailleurs, l’effet du pathogène et des probiotiques sur le microbiote coliqueest individu dépendant, confortant l’hypothèse que des facteurs associés à l’hôte, comme le microbiote, pourraientconditionner l’évolution clinique des infections à EHEC et l’efficacité d’une stratégie probiotique. Enfin, dans unmodèle murin d’anses iléales, l’administration préventive de S. cerevisiae CNCM I-3856 limite significativementl’interaction d’O157:H7 avec les plaques de Peyer et les lésions hémorragiques associées.Ces résultats confirment donc l’intérêt d’une stratégie probiotique dans le contrôle des infections à EHEC. Uneétude plus approfondie du transcriptome du pathogène dans l’environnement digestif humain, en présence ou non deprobiotiques, permettrait de mieux comprendre la physiopathologie des infections à EHEC et les mécanismes associés / The enterohaemorrhagic Escherichia coli (EHEC) are zoonotic pathogens that cause food-borne infection withwhich leads to life-threatening damage in humans. EHEC survival and expression of virulence genes in the humandigestive track are key factors in the pathogenesis of these infections, but little is known, mainly due to lack ofappropriate study models. The absence of specific treatment has led to an interest in preventive and/or alternativemeasures healing, such as the use of probiotics. The objective of this study is the behavior of EHEC strains in theentire digestive tract and the influence of probiotic strains, using in vitro and in vivo complementary approaches.In vitro, in the upper gastrointestinal tract, a bacterial mortality was observed in the stomach, followed bya bacterial resumption in the distal segment of the small intestine. Moreover, survival depends on both theEHEC strain/serotype studied and the food matrix in which the bacteria are ingested. In simulated humancolon conditions, EHEC was progressively eliminated from the bioreactor and the major virulence genes (stx1encoding Shiga-toxin 1 and eae encoding intimin) are overexpressed in the hours following the inoculation ofpathogen. Probiotic yeasts Saccharomyces genus does not modify the survival of the pathogen in the in vitro colonicenvironment, that they be administered in treatment "curative" or "prophylactic". Still, the administration ofS. cerevisiae CNCM I-3856 allows (i) to favorably modulate fermentation activity of the intestinal microbiota, byincreasing the production of acetate and reducing that of butyrate and (ii) reduce significantly the expression ofstx1. Furthermore, the effect of pathogenic and probiotic on colonic microbiota is donor-dependent, supporting thehypothesis that factors associated with the host, as the microbiota could condition the clinical course of EHEC andefficiency a probiotic strategy. Finally, in a murine model of ileal loops, preventive administration of S. cerevisiaeCNCM I-3856 significantly limits the interaction of O157:H7 with the Peyer’s patches and results hemorrhagic lesions.These results confirms the interest of probiotic strategy in controlling EHEC infections. Further transcriptomestudies are warranted for the pathogen in the human digestive environment, with or without probiotics for the betterunderstanding of the pathophysiology of EHEC and so on the mechanisms involved in the antagonistic effect ofprobiotics.

Pretendeu-se, no presente estudo, verificar a segurança e a eficácia do transplante de células-tronco derivadas do tecido adiposo (ASC) em ratos com UC induzida por ácido trinitrobenzenosulfonico (TNBS). A população celular foi isolada do tecido adiposo por dissociação mecânica e cultivada. O comportamento celular foi verificado por meio da morfologia, proliferação, viabilidade, capacidade de aderência à superfície plástica e parâmetros de diferenciação osteogênica, condrogênica e adipogênica. Os animais foram avaliados, considerando-se os aspectos clínicos, macroscópicos, microscópicos e bioquímicos. No modelo experimental de UC, a infusão de ASC reduziu significativamente a presença de aderências entre o cólon e órgãos adjacentes, bem como diminuiu a quantidade de células inflamatórias na mucosa lesada. Conclui-se que as ASC podem promover e/ou acelerar o processo de regeneração da mucosa intestinal inflamada e assim, serem empregadas como uma opção terapêutica com amplo potencial de aplicabilidade no tratamento da DII. / It was intended in this study verify the safety and efficacy of the transplantation of adipose derived stem cells (ASC) in rats with ulcerative colitis induced by trinitrobenzenosulfonico acid (TNBS). The cell population was isolated from the adipose tissue by mechanical dissociation and cultured. The cell behavior was verified by the morphology, proliferation, viability, ability to adhere to the plastic surface and parameters of osteogenic differentiation, adipogenic and chondrogenic. The animals were evaluated, considering the aspects clinical, macroscopic, microscopic and biochemical. In experimental ulcerative colitis, infusion of ASC significantly reduced the presence of adhesions between the colon and adjacent organs and decreased the amount of inflammatory cells in the injured mucosa. It is concluded that the ASC can promote and/or accelerate the healing process of the intestinal mucosa inflamed and thus be employed as a therapeutic option with wide potential application in the treatment of IBD.

Les hépatopathies métaboliques regroupent les maladies non alcooliques du foie (NAFLD) et les maladies alcooliques du foie (MAF) causées respectivement par l’obésité ou une consommation excessive d’alcool. Ces pathologies vont de la simple stéatose à des formes aggravées pouvant aller jusqu’au carcinome hépatocellulaire. D’autres facteurs que le surpoids ou l’abus d’alcool jouent un rôle dans la susceptibilité des patients à développer une NAFLD ou une MAF. Cette thèse a pour objectif de clarifier et d'étudier les mécanismes et les facteurs participant à l’installation de l’inflammation dans ces deux pathologies. Mes travaux ont porté d’une part sur le rôle de la cellule de Kupffer dans les étapes précoces de la NAFLD et d’autre part sur l’étude du microbiote intestinal comme cofacteur déclenchant de la MAF. La cellule de Kupffer lors de la stéatose, étape précoce de la NAFLD, présente une dérégulation de son homéostasie lipidique qui participe à son phénotype pro-inflammatoire et favorise l’inflammation hépatique. L’impact du fructose, largement utilisé dans notre alimentation actuelle, a été étudié et aggrave l’inflammation hépatique lors d’un régime hyperlipidique et ceci est associé à une dysbiose spécifique. Dans la MAF, une dysbiose intestinale, une diminution des Bacteroides, a été associée aux lésions hépatiques dans un modèle murin d’alcoolisation. L‘utilisation de traitements permettant de maintenir cette population à des taux élevés a corrigé cette dysbiose et protégé les animaux face aux lésions hépatiques. Ces travaux permettent d‘envisager le MI comme une cible prometteuse permettant de contrôler l’évolution des hépatopathies métaboliques vers des formes sévères. / Metabolic hepatopathies is including Non Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Liver Disease (ALD) due to an excessive consumption of alimentation or alcohol. The pathologies range from simple steatosis to aggravated forms until hepatocellular carcinoma. Other factors than overweight or alcohol abuse play a role in sensitivity of patients to develop NAFLD or ALD. The aim of this thesis is to clarify and study the mechanisms and factors that lead to the installation of inflammation in those pathologies. My work covered in part on the role of Kupffer cell in the early stages of NAFLD and secondly on the study of intestinal microbiota as a cofactor triggering the MAF.The Kupffer cell role in steatosis, the early stages of NAFLD, showed a deregulation of its lipid homeostasis involved in the pro-inflammatory phenotype and promotes liver inflammation. The impact of fructose, widely used in our current diet, was studied and worsening liver inflammation during high fat diet. This is associated with a specific dysbiosis. In ALD, intestinal dysbiosis, a decrease of Bacteroides, leading to liver damage has been established. The use of treatments to maintain this population with high levels corrected the dysbiosis and has protected animals against liver damages. Both works on the NAFLD and ALD establish MI is a promising target to control the evolution of metabolic liver diseases toward aggravated forms.