Orientador: Elizeu Antonio Rossi / Coorientador: Daniela Cardoso Umbelino Cavallini / Banca: Marla Simone Jovenasso Manzoni / Banca: Regina Celia Vendramini / Resumo: O presente trabalho avaliou os efeitos do simbiótico fermentado com Enterococcus faecium CRL 183 e Lactobacillus helveticus ssp jugurti 416, à base de extratos de soja e de yacon produzidos em ratos com Diabetes mellitus, cuja indução foi feita quimicamente pela administração intraperitoneal de estreptozotocina (50mg/kg de peso corporal). Os animais foram divididos em quatro grupos experimentais (n=10): I - animais não diabéticos que receberam somente ração (controle negativo); II - animais diabéticos que receberam somente ração (controle positivo); III - animais diabéticos que receberam ração + dose de 1 mL/Kg de peso corpóreo/dia do produto não fermentado a base de soja e yacon; IV - animais diabéticos que receberam ração + dose de 1 mL/Kg de peso corpóreo/dia do produto fermentado a base de soja e yacon. No produto em estudo foram quantificadas a viabilidade dos microrganismos probióticos e a concentração dos frutanos (FOS e inulina). O período experimental foi de 59 dias e os parâmetros avaliados foram: peso corpóreo dos animais, ingestão hídrica e alimentar, Coeficiente de Eficácia Alimentar (CEA), glicemia, enzimas aspartato aminotransferase (AST) e alanina aminotransferase (ALT), triglicerídeos, colesterol, HDL, nHDL-C, gorduras epididimal e retoperitonial, músculos sóleo e extensor longo dos dedos, cortes histológicos de fígado, pâncreas e rim e, análise de biomarcadores de estresse oxidativo, TBARS (substâncias reativas ao ácido tiobarbitúrico) e DPPH (2,2 - difenil-1-picril de hidrazila). Não foi observada diferença entre os grupos que receberam os produtos não fermentado e fermentado quando comparado com o grupo de diabéticos que não recebeu tratamento, para consumo de água, ração e peso corporal. O mesmo foi observado para os parâmetros bioquímicos, exceto ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study evaluated the hypoglycemic effects of synbiotic fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus ssp jugurti 416, based on soymilk and yacon produced in rats with Diabetes mellitus, whose induction was done chemically by intraperitoneal administration of streptozotocin (50 mg/kg body weight). The rats were divided into four groups (n=10): I - non diabetic animals that received only chow diet (negative control), II - diabetic animals that received only chow diet (positive control), III - diabetic animals that received chow diet + 1mL/kg body weight/day of unfermented product of soybean and yacon, IV - diabetic rats that received chow diet + 1mL/kg body weight/day of fermented product of soybean and yacon extracts. In the product under study were quantification viability of microorganisms of the probiotic and the concentration of fructans (inulin and FOS). The experiment was carried out for 59 days and the parameters were evaluated: body weight of animals, feed and water intake, Food Efficiency Ratio (FER), glucose, enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), levels of triglyceride, cholesterol, HDL-C nHDL, epididymal and retoperitonial white adipose tissue, soleus and extensor digitorum longus and tissues liver, kidney and pancreas, and analysis of biomarkers of oxidative stress, TBARS (thiobarbituric acid reactive substances) and DPPH (2,2 - diphenyl-1-picryl of hidrazila). No difference was observed between the groups that received unfermented and fermented products when compared to the diabetic group that not received treatment, for drinking water, feed intake and body weight. The same was observed for the biochemical parameters, except for fractions HDL-cholesterol and triglycerides. With respect to biomarkers there was... (Complete abstract click electronic access below) / Mestre

Orientador: Antonio Olavo Cardoso Jorge / Co-orientador: Mariella Vieira Pereira Leão / Banca: Juliana Campos Junqueira / Banca: Aguinaldo Silva Garcez Segundo / Resumo: A alta incidência de candidoses causadas por Candida albicans e a capacidade de adaptação desta espécie, assim como resistência aos antifúngicos impulsionam o desenvolvimento de pesquisas com terapias alternativas para controle dessa infecção. O objetivo desse trabalho foi avaliar a influência de Lactobacillus rhamnosus e produtos do seu metabolismo contra C. albicans, avaliando-se a patogenicidade e a expressão de genes que regulam a formação do biofilme de C. albicans, in vitro e in vivo em modelo invertebrado de Galleria mellonella. Foram utilizadas cepas de C. albicans ATCC 18804 e L. rhamnosus ATCC 9595 (provenientes do Laboratório de Microbiologia do Instituto de Ciências e Tecnologia de São José dos Campos / UNESP). Para o estudo foram preparadas duas suspensões de L. rhamnosus, uma contendo a porção celular e a outra com o sobrenadante da cultura, livre de células. O estudo da patogenicidade in vitro de C. albicans foi avaliado pelos testes de formação de biofilme e quantificação de UFC/mL de C. albicans, análise da atividade metabólica pelo método do XTT e filamentação de C. albicans. A análise da curva de sobrevivência de Galleria mellonella foi utilizada para a avaliação in vivo da influência de L. rhamnosus na infecção causada por C. albicans. Os genes, BCR1, EFG1, CPH1, HWP1, ALS1 e ALS3 de C. albicans foram quantificados pela RT-PCR após a interação em modelo de biofilme. No estudo in vitro L. rhamnosus foi capaz de inibir a formação do biofilme, filamentação e reduzir a atividade metabólica de C. albicans. Esses efeitos também foram observados quando utilizado a suspensão do sobrenadante da cultura de L. rhamnosus, apontando possível produção de substâncias com efeito inibitório. Os resultados obtidos in vivo apontam que L. rhamnosus e seu sobrenadante protegeram G. mellonella da infecção por C. albicans, porém a suspensão do sobrenadante apresentou melhores resultados, visto.... / Abstract: The high incidence of candidiasis caused by Candida albicans and the adaptability of this species, as well as resistance to antifungal drive the development of research on alternative therapies to control this infection. The aim of this study was to evaluate the influence of Lactobacillus rhamnosus and products of their metabolism against C. albicans, evaluating the pathogenicity and the expression of genes that regulate the formation of C. albicans biofilms in vitro and in vivo in invertebrate model Galleria mellonella. Strains of C. albicans ATCC 18804 and L. rhamnosus ATCC 9595 were used (from the Microbiology Laboratory of the Institute of Science and Technology of São José dos Campos / UNESP). For the study were prepared from L. rhamnosus two suspensions, one containing the serving cell and the other with the culture supernatant free cells. The study of in vitro pathogenicity of C. albicans was assessed by biofilm formation testing and quantitation of CFU / ml of C. albicans, analysis of metabolic activity by XTT method and C. albicans filamentation. The analysis of the Galleria mellonella survival curve was used to evaluate in vivo the influence of L. rhamnosus in infection caused by C. albicans. Genes, BCR1, EFG1, CPH1, HWP1, ALS1 and ALS3 of C. albicans were quantified by RT-PCR after interacting in biofilm model. In vitro evaluation L. rhamnosus was able to inhibit biofilm formation, filamentation and reduce the metabolic activity of C. albicans. These effects were also observed when using the suspension culture supernatant of L. rhamnosus, indicating the possible of production substances with inhibiting effect. The results obtained in vivo indicate that L. rhamnosus and its supernatant protected G. mellonella of C. albicans infection, but the suspension of the supernatant showed better results, as it increased the survival caterpillar G. mellonella. The results of gene expression have shown that .... / Mestre

Orientador: Daniela Cardoso Umbelino Cavallini / Banca: Patricia de Oliveira Prada / Banca: Marla Simone Jovenasso Manzoni / Resumo: Objetivos: A utilização de microrganismos probióticos na redução do risco de doenças inflamatórias intestinais (DIIs), incluindo a colite ulcerativa (CU), tem se mostrado promissora, sendo que o efeito benéfico depende da cepa utilizada e da fase da patologia. O objetivo do presente estudo foi averiguar o efeito de um produto probiótico à base de soja, fermentado com Enterococcus faecium CRL 183 e Lactobacillus helveticus 416 e com adição de Bifidobacterium longum ATCC 15707, na fase aguda da colite quimicamente induzida em camundongos. Métodos: O protocolo experimental teve duração total de 14 dias e os animais foram distribuídos aleatoriamente em quatro grupos (n=10): Grupo C - Animais sadios que não receberam os produtos em estudo; Grupo CL - Animais com colite quimicamente induzida e que não receberam os produtos em estudo; Grupo CLF - Animais com colite quimicamente induzida e que receberam o produto fermentado probiótico; Grupo CLP - Animais com colite quimicamente induzida e que receberam o produto não fermentado (placebo). A indução da colite foi feita pela administração de dextran sulfato de sódio (DSS) a 3% dissolvido na água fornecida diariamente aos animais, por um período de sete dias, e os produtos foram administrados ao longo dos 14 dias de estudo. Durante o período experimental foram monitorados os seguintes parâmetros: peso corpóreo dos animais, ingestão hídrica e de ração, consistência e presença de sangue oculto ou aparente nas fezes e composição da microbiota fecal. Ao final do protocolo, os animais foram eutanasiados e o intestino grosso foi removido para realização das análises macroscópica e histológica. Resultados: De acordo com os resultados do índice de atividade da doença (IAD), os animais que consumiram o produto probiótico (CLF) apresentaram redução dos sintomas associados à colite durante... / Abstract: Objectives: The use of probiotic microorganisms in the reduction of inflammatory bowel diseases (IBD) risks, including ulcerative colitis (UC), has been shown promising, and the beneficial effect depends on the strain used and the stage of disease. The objective of this study was to investigate the effect of a probiotic soy product fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 with addition of Bifidobacterium longum ATCC 15707 in the acute phase of colitis chemically induced in mice. Methods: The experimental protocol had total duration of 14 days and the animals were randomized into four groups (n = 10): Group C - healthy animals that have not received the products under study; CL Group - Animals with chemically induced colitis and who have not received the products under study; CLF Group - Animals with chemically induced colitis and receiving the probiotic fermented product; Group CLP - animals with chemically induced colitis and receiving the unfermented product (placebo). The induction of colitis was made by the administration of dextran sodium sulfate (DSS) 3% dissolved in the drinking water for a period of seven days, and the products were administered over the 14 days of the study. During the trial period the following parameters were monitored: body weight, water and food intake, consistency and presence of hidden or apparent blood in stool and composition of the fecal microbiota. At the end of the protocol, the animals were euthanized and the large intestine was removed to perform the macroscopic and histological analysis. Results: According to the results of disease activity index (DAI), the animals that consumed the probiotic product (CLF) showed a reduction of symptoms associated with colitis during the induction period, compared to the ... / Mestre

A procura por suplementos alimentares cresce a cada ano, pois o seu uso contínuo promove a melhora e manutenção da qualidade de vida do hospedeiro. Sustentado neste princípio, a ingestão de produtos probióticos, principalmente leites fermentados, passa a ser uma alternativa neste segmento do mercado. Os probióticos são suplementos alimentares que contem microrganismos vivos que trazem benefícios à saúde do consumidor pela manutenção e melhora do balanço microbiano do trato gastrintestinal. Existem vários gêneros de microrganismos que apresentam propriedades probióticas, destacando-se o gênero Lactobacillus; que exercem várias funções benéficas ao hospedeiro como a diminuição dos níveis de colesterol sangüíneo, efeito anticarcinogênico, adesão ao epitélio intestinal, melhora do sistema imune e a exclusão competitiva, conhecida também como efeito barreira. Dentro deste contexto, o presente trabalho teve como objetivo avaliar o efeito de inibição exercido por cinco cepas de Lactobacillus isoladas de fezes humanas: denominadas L. plantrum (Lac-01), L. plantarum (Lac-02), L. fermentum (Lac-03), L. fermentum (Lac-04) e L. fermentum (Lac-05) sobre o crescimento de E. coli O157:H7, Listeria spp., P. aeruginosa ATCC 27853, Salmonella typhi e Shigella spp , por meio da técnica de co-cultura. Os resultados revelaram que as cepas Lac-01, Lac-02 e Lac-03 foram capazes de inibir, em diferentes níveis, o crescimento das cepas patogênicas avaliadas, sendo este efeito mais acentuado para S. typhi e Shigella spp. Observou-se ainda que a cepa Lac-04 não apresentou efeito de inibição sobre E. coli O157:H7 e P. aeruginosa, ao passo que a cepa Lac-05 inibiu o crescimento de P. aeruginosa, S. typhi e Shigella spp., sendo incapaz de inibir E. coli O157:H7 e Listeria spp, nas condições estudadas. Posteriormente ao se verificar a produção de substâncias antimicrobianas por meio do método \"spot-test\", observou-se o efeito positivo de inibição exercida pelas cepas de Lactobacillus sobre o crescimento dos respectivos patógenos. Verificou-se também, por meio de testes enzimáticos específicos, que as substâncias antimicrobianas produzidas pelas cepas de Lactobacillus não foram sensíveis às enzimas utilizadas, não podendo afirmar, desta forma, que estas substâncias são bacteriocinas. Os testes de co-agregação demonstraram que as cepas Lac-04 e Lac-05 exerceram melhor efeito sobre os patógenos, quando comparadas com as cepas Lac-01 e Lac-02. A cepa Lac-03 não exerceu efeito de coagregação com nenhum dos patógenos avaliados. Os testes de autoagregação revelaram que as cepas Lac-01, Lac-02, Lac-04 e Lac-05 exerceram efeito de autoagregação acentuado. Observou-se ainda que nenhum dos patógenos estudados foi capaz de autoagregar. / The probiotics are special food that contain live microorganisms that promote beneficits to consumer health through maintenance and improvement of microbial balance of gut tract. There are many microorganisms species used in probiotics products, standing out Lactobacillus species that produce many beneficies to consumer like decrease of blood cholesterol level, anti-carcinogenic effect, adhrence to intestinal epithelium, immune system stimulation and the competitive exclusion, also known as barrier effect. In this regard, the present work aimed to evaluate the inhibition effect exerted by five Lactobacillus strains, isolated from humam faeces: denominate, L. plantarum Lac-01, L. plantarum Lac-02, L. fermentum Lac-03, L. fermentum Lac-04 e L. fermentum Lac-05 on the gowth of E. coli O157:H7, Listeria spp., Pseudomonas aeruginosa ATCC 27853, Salmonella typhi and Shigella spp., by means of coculture technique. The results showed that the strains Lac-01, Lac-02 and Lac-03, were able to inhibit, at different levels, the growth of pathogenic strains, and this effect was more accentuated on S. typhi and Shigella spp. It was also observed that the strain Lac-04 did not present inhibition effect on E. coli O157:H7 and P. aeruginosa ATCC 27853, and the Lac-05 inhibited the growth of P. aeruginosa, S. tyhpi and Shigella spp., and showed no effect on E. coli O157:H7 and Listeria spp. Afterwards, the production of antimicrobial substance was verified by means of \"spot-test\" method, showing the positive inhibition effect exerted by all Lactobacillus strains on the growth of the respective pathogens. By means of specific enzymatic test, the antimicrobial substances produced by lactobacillus strains were not sensible to the action of enzymes proteinase-K, papain and pepsin, but this is not enough to affirm that this substances are bacteriocins. The coaggregation test demonstrated that the strains Lac-04 and Lac-05 exerted better effect on the pathogens, when compared to strains Lac-01 and Lac-02. The strain Lac-03 did not coaggregate with any pathogenic strains. The autoaggregation test showed that the strain Lac-01, Lac-02, Lac-04 and Lac-05 exerted accentuated auto-aggregation effect. The studied pathogen was not able to autoaggregate.

Orientadores: José de Assis Fonseca Faria, Adriano Gomes da Cruz / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-26T06:58:49Z (GMT). No. of bitstreams: 1 Pereira_ElienePenhaRodrigues_D.pdf: 2140514 bytes, checksum: 2b677d12d3d80a44118988e2a44c9770 (MD5) Previous issue date: 2014 / Resumo: O estresse oxidativo das bactérias probióticas representa uma grande preocupação para a indústria de alimentos probióticos, pois a presença de oxigênio pode levar tais bactérias à morte em poucos dias fazendo com que o produto deixe de apresentar suas propriedades funcionais alegadas. Assim, estudos são cada vez mais necessários para prolongar a vida de prateleira dos produtos probióticos. Nesse sentido foi avaliado o potencial do extrato da casca de jabuticaba, obtido por extração com fluido supercrítico, como fonte natural de antioxidantes, que além de promover a redução do estresse oxidativo das bactérias probióticas, também pode trazer benefícios à saúde. O extrato de jabuticaba foi bastante eficiente na manutenção da contagem das culturas de Lactobacillus acidophilus e Bifidobacterium lactis no Petit Suisse ao longo de 28 dias de estocagem refrigerada. O Petit Suisse acrescido do extrato também apresentou menor valor de pH final e maior produção de ácidos orgânicos o que pode estar relacionado com a maior atividade antioxidante do extrato em relação aos demais antioxidantes estudados, ácido ascórbico, cisteína e glicose oxidase, o que favorece o metabolismo das culturas probióticas. O Petit Suisse com o extrato também apresentou boa aceitação por possíveis consumidores do produto, obtendo elevada intenção de compra / Abstract: The oxidative stress of the probiotic bacteria represents a great preoccupation for the probiotics food products, since the presence of oxygen may cause bacteria death in a few days making that the product don't present the functional properties cited. Thus, studies are each more necessaries to improve the shelf life of the probiotic products. Then it was evaluated the potential of the jaboticaba peel supercritical fluid extract, a natural source of antioxidants, that promotes the reduction of the oxidative stress of the probiotic bacteria, and also achieving health benefits. The jaboticaba peel was very efficient on the maintenance of the counts of the cultures of Lactobacillus acidophilus and Bifidobacterium lactis on Petit Suisse during 28 days of storage. The Petit Suisse added of the extract also presents lowest value of final pH and greatest production of organic acids which may be related with the greatest antioxidant activity of the extract in comparison with the others antioxidants studied, ascorbic acid, cistein and glucose oxidase, what favors the probiotic cultures metabolism. The Petit Suisse containing extract also present good acceptability between the potential consumers of the product, obtaining great purchase intent / Doutorado / Tecnologia de Alimentos / Doutora em Tecnologia de Alimentos

The project was undertaken to establish the normal intestinal flora of healthy cheetahs and to produce a species-specific probiotic for use in juvenile cheetahs in captivity to improve weight gain and reduce diarrhoea. The normal intestinal flora of healthy cheetahs was established using non-selective and selective media. High numbers of anaerobic bacteria and aerobic bacteria were isolated from the faeces of cheetahs in this study. Eight percent of isolates were Enterococcus spp. Both Enterococcus faecium and Lactobacillus Group 1 were selected for use in the probiotic. Twenty-seven juvenile cheetahs between eight and thirteen months of age were included in the probiotic trial (Median: 12 months). The probiotic was fed for 28 days to the Probiotic Group. Both the Probiotic and Control groups were monitored for 70 days prior to the administration of the probiotic and 14 days after administration. The feeding of the cheetah-specific probiotic resulted in an increase of weight in the treatment group (p=0.026, ANOVA, p<0.05) in comparison to the Control Group. There was a relative improvement in the faecal quality in the Probiotic Group in comparison to the Control Group. This was accompanied by an absence of blood and mucus in the faeces, which had been present prior to the start of the 28-day administration of the probiotic. The feeding of a cheetah-specific probiotic resulted in an improved weight gain and food conversion in the Probiotic Group in comparison to the Control Group as well as in a reduction of diarrhoea in the Probiotic Group. More research is needed on the effect of the probiotic on different age groups and animals suffering from specific diseases such as liver disease and gastritis. / Dissertation (MSc (Veterinary Science))--University of Pretoria, 2004. / Veterinary Tropical Diseases / unrestricted

Tesis por compendio / [EN] Celiac disease (CD) is a chronic enteropathy triggered by cereal gluten proteins in genetically predisposed individuals. The etiology is strongly associated with the genes of the human leukocyte antigen (HLA) encoding the DQ2/DQ8 molecules. Most CD patients carry this genotype but this is also present in the 40% of the general population and only a small percentage develops the disease. Thus, the HLA-DQ genotype is necessary but not solely responsible for the disease development. Gluten is the main environmental trigger but its intake neither fully explains the onset nor its clinical manifestations. Other environmental factors (e.g. early feeding practices, infections, intestinal microbiota) have been associated with the risk of developing CD. The only treatment for CD patients is the adherence to a gluten free diet (GFD), but the compliance with this dietary strategy is complicated because gluten is present in many foods. Therefore, the identification of modifiable environmental factors that contribute to CD onset is critical for the development of strategies to reduce its incidence. Observational studies in CD patients revealed imbalances in the intestinal microbiota which could contribute to the pathogenesis of the disease. It has been proposed that these imbalances are not only a secondary consequence of the disease but could also be a predisposing factor. To understand whether gut microbiota imbalances play a role in CD onset and pathogenesis, in vitro, animal and human prospective and intervention studies have been conducted in the context of the present PhD Thesis. The global aim of this Thesis has been to improve the understanding of the role played by intestinal microbiota in the pathogenesis and risk of CD, and the possibilities of contributing to disease prevention and treatment by modulating gut microbiota composition. Chapter 1 includes two in vitro studies investigating the influence of components of the gut microbiota (bifidobacteria and enterobacteria) on the maturation and functions of immunocompetent cells (dendritic cells), and on gluten toxicity in the intestinal epithelium (Caco-2 cells). We have observed that some Bifidobacterium strains are able to reduce the activation of dendritic cells and ameliorate the toxicity of gluten on intestinal epithelial cells. In Chapter 2 the effects of the administration of Bifidobacterium longum CECT 7347 was evaluated in an in vivo model of gluten induced enteropathy in newborn rats, resulting in a reduced proinflammatory cytokine production in the small intestine and CD4+T cell numbers in peripheral blood. Chapter 3 includes two observational studies in humans to unravel whether breast-feeding and human milk composition and/or the host genotype (HLA-DQ) are related to the microbiota, thereby influencing the later development of CD. We concluded that both factors may contribute to the early intestinal colonization of the infant's gut, influencing the Bifidobacterium spp. numbers. Human milk composition also varies in CD and non-CD mothers, modifying the supply of bifidobacteria and protective immune factors to the offspring. Finally, in Chapter 4 we have studied the potential beneficial effects of the administration of B. longum CECT 7347 in addition to the GFD to children with newly diagnosed CD. This study demonstrates that the bifidobacteria slightly reduces serum inflammatory markers and restored the gut microbiota composition. / [ES] La enfermedad celíaca (EC) es una enteropatía crónica de carácter autoinmune que sufren individuos genéticamente predispuestos tras la ingesta de gluten. La etiología está asociada con los genes del sistema "Antígeno Leucocitario Humano" (HLA) que codifican las moléculas DQ2/DQ8. Los pacientes con EC presentan este genotipo, sin embargo este también está presente en ¿40% de la población general y sólo un pequeño porcentaje desarrolla la enfermedad. Por lo tanto, el genotipo HLA-DQ resulta necesario pero no suficiente para que se desarrolle la enfermedad. El gluten es el principal desencadenante pero su ingesta tampoco explica su desarrollo ni sus manifestaciones clínicas. Otros factores ambientales (p.e. la lactancia, infecciones, microbiota intestinal) se han asociado con el riesgo de desarrollar la EC. El único tratamiento para los pacientes celíacos es el seguimiento de una dieta exenta de gluten (DEG), sin embargo su cumplimiento es complicado debido a que el gluten está presente en la mayoría de los alimentos procesados. Por ello, la identificación de factores ambientales modificables que contribuyan al desarrollo de la enfermedad, resulta fundamental para desarrollar estrategias que permitan reducir su incidencia. Estudios observacionales realizados en pacientes con la EC, han demostrado la existencia de desequilibrios en su microbiota intestinal, que podrían contribuir a la patogénesis de la enfermedad. Se ha propuesto que estos desequilibrios no son sólo una consecuencia secundaria de la EC, sino que podrían ser un factor predisponente. Para entender si la microbiota está implicada en el desarrollo y patogénesis de la EC, en la presente Tesis se han desarrollado estudios in vitro, con animales y estudios prospectivos y de intervención en humanos. El objetivo de esta Tesis ha sido avanzar en el conocimiento de la función que la microbiota intestinal desempeña en la patogénesis de la EC, así como, acerca de las posibilidades de tratar o prevenir esta enfermedad mediante la modulación de la composición de la microbiota intestinal. El Capítulo 1 incluye dos estudios in vitro en los que se ha estudiado la influencia de componentes de la microbiota intestinal (bifidobacterias y enterobacterias) en la maduración y las funciones de células inmunocompetentes (células dendríticas), y en la toxicidad del gluten en el epitelio intestinal (células Caco-2). Hemos observado que algunas cepas de Bifidobacterium son capaces de reducir la activación de las células dendríticas y de reducir la toxicidad del gluten sobre el epitelio intestinal. En Capítulo 2 incluye el estudio de los efectos de la administración de B. longum CECT 7347 en un modelo de enteropatía inducida por gluten en ratas recién nacidas, observándose una reducción de citoquinas proinflamatorias en el intestino y de células T CD4+ en sangre periférica. El Capítulo 3 incluye dos estudios observaciones en humanos en los que se ha investigado si la lactancia y composición de la leche materna y/o el genotipo (HLA-DQ) están relacionados con la microbiota y, si así, podrían influir en el desarrollo de la EC. Concluimos que ambos factores contribuyen a la colonización intestinal del niño en los primeros meses de vida, afectando especialmente al número de Bifidobacterium spp. La composición de la leche maternal varía entre madres celíacas y sanas, lo que podría modificar el aporte de bifidobacterias y factores inmunológicos protectores al lactante. Por último, en el Capítulo 4 incluye el estudio del potencial efecto beneficioso de la administración de B. longum CECT 7347 junto con la DEG en niños recién diagnosticados de EC. Este estudio demuestra que la bifidobacteria ligeramente reduce los marcadores inflamatorios en sangre periférica y contribuye a restablecer la composición de la microbiota intestinal. / [CA] La malaltia celíaca (MC) és una enteropatia crònica provocada per les proteines del gluten de cereals en individus predisposats genèticament. L'etiologia està fortament associat amb els gens de l'antigen leucocitari humà (HLA). Pacients amb MC porten aquest genotip però també està present en aproximadament el 40% de la població general i només un petit percentatge (1-3%) es desenvolupa la malaltia. Per tant, HLA-DQ genotip és necessària, però no l'únic responsable. El gluten és el principal desencadenant ambiental però la seva ingesta no explica completament l'inici ni les seves manifestacions clíniques. Altres factors ambientals, com la microbiota intestinal, s'han associat amb el risc de desenvolupar CD. Els estudis observacionals en pacients amb MC van revelar desequilibris en la microbiota intestinal que podria contribuir a la patogènesi de la malaltia. S'ha proposat que aquests desequilibris no només són una conseqüència secundària de la malaltia, però també podria ser un factor predisponent. Per entendre si els desequilibris microbiota intestinal podrien tenir un paper en l'aparició de CD, un estudi prospectiu amb el nen en risc la família està en marxa. L'únic tractament per als pacients amb EC és l'adherència a una dieta lliure de gluten, però el seu compliment és complicada a causa del gluten està present en molts aliments. La identificació de factors ambientals modificables que contribueixen a l'aparició de CD és fonamental per a les estratègies de desenvolupament que porten a una reducció de la incidència. Aquest pot ser el cas per als components de la microbiota intestinal, l'adquisició podria ser modulada per factors ambientals i dietètics. L'objectiu global de la tesi és desentranyar els coneixements actuals sobre el paper exercit per la microbiota intestinal en la patogènesi de l'EC, i les possibilitats de contribuir a la prevenció i tractament de la malaltia mitjançant la modulació de la composició de la microbiota intestinal En el Capítol 1 hem estudiat l'ús de models in vitro de la influència de la microbiota intestinal durant la maduració i funcions del sistema immunològic (cèl·lules dendrítiques), i les interaccions entre el gluten i intestinal intestí i la resposta de l'epiteli intestinal resultant d'aquesta interacció. Hem observat que alguns ceps de Bifidobacterium són capaços de reduir l'activació del sistema immune i millorar la resposta nociva de l'epiteli intestinal a l'estimulació amb gluten. En el Capítol 2 hem estudiat els efectes de l'administració d'una soca de Bifidobacterium (B. longum CECT 7347) per a un model animal de rates nounades. El tractament amb els bacteris es va associar amb una reducció en la producció de citocines proinflamatòries i la resposta immune de cèl·lules T CD4 +. En el Capítol 3 es va descriure que alguns genètic (HLA-DQ genotip) i factors ambientals (llet materna) influeixen en la colonització intestinal primerenca, especialment en Bifidobacterium spp., que poden influir en l'aparició de CD més tard. Finalment, en el Capítol 4 s'ha estudiat l'efecte probiòtic de l'administració de B. longum CECT 7347 en nens acabats diagnosticats d'EC i el seu paper en el restabliment de la salut intestinal. / Olivares Sevilla, M. (2015). Influence of intestinal microbiota in celiac disease pathogenesis and risk [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/58768 / TESIS / Premios Extraordinarios de tesis doctorales / Compendio

There is an increasing interest in how therapeutic drugs could alter the human gut microbiota composition and function. While some knowledge is accumulating on the antimicrobial impact of some psychotropics on isolated strains or the gut microbiota of animal models, information about other classes of psychotropics and representative species from the human gut is poorly investigated. The antimicrobial effect of psychotropic drugs is usually neglected as a confounding factor when investigating gut microbiome biomarkers, knowing that patients are generally put in long-term medication. The purpose of the present study was to investigate (in vitro and ex-vivo) the antimicrobial activity of some oral commonly prescribed psychotropics from different therapeutic classes on colonic microbiota diversity and metabolism and the potential capacity of probiotics to alleviate related dysbiosis. The findings of this study revealed an important in vitro inhibitory activity of psychotropic drugs, which were also expressed as drastic alterations in gut microbiota composition ex-vivo. Indeed, the relative abundances of Firmicutes and Actinobacteria were lowered while the Proteobacteria population was increased. Families of Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also declined by psychotropics (aripiprazole) treatment. These microbial changes were translated into a decrease of the major SCFA (butyrate, acetate, and propionate) at the metabolic level. The addition of a probiotic combination (Lactobacillus rhamnosus and Bifidobacterium longum) concomitantly with a psychotropic (aripiprazole) had a protective effect by attenuating the decline of microbiota composition and increasing the concentrations of SCFA. These findings provide evidence that psychotropics, through their antimicrobial effect, have the potential to alter the human gut microbiota composition and metabolism, while probiotics can mitigate the related dysbiosis.

Recent research has highlighted the connection between dysbiosis of the gut microbiome and its role in the development of Irritable Bowel Syndrome (IBS). Over the last few years, probiotics have grown in popularity as a potential treatment option in IBS. However, most current probiotic studies are limited due to small study populations, older median age, and short study time duration. The proposed study will be a multicenter, randomized, double-blinded placebo controlled study comparing the multi-strain probiotic Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Escherichia coli DSM17252 to placebo in patients diagnosed with IBS based on Rome IV criteria over a 3-months duration. The study participants will have a baseline evaluation and a final evaluation at the end of the 3-months duration. The primary outcome will be the IBS Symptom Severity Score and the secondary outcomes will the individual components of the IBS Symptom Severity Score. The results of this study will begin to fill gaps in the current knowledge of the use of probiotics in the treatment of IBS.

Lactic acid producing bacteria (LAB) and organic acids have been proposed as effective alternatives to antibiotics, however there is limited literature concerning their combination. Thus, the objective of this thesis was to investigate the effects of LAB, encapsulated butyric acid (EBA), and their combination. Under challenged conditions, the in vitro study demonstrated that both EBA and LAB were capable of reducing pathogen proliferation over time, with greater efficacy at lower initial concentration. However, EBA demonstrated a greater effectiveness on pathogen reduction. Under challenged conditions, the results of the in vivo study indicated that birds fed LAB performed comparatively to that of birds fed antibiotics concerning BW and FCR from d 0-45 and both diets enhanced gut physiology, pH and immune parameters. Overall, the results of the thesis indicate the ineffectiveness of combining EBA and LAB, while providing valuable evidence supporting LAB as an effective alternative to antibiotics.