This dissertation project aimed to demonstrate that pulmonary delivery of two anorectic gut secreted peptides, peptide YY (PYY) and oxyntomodulin (OXM) enabled food intake suppression and reduced body weight gain in rats via their systemic absorption from the lung and interaction with the brain. After PYY and OXM were administered to the lungs at varying doses, food intake and body weight gain were monitored in freely feeding rats. Significant 30-35 % food intake suppression was achieved for 4-6 h following pulmonary administration of endogenously active PYY3-36 and OXM1-37 at 0.80 and 0.50 mg/kg, respectively. Moreover, when administered daily for 7 days, these peptides enabled significant reduction of body weight gain by 39.4 and 62.3 %, respectively. However, neither of their active fragment peptides, PYY13-36, OXM30-37 and NAc-OXM30-37 was effective at doses equimolar to the effective doses of PYY3-36 and OXM1-37. For PYY3-36, its pulmonary administration caused c-Fos activation in the hypothalamus arcuate nucleus (ARC) only, which was concurrent to reduced orexigenic neuropeptide Y (NPY), suggesting its appetite suppression was mediated via the central nervous system (CNS). In contrast, OXM1-37 caused c-Fos activation in both the hypothalamus ARC and brainstem AP, which implied the involvement of the CNS control and vagal stimulation for this peptide. As it was clear that these effects resulted from their lung absorption and increased plasma levels, the pharmacokinetics of one of the peptides, PYY3-36 was characterized following pulmonary administration. The plasma profiles were dose-proportional and kinetically, non “flip-flop”, yielding the highest PYY3-36 concentrations (Cmax) of 75.0±9.3 and 726.3±69.0 ng/ml at 0.08 and 0.80 mg/kg, respectively, at 10 min. According to a new kinetic model developed in this project, the percent absolute bioavailability (% F) was estimated to be 12-14 %, as derived from the lung absorption (ka) and non-absorptive loss rate constant (knal) of 0.03 min-1 and 0.17-0.22 min-1, respectively. Overall, this research provided the first proof-of-concept for effective appetite suppression with pulmonary delivery of anorectic gut secreted peptides via systemic absorption.

It is well established that replacing dietary saturated fatty acids with unsaturated fatty acids reduces cardiovascular disease (CVD) risk. Although epidemiological and clinical evidence indicate health benefits of consuming various fatty acid classes including n-9, n-6, and short- and longer-chain n-3 fatty acids, current dietary recommendations fall short of providing the optimal amounts of these fatty acids in daily diets. In addition, significant knowledge gaps remain in our understanding of the effects of, and mechanisms underpinning the action of, the various fatty acid classes on risk factors for CVD. The objective of this research was to contribute to the evaluation of health benefits of using different dietary oils, and determine how these benefits may play a role in improving public health and decreasing CVD risk. Additionally, this research examined effects of diet-gene interactions, endogenous fatty acid ethanolamides (FAEs) on body fat mass distribution as well as changes in the composition of gut microbiota following consumption of dietary oil treatments. The Canola Oil Multicenter Intervention Trial (COMIT) was conducted as a 5-phase randomized, controlled, double-blind, cross-over clinical trial. Each 4-wk treatment period was separated by 4-wk washout intervals. A total of 130 volunteers with abdominal obesity consumed each of 5 identical weight-maintaining, fixed-composition diets with one of the following treatment oils (60 g/3000 kcal) in the form of beverages: 1) conventional canola oil (Canola; n-9 rich), 2) high–oleic acid canola oil with docosahexaenoic acid (CanolaDHA; n-9 and n-3 rich), 3) a blend of corn and safflower oil (25:75) (CornSaff; n-6 rich), 4) a blend of flax and safflower oils (60:40) (FlaxSaff; n-6 and short-chain n-3 rich), and 5) high–oleic acid canola oil (CanolaOleic; highest in n-9). At endpoints, plasma fatty acid levels reflected the differences in fatty acid composition of five dietary treatments. All diets lowered total cholesterol (TC) compared with baseline. TC was lowest after the FlaxSaff phase and highest after CanolaDHA. The CanolaDHA treatment improved HDL-C, triglycerides, and blood pressure thereby reducing Framingham risk scores compared with other oils varying in unsaturated fatty acid composition. Homozygotes minor allele carriers of rs174583 (TT) on FADS2 gene showed lower (P<0.01) plasma EPA and DPA levels across all diets, but no differences were observed in DHA concentrations after the CanolaDHA feeding. In addition, plasma FAE levels were positively associated with plasma fatty acid profiles. Minor allele A carriers of rs324420 of FAAH gene showed a higher (P<0.05) plasma FAE levels compared with major allele C carriers across all diets, and showed higher (P=0.0002) docosahexaenoylethanolamide levels in response to the CanolaDHA diet. Impacts of consuming 60 g of five dietary oil treatments on gut microbiota composition were relatively minor at the phylum level and mainly at the genus level, while BMI contributed to a significant shift at the phylum level. In conclusion, consumption of a novel DHA-enriched canola oil improved blood lipid profile and largely reduced CVD risk. Diet-gene interactions might help identify sub-populations who appear to benefit from increased consumption of DHA and oleic acid. The metabolic and physiological responses to dietary fatty acids may be influenced via circulating FAEs, while the altered microbiota profile by shifts in MUFA and/or PUFA may be associated with specific physiological effect. Personalized diets varying in unsaturated fatty acids composition based on specific lifestyles, environmental factors, psychosocial factors, and genetic make-ups will become the future “healthy eating” recommendations to prevent CVD risk. / May 2016

A microbiota intestinal (MI) é formada por milhões de microrganismos presentes no trato gastrointestinal, especialmente no cólon. Recentemente, estudos tem sugerido que o treinamento físico aeróbio pode modificar a composição desta MI, por exemplo, aumentando a abundância de bactérias comensais, as quais positivamente influenciam o organismo do hospedeiro. Entretanto, algumas lacunas existem: estudos foram realizados majoritariamente em animais e estes apresentaram associação com outros modelos de dietas e doenças; em humanos, estudos observacionais não apontaram causalidade do treinamento físico e os poucos estudos com intervenção possuíam influência de outras variáveis, as quais estiveram associadas com tais mudanças. Assim, dificulta isolar e compreender o efeito do treinamento físico sobre a MI humana. Portanto, a partir de um delineamento controlado, o objetivo desse estudo foi investigar o efeito do treinamento físico aeróbio realizado em intensidade moderada sobre a composição da microbiota intestinal em humanos. Para isso, foram recrutados homens sedentários, entre 18 a 40 anos, universitários, com padrões alimentares semelhantes, não obesos e com ausência de quaisquer doenças, os quais foram randomizados em grupo controle (GC) e grupo treino (GT). Todos passaram pelas seguintes coletas: aplicação de questionários, coleta de sangue e fezes, avaliação da composição corporal e teste de esforço progressivo máximo, no pré- e pós-intervenção. Os voluntários do GT foram treinados em bicicletas ergométricas por 10 semanas (3x/semana; 50 minutos/dia; 60-65% VO2pico). A análise dos dados referentes à microbiota intestinal foram processados pelo software QIIME 2.0, as análises estatísticas foram realizadas pelo QIIME 2.0 e visualizadas no site do QIIME (https://view.qiime2.org/). Outras análises estatísticas foram realizadas no programa SPSS versão 25 por meio de análise de variância com medidas repetidas, utilizando \"grupo\" e \"tempo\" como fatores ou pelo teste Kruskal-Wallis. O nível de significância foi p<0,05. Após 10 semanas de intervenção houve aumento significante da capacidade aeróbia nos voluntários treinados, a qual promoveu aumento significante da família Lachnospiraceae e das espécies Roseburia sp. e Bacteroides ovatus. Em contrapartida houve redução do gênero Faecalibacterium e das espécies Lachnospira sp e Bilophila sp. Não foram detectadas diferenças nos índices de \'alfa\' e \'beta\' diversidade. Após o treinamento físico, o GT apresentou maior abundância de bactérias comensais em comparação ao GC, tais como, Faecalibacterium, Roseburia, Lachnospira e Akkermansia, enquanto que o GC apresentou aumento de bactérias ligadas à obesidade. A \'alfa\' diversidade, bem como, a abundância relativa da família Lachnospiraceae e do gênero Akkermansia se mostraram positivamente associados ao VO2pico. Deste modo, conclui-se que 10 semanas de treinamento físico foi eficiente em modificar a composição da MI em homens sedentários e minizar possíveis interferências negativas do comportamento sedentário / Gut microbiota (GM) is composed by million of microrganisms present in the gastrointestinal tract, especially in the distal gut. Recently, studies have suggested that aerobic training can modify the GM composition, for instance by increasing the commensal bacteria abundance, which positively influence the host organism. Nevertheless, some gaps exist: studies were conducted mostly in animal models in association with other design of diets and diseases; in humans, cross-sectional studies did not point to causality of training, and the few intervention studies were influenced by other variables, which have been associated with such changes. So, it is difficult to isolate and understand the aerobic training effect on the human GM. Therefore, from a controlled design, the objective of this study was to investigate the effect of aerobic training at moderate intensity on the human GM composition. For this, healthy and sedentary men, between 18 to 40 years old, university students, with similar diet habits and non-obese were recruited, and then were randomized in control group (CG) and training group (TG). The volunteers went through the following sample collections: questionnaires, blood and faeces samples, body composition and maximum progressive test, at pre and post intervention. TG volunteers were trained on stationary bicycles for 10 weeks (3x/week, 50 minutes/day, 60-65% VO2peak). The microbial data were conducted in QIIME 2.0 and statistical analyses were performed in QIIME 2.0 and visualized by QIIME view. Whereas other data was conducted in SPSS software version 25 by repeated measures of variance analysis with \"group\" and \"time\" as factors or Kruskal-Wallis test. The level of significance was p<0.05. After 10 weeks of intervention, there was a significant increasing in aerobic capacity in TG, which promoted a significant increasing in the relative abundance of Lachnospiraceae family and Roseburia sp. and Bacteroides ovatus species. In contrast, there was a reduction of the Faecalibacterium genus and Lachnospira sp. and Bilophila sp. species. No differences were detected in \'alfa\' and \'beta\' diversity. At post-intervention, TG showed a greater abundance of commensal bacteria, such as Faecalibacterium, Roseburia, Lachnospira and Akkermansia in comparison with CG, while CG presented an increase of bacteria related to obesity. The \'alfa\' diversity as well as the relative abundance of the Lachnospiraceae family and Akkermansia genus were positively associated with VO2peak. Thus, it was concluded that 10 weeks of aerobic training was efficient in modifying the GM composition in sedentary men and in minimizing possible negative interferences of the sedentary behavior

O desenvolvimento de biotecnologia de embriões em animais de produção é prejudicado por perdas no primeiro trimestre da gestação, idade em que o intestino primitivo está sendo estabelecido. O estudo das proteínas contidas no intestino primitivo nesta fase inicial da gestação pode aumentar o conhecimento sobre as vias moleculares envolvidas no desenvolvimento embrionário normal e em perdas de embriões, assim como a sua participação na organogênese e diferenciação celular. Intestino primitivo de embriões de bovinos a partir dos 39 SD ± 4 dias de desenvolvimento (variando de 33 a 45 dias) foram coletados em um matadouro local. As amostras foram processadas e agrupadas para análise proteômica shotgun label-free usando MudPIT (Multidimensional Protein Identification Technology). Análise funcional e de via foram feitas usando FatiGO (www.babelomics.org); Pathway Express (http://vortex.cs.wayne.edu/ ontoexpress) para identificar as ontologias relevantes e vias canônicas ou não-canônicas representada pelas proteínas expressas no Intestino primitivo. Um total de 74 proteínas ou sequências randômicas foram identificadas, correspondentes a 30 proteínas específicas expressas pelo Intestino primitivo bovino. Das 30 proteínas únicas, 21 proteínas foram utilizadas na ontologia e análise de vias. As análises mostraram um enriquecimento de ontologias relacionadas com a ligação (N = 5); atividade catalítica (N = 6); organela intracelular (N = 6). Houve um enriquecimento de ontologias associado às modificações do citoesqueleto; processo de diferenciação celular (N = 3), a migração celular (N = 4) e no metabolismo celular (N = 6). Além disso, a via e a análise de rede mostraram um enriquecimento de vias de comunicação entre células, tais como junções comunicantes e tight e as vias de adesão focal. Além disso, as vias envolvidas no movimento celular (por exemplo, vias de regulação do citoesqueleto de actina e a migração transendotelial de leucócitos) foram extremamente enriquecimento no grupo de proteínas expressas pelo Intestino primitivo bovino. Nossos resultados sugerem que as células do intestino primitivo tem alto perfil migratório e são compostas de células não totalmente diferenciadas, com alto metabolismo celular. A migração e a diferenciação destas células poderiam determinar o destino do embrião em desenvolvimento. Além disso, a compreensão da função e interação de proteínas expressas pelo embrião normal fornecerá informações sobre o impacto das biotecnologias reprodutivas no desenvolvimento do embrião durante a implantação e placentação. / The development of embryo biotechnology in farm animals is hampered by embryo losses in first trimester of gestation, period in which the primitive gut is being established. The study of proteins contained in the primitive gut at this early stage of pregnancy may increase the knowledge about the molecular pathways involved in normal embryonic development and loss of embryos, as well as their involvement in organogenesis and cell differentiation.primitive gut from bovine embryos on day 39 SD± 4 of development (ranging from 33 to 45 days) were collected at a local slaugtherhouse. The samples were processed and pooled for label-free shotgun proteomics analysis using MudPIT (Multidimensional Protein Identification Technology) tandem MSE acquisition. Functional and pathway analysis using FatiGo (www.babelomics.org); Pathway Express (http://vortex.cs.wayne.edu/ ontoexpress) and Ingenuity Pathway Analysis (www.ingenuity.com) were used to identify relevant ontologies and canonical or noncanonical pathways represented by the expressed proteins in the primitive gut. A total of 74 protein sequences were identified corresponding to 30 unique proteins expressed by the bovine primitive gut. out of 30 unique proteins, 21 proteins were used on the ontology and pathway analysis. The ontology analysis showed an enrichment of ontologies related to binding (N=5); catalytic activity (N=6); intracellular organelle (N=6). There was an enrichment of ontologies associated to cytoskeleton modifications; cell differentiation process (N=3); cellular migration (N=4) and cell metabolism (N=6). Furthermore, the pathway and the network analysis showed an enrichment of cell-to-cell communication pathways such as gap and tight junction, and focal adhesion pathways. In addition, pathways involved in cellular movement (regulation of actin cytoskeleton and leukocyte transendothelial migration) were extremely enrichment in the group of proteins expressed by the bovine primitive gut. Our results suggested that the cells from primitive gut have high migratory profile and are composed of not fully differentiated cells with high cellular metabolism. The proper migration and differentiation of these cells would dictate the fate of the developing embryo. Moreover, understanding the function and interaction of proteins expressed by normal embryo will give clues of the impact of the reproductive biotechnologies in embryo development during the window between implantation and placentation.

A caquexia é uma síndrome multifatorial marcada pela perda de peso, anorexia e desnutrição. Não há tratamento efetivo, pois a sua etiologia é obscura. A inflamação sistêmica é o papel chave da síndrome. Estudos apontam exercício e microbiota como moduladores da inflamação. Apesar da importância da microbiota e sua ligação com a inflamação e exercício, não há estudos em humanos que abordem esta correlação na caquexia. Este estudo investigou o impacto do treinamento físico (TF) aeróbio e crônico sobre a inflamação, microbiota intestinal e nutrição de pacientes com câncer caquéticos. Pacientes submetidos à cirurgia de câncer intestinal assinaram TCLE. Avaliamos peso, composição corporal, consumo alimentar; coletamos sangue, fezes e fragmento do cólon. Verificamos nos caquéticos: menor consumo proteico, ausência de correlação entre perda de peso e consumo proteico, e presença com IL-6; o TF aumentou massa corporal magra e total; reduziu celularidade, eosinófilos, plasmócitos e fibroblastos no intestino; e melhorou a relação Firmicutes e Bacteroidetes na microbiota fecal. Concluímos que há uma complexa interação entre fatores humorais, metabólicos e imunitários na caquexia, que pode ser favoravelmente modulada pelo treinamento físico aeróbio. / Cachexia is a multifactorial syndrome marked by weight loss, anorexia and malnutrition. There is no effective treatment because its etiology is obscure. Systemic inflammation is the key role of the syndrome. Studies show the exercise and microbiota as modulators of inflammation. Despite the importance of the microbiota and its connection with inflammation and exercise, there are no studies in humans that show this correlation in cachexia. This study investigated the impact of aerobic and chronic training (TF) on inflammation, gut microbiota and nutrition of cachectic cancer (CC) patients. Patients undergoing intestinal cancer surgery signed term of concent. We evaluated weight, body composition, food consumption; we collected blood, feces, and fragment of the colon. We observed in CC: lower protein consumption, none correlation between weight loss and protein consumption, and presence with IL-6; TF increased lean and total body mass; Reduced cellularity, eosinophils, plasma cells and fibroblasts in the gut; And improved the Firmicutes and Bacteroidetes ratio in the fecal microbiota. We conclude that there is a complex interaction between humoral, metabolic and immune factors in cachexia, which can be modulated by aerobic physical training.

Analisamos a ação da liraglutida na flora intestinal e perda de peso de dois modelos de obesidade: por dieta hiperlipidica (HFD) e obesidade genética (ob/ob). Os modelos foram tratados com o fármaco durante duas semanas. Perfis metabólicos foram feitos por meio de testes glicêmicos e insulínicos, histologia do fígado, região cecal e coxins gordurosos, ingestão alimentar, peso corporal e metagenômica do conteúdo cecal. O tratamento induziu perda de peso com melhora dos níveis glicêmicos e redução da inflamação na região cecal e do fígado e foi capaz de reduzir o acúmulo de gordura hepática promovendo a redução da EHNA. A metagenômica mostrou mudança taxonômica geral, bem como a abundância relativa de bactérias envolvidas com peso e controle glicêmico:redução de Proteobacterias e aumento de Akkermansia muciniphila. Apresentamos evidências do fármaco revertendo DGHNA/EHNA e a perda de peso associados às mudanças da microbiota. Sugerimos uma lista de alvos bacterianos que podem interferir no metabolismo energético para o controle clinico de doenças metabólicas. / The study analyzed the effects of liraglutide on gut microbiota and weight-loss in two obesity model: induced by high fat diet (HFD) and genetic obese mice (ob/ob). Models were treated with liraglutide for two weeks. Metabolic profiles were measured by glycemic and insulin test, histological liver, cecal region and fat pad morphologies, food intake, body weight and metagenomic of cecal contents. The treatment induced weight-loss, improvement of glycemic parameters and reduction of inflammatory cells in the cecum and the liver and reduced fat accumulation in liver reverting NASH. The metagenomic showed a general changed in taxonomic structure as well the relative abundance of weight-relevant:reduction of Proteobacteria and increases of Akkermansia muciniphila. We showed evidences that liraglutide leads to improvement of NASH and weight loss associated with changes in microbiota. Moreover, by the profile of the gut microbiota, we present a bacterial target list that may affect energetic metabolism inducing a metabolic clinical controlled profile.

A caquexia é uma síndrome multifatorial e multiorgânica associada ao câncer e outras doenças crônicas e caracterizada por perda involuntária grave de massa corporal, metabolismo e função imune alteradas, anorexia, fadiga e diminuição da qualidade de vida. A caquexia afeta cerca de 50% dos pacientes com câncer de cólon e é diretamente responsável pela morte de pelo menos 20% de todos os pacientes com câncer. A inflamação sistêmica, resultante da produção de mediadores inflamatórios, é comumente observada na caquexia do câncer. É possível que a inflamação possa derivar em parte da falha da função de barreira intestinal, promovendo uma ativação imunológica persistente. Este estudo envolveu 45 pacientes, divididos em grupos: WSC (câncer de peso estável) e CC (câncer com caquexia) e investigou a inflamação do cólon e a composição da microbiota intestinal na caquexia. Para tanto, realizou-se uma análise histológica por microscopia de luz e quantificação de fatores inflamatórios por Luminex® xMAP em biópsias de cólon retossigmóide (20 cm distantes do sítio tumoral) obtidas de pacientes CC e WSC durante a cirurgia para a retirada de tumor. Adicionalmente, realizou-se o seqüenciamento genético para a análise da composição da microbiota presente nas fezes dos pacientes. O número de agregados linfóides, eosinófilos e fibroblastos foi maior na mucosa do cólon em CC do que em WSC. A expressão da interleucina 7 (IL-7), da interleucina 13 (IL-13) e do fator de crescimento transformador beta 3 (TGF- &#946 3) aumentou significativamente no CC, em comparação com o WSC. Houve uma redução de bactérias dos gêneros Anaerotipes, Dorea e Coprococcus nos pacientes do grupo CC. Por outro lado, houve um aumento de bactérias dos gêneros Gemella e Parvimonas nos pacientes CC, comparado aos pacientes WSC. Os resultados sugerem alterações na barreira intestinal dos pacientes caquéticos, com um aumento do recrutamento de células imunes na mucosa do cólon, resposta inflamatória e de reparo teciduais. Não está claro se as respostas locais podem ser dirigidas pela disbiose ou podem promover a disbiose. Compreender o papel do intestino e da microbiota intestinal na patogênese desta síndrome pode levar ao desenvolvimento de novos alvos terapêuticos, a fim de minimizar a inflamação intestinal e os sintomas da caquexia. / Cachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterised by severe involuntary loss of body weight, disrupted metabolism, altered immune function, anorexia, fatigue and diminished quality of life. Cachexia affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation, the result of the production of inflammatory mediators, is commonly observed in cancer cachexia. It is possible that inflammation may partly derive from the failure of gut barrier function, yielding persistent immune activation. This study involved 45 patients, divided into groups: WSC (Weight Stable Cancer) and CC (Cachectic Cancer) and investigated the inflammation of the colon and the composition of the intestinal microbiota in cachexia. For this purpose, we carried out a morphological analysis by light microscopy and quantification of inflammatory factors by Luminex® xMAP in rectosigmoid colon biopsies (20 cm distant from the tumour site) obtained from cachectic (CC) and weight stable (WSC) colon câncer patients, during surgery. In addition, the genetic sequencing was performed to analyze the composition of the microbiota in the faeces of the patients. The number of lymphocytic aggregates, eosinophils and fibroblasts was higher in the mucosa of the colon in CC than in WSC. In regard to inflammatory cytokines, interleukin 7 (IL-7), interleukin 13 (IL-13) and transforming growth factor beta 3 (TGF- &#946 3) protein expression was significantly increased in CC, compared with WSC. There was a reduction of bacteria of the genus Anaerotipes, Dorea and Coprococcus in CC. On the other hand, there was an increase of bacteria of the genus Gemella and Parvimonas in CC patients, compared to WSC patients. The results suggest alterations in the intestinal barrier in cachectic patients, with an increase in the recruitment of immune cells in the mucosa of the colon, orchestrating an inflammatory response and in tissue repair. It is not clear whether local responses can be driven by dysbiosis or if it could promote dysbiosis. Understanding the role of the intestine and intestinal microbiota in the pathogenesis of this syndrome may lead to the development of new therapeutic targets in order to minimize intestinal inflammation and the symptoms of cachexia.

Introdução: Bactérias intestinais influenciam a resposta imune e conhecendo-se as ações imunomoduladoras da vitamina D passou-se a investigar sua relação com a microbiota. O status adequado desta vitamina está associado a uma composição mais saudável da microbiota, enquanto sua deficiência pode acarretar disbiose intestinal, endotoxemia, inflamação e resistência à insulina. O conhecimento de interações do status de vitamina D com a microbiota pode melhorar a compreensão da gênese de doenças crônicas mediadas pela inflamação. Objetivo: Examinou-se a associação da ingestão e concentração de vitamina D com a composição da microbiota fecal, marcadores inflamatórios e perfil bioquímico de participantes do Nutritionists Health Study. Métodos: Nesta análise transversal, 150 adultos jovens foram estratificados em tercis de consumo e de concentração de 25(OH)D e comparados quanto ao perfil clínico e inflamatório. A associação de 25(OH)D com a microbiota (sequenciamento do 16S rRNA, região V4, Illumina® MiSeq) foi testada por regressão linear múltipla. Resultados: A ingestão de vitamina D se associou aos níveis séricos (p < 0,05). Não foram observadas diferenças significantes de variáveis clínicas e inflamatórias entre os tercis de ingestão, exceto tendência de aumento do LPS com a redução da 25(OH)D (p-trend < 0,05). Prevotella foi mais abundante (log2FC 1,67; p < 0,01), e Haemophilus and Veillonella menos abundantes (log2FC -2,92 e -1,46; p < 0,01, respectivamente) no subgrupo com maior ingestão de vitamina D (referência) comparado aos outros grupos (primeiro e segundo tercis). PCR (r = -0,170; p = 0,039), selectina-E (r = -0,220; p = 0,007) e abundância de Coprococcus (r = -0,215; p = 0,008) e de Bifdobacterium (r = -0,269; p = 0,001) foram inversamente correlacionados com 25(OH)D. Após ajustes por idade, sexo, estação do ano e IMC, a 25(OH)D manteve associação inversa com Coprococcus ( = -9,414; p = 0,045) e Bifdobacterium ( = -1,881; p = 0,051), mas a significância desapareceu com a adição de marcadores inflamatórios aos modelos. Conclusão: Associações de ingestão e concentração de vitamina D com abundância de certos gêneros da microbiota sugerem que sua ação imunomoduladora poderia influenciar a composição bacteriana. Abundância relativamente maior de gram-negativos (Haemophilus e Veillonella) pode ter sido facilitada pela baixa ingestão e/ou concentração da vitamina. Menor proporção de bactérias benéficas (Coprococcus e Bifidobacterium) poderia estimular a resposta imune e inflamação. Concluímos que a participação da vitamina D na manutenção da homeostase imune deve ocorrer em parte pelas interações com a microbiota intestinal, embora o delineamento transversal impeça assegurar relações tipo causa-efeito. / Introduction: Gut bacteria influence the immune response and due the immunomodulatory actions of vitamin D, it has been investigated its relationship with the microbiota. Adequate status of this vitamin is associated with adequate composition of the microbiota, while its deficiency can cause gut dysbiosis, endotoxemia, inflammation and insulin resistance. The knowledge of interactions of vitamin D status with the microbiota may improve the understanding of the genesis of inflammation-mediated chronic diseases. Objective: We examined the association of vitamin D intake and concentration with the composition of fecal microbiota, inflammatory markers and biochemical profile of participants from the Nutritionists\' Health Study. Methods: In this cross-sectional analysis, 150 healthy young adults were stratified into tertiles of intake and concentrations of vitamin D and their clinical and inflammatory profiles were compared. The association between 25(OH)D and fecal microbiota (16S rRNA sequencing, V4 region, Illumina® MiSeq) was tested by multiple linear regression.) Results: Vitamin D intake was associated with its concentration (p<0.05). There were no significant differences in clinical and inflammatory variables across tertiles of intake, except for a trend of LPS increases with reduction of 25(OH)D (p-trend <0.05). Prevotella was more abundant (log2FC 1.67; p <0.01), and Haemophilus and Veillonella less abundant (log2FC -2,92 e -1.46; p <0.01, respectively) in subset with the highest vitamin D intake (reference) than that observed in the other subset (first plus second tertiles). CRP (r=-0.170, p=0.039), E-selectin (r=-0.220, p=0.007) and abundances of Coprococcus (r=-0.215, p=0.008) and Bifdobacterium (r=-0.269, p=0.001) were inversely correlated with 25(OH)D. After adjusting for age, sex, season and BMI, the 25(OH)D maintained inversely associated with Coprococcus (=-9.414, p=0.045) and Bifdobacterium (=-1.881, p=0.051), but significance disappeared following the addition of inflammatory markers in the regression models. Conclusion: Association of vitamin D intake and concentration with abundance of certain genera of microbiota suggests that its immunomodulatory action could influence the bacterial composition. Relatively higher abundance of gram-negative (Haemophilus and Veillonella) may have been facilitated by the low intake and/or concentration of the vitamin. Lower proportion of beneficial bacteria (Coprococcus and Bifidobacterium) could stimulate the immune response and inflammation. We conclude that the role of vitamin D in maintaining immune homeostasis should occur in part by interactions with the gut microbiota, although the cross-sectional design does not allow ensuring cause-effect relationships.

O objetivo deste trabalho foi avaliar a adição de diferentes níveis de levedura (Saccharomyces cerevisiae) inativa e desidratada às rações, associados ao plasma sangüíneo e ao ácido glutâmico, sobre o desempenho e morfologia intestinal de leitões na fase inicial. Para tanto, foram realizados dois experimentos, cada um com três tratamentos de quatro repetição com 22 animais em fase de creche (21 à 59 dias), totalizando 264 leitões por experimento. Os animais foram distribuídos em delineamento em blocos casualizados nos dois experimentos. Ambos foram divididos em quatro fases experimentais correspondentes as trocas das dietas: pré - inicial 1(21-28), pré - inicial 2 (29-35), pré - inicial 3 (36-42). O experimento 1 teve os seguintes tratamentos: Ração Pré Inicial 1 - A - 5% de levedura inativa, 4% de plasma, 1% de ácido glutâmico; B - 3% de levedura inativa, 2% de levedura hidrolisada, 4% de plasma e 1% de ácido glutâmico; C - 3% de levedura inativa, 2% de levedura hidrolisada, 4% de plasma. Ração Pré Inicial 2 - A - 4% de levedura inativa, 3% de plasma, 0,8% de ácido glutâmico; B - 3% de levedura inativa, 1% de levedura hidrolisada, 3% de plasma e 0,8% de ácido glutâmico; C - 3% de levedura inativa, 1% de levedura hidrolisada, 3% de plasma. Ração Pré Inicial 3 - A - 2% de levedura inativa, 1,5% de plasma, 0,6% de ácido glutâmico; B - 2% de levedura, 0,5% de levedura hidrolisada, 1,5% de plasma e 0,6% de ácido glutâmico; C - 2% de levedura, 0,5% de levedura hidrolisada, 1,5% de plasma. E o experimento 2 teve os seguintes tratamentos: Ração Pré Inicial 1 - A - 5% de levedura inativa, 3% de plasma; B - 5% de levedura inativa, 3% de plasma e 1% de ácido glutâmico; C - 3% de levedura inativa, 2% de levedura hidrolisada, 3% de plasma e 1% de ácido glutâmico. Ração Pré Inicial 2 - A - 4% de levedura inativa, 2% de plasma; B - 4% de levedura inativa, 2% de plasma, 0,8% de ácido glutâmico; C - 3% de levedura inativa, 1% de levedura hidrolisada, 2% de plasma e 0,8% de ácido glutâmico. Ração Pré Inicial 3 - A - 2% de levedura inativa, 1,0% de plasma; B - 2% de levedura inativa, 1,0% de plasma, 0,6% de ácido glutâmico; C - 2% de levedura, 0,5% de levedura hidrolisada, 1,0% de plasma e 0,6% de ácido glutâmico. A levedura hidrolisada demonstrou aspectos positivos para sua utilização em dieta de leiões nas fases críticas pós desmama podendo promover melhora no desempenho zootécnico e na morfologia intestinal dos animais. / The objective of this study was to evaluate the addition of different levels of hidrolysed and inactive yeast (Saccharomyces cerevisiae) in feed, with spray dried blood plasma and glutamic acid on performance and intestinal morphology of weaned piglets. Two experiments were conducted, each with three treatmens, four replicates with 22 animals in the nursery phase (21 to 59 days of age), totaling 264 pigs per experiment. The piglets were distributed in randomized block design in both experiments. The experiments were divided in four phases corresponding experimental diets: pre - starter 1 (21-28), pre - starter 2 (29-35), pre - starter 3 (36-42). Experiment 1 had the following treatments: Pre starter 1 - A - 5% of inactive yeast, 4% plasma, 1% glutamic acid; B - 3% of inactive yeast, 2% hydrolyzed yeast, 4% plasma and 1% glutamic acid; C - 3% inactive yeast, 2% hydrolyzed yeast, 4% of plasma. Pre starter 2 - A - 4% inactive yeast, 3% plasma, 0.8% glutamic acid; B - 3 % inactive yeast, 1% hydrolyzate yeast, 3% plasma, 0.8% glutamic acid; C - 3% inactive yeast, 1% hydrolyzate yeast, 3% of plasma. Pre starter 3 - 2% inactive yeast, 1.5% plasma, 0.6% glutamic acid; B - 2% inactive yeast, 0.5% hydrolyzate yeast, 1.5% and plasma 0 6% glutamic acid; C - 2% inactive yeast, 0.5% hydrolyzate yeast, 1.5% plasma. And the experiment 2 had the following treatments: Pre starter 1 - A - 5% inactive yeast, 3% plasma; B - 5% inactive yeast, 3% plasma and 1% glutamic acid; C - 3% inactive yeast , 2% hydrolyzate yeast, 3% plasma and 1% glutamic acid. Pre starter 2 - A - 4% inactive yeast, 2% plasma; B - 4% inactive yeast, 2% plasma, 0.8% glutamic acid; C - 3% inactive yeast, 1% hydrolyzate yeast, 2 % plasma and 0.8% of glutamic acid. Pre starter 3 - A - 2% inactive yeast, 1.0% plasma; B - 2% inactive yeast, 1.0% plasma, 0.6% glutamic acid; C - 2% inactive yeast, 0, 5% hydrolyzate yeast 1.0% of plasma and 0.6% glutamic acid. Yeast hydrolyzate showed positive aspects to their use in diet after weaning can promote improvement in performance and intestinal morphology of animals.

Research into the gut microbiome has revealed the widespread influence that microbial species have on their host. Host genetics and environmental factors influence the abundance and diversity of the bacterial species living within the gastrointestinal tract. When the normal composition of the gut microbiota is altered, a dysbiotic state incurs. Inflammatory bowel disease (IBD) is a chronic/relapsing inflammatory disorder of the intestinal mucosa, which is characterized by a state of dysbiosis. Despite the large amount of information studying the role dysbiosis has in the pathogenesis of IBD, it is not clear how the altered microbial composition of the gut in IBD patients leads to susceptibility to enteric pathogens such as Clostridium difficile. This study aims to highlight the features of the gastrointestinal tract that are modified as a result of dysbiosis in the IBD population, and how these features facilitate colonization by C. difficile and symptom development. Review of the available literature demonstrated that the depletion of Clostridial cluster XIVa in IBD-associated dysbiosis alters bile acid metabolism and butyrate fermentation in the colon, ultimately promoting germination of C. difficile spores and weakening the gut's immune response against toxin-mediated inflammation. From continued research into the gut microbiota, more will be understood of how these microbial organisms influence human health and disease.