Intestinal homeostasis and host defense as promoted by commensal bacteria and the colonic mucus layer

The intestinal tract harbours the largest population of microbes in the human body where they play an important role in promoting the health of their host. If the composition of these microbes is altered, this may lead to dysbiosis that triggers or exacerbates intestinal and extra-intestinal diseases. Probiotics have been investigated as a complementary therapy in dysbiosis-related diseases. However, their effectiveness in treating severe conditions such as Inflammatory Bowel Disease (IBD) is quite variable and have shown controversial results. To address the importance of a personalized probiotic approach to treat intestinal inflammation, we first examined the effect of personalized bacteria using a model of chemical induced colitis. The animals that received commensals isolated from their own feces were more protected against inflammation as they showed reduced signs of colitis, less histological damage and lower levels of inflammatory markers as compared to mice given a commercial probiotic strain. Next, the role of the intestinal mucin Muc2 and the Core-1 enzyme that glycosylates it were explored using the Citrobacter rodentium model of infectious colitis. The intestinal mucus layer is the first line of defense in the intestine and is largely composed of the secreted mucin Muc2. Since almost all enteric bacteria must cross the overlying mucus layer to infect the host, the mucus-enteric bacterial interactions provide fundamental knowledge about infectious diseases as well as inflammatory conditions linked to dysbiosis (e.g. IBD). Specifically, we compared C. rodentium susceptibility by infecting WT, Muc2 -/-, core 3 (C3GnT) -/-, core -1 (C1galt1) -/-, and C1galt1 f/f mice. While C3GnT -/- mice showed a very similar phenotype to WT mice with only mild inflammation, complete absence of Muc2 or just core 1 derived O-glycans resulted in significantly higher histological damage, barrier disruption, and increased pathogen burdens. Interestingly, the supplementation of tributyrin protected mice against infection resulting in less histological damage and lower C. rodentium colonization as compared to control groups. These studies highlight a novel personalized therapy that may be considered relevant to diseases affected by dysbiosis as well as the key role of Muc2 and its core 1 glycosylation in host defense against enteric infections.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat

Efeito de uma bebida probiótica (Enterococcus faecium CRL 183 e Bifidobacterium longum ATCC 15707) à base de extrato aquoso de soja no desenvolvimento de colite quimicamente induzida em ratos

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), comprise a group of disorders and their main characteristic is an inflammation of the intestinal mucosa. Although its origin is not yet fully known, there is growing evidence linking genetics predisposition, composition of the intestinal microbiota and immune system factors as precursors for the initiation and progression of these pathologies. The use of certain probiotic microorganisms has been considered as promising way to reduce the risk of inflammatory bowel disease, specifically ulcerative colitis. Several mechanisms have been proposed to explain the benefits of probiotics, indicating that some bacterial strains are able to positively modulate the intestinal microbiota and the immune system, and produce metabolites with anti-inflammatory capacity. As the effects and the mechanisms involved are strain-specific, further studies are extremely important to understand the interactions between gut microbiota and host, contributing to the knowledge on therapeutic potential of probiotics in diseases related to dysbiosis. This current paper aims to bring together the various results and information based on scientific evidence that are related to probiotics and the inflammatory bowel disease, with emphasis on the possible mechanisms involved in this action. Furthermore, the effects of daily ingestion of a product based on an aqueous extract of soybean, fermented by Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 with the addition of Bifidobacterium longum ATCC 15707, were also investigated on chemically induced colitis in rats. Colitis was induced by 4% dextran sulfate sodium (DSS), dissolved in the drinking water supplied to the animal, which was ingested daily for a period of seven days. The animals will then be assigned randomly to four groups (n=10): Group C: healthy animals that do not receive the products under study; Group CL: ...As doenças inflamatórias intestinais (DII), entre elas a doença de Crohn (DC) e a retocolite ulcerativa idiopática (RCUI) compreendem um grupo de patologias que possuem como principal característica a inflamação da mucosa intestinal. Embora sua origem ainda não seja completamente conhecida, existe uma crescente evidência baseada em estudos recentes associando predisposição genética, composição da microbiota intestinal e sistema imunológico como fatores precursores para a iniciação e progressão dessas patologias. O uso de determinadas cepas probióticas vem sendo apontado como uma forma promissora de se reduzir o risco de doenças inflamatórias intestinais, mais precisamente da colite ulcerativa. Diversos mecanismos têm sido propostos para explicar os benefícios dos probióticos, indicando que algumas cepas bacterianas são capazes de modular positivamente a microbiota intestinal e o sistema imune, além de produzirem metabólitos com capacidade antiinflamatória. Como os efeitos e os mecanismos de ação envolvidos são cepa-específicos, é de extrema importância a realização de novos estudos para compreender as interações entre microbiota intestinal e hospedeiro, contribuindo para o entendimento do potencial terapêutico dos probióticos nas doenças relacionadas ao desequilíbrio da microbiota intestinal. O presente trabalho se propõe a investigar o efeito da ingestão diária de um produto à base de extrato aquoso de soja, fermentado com Enterococcus faecium CRL 183 e Lactobacillus helveticus 416 e com adição de Bifidobacterium longum ATCC 15707, na colite induzida quimicamente em ratos. A colite foi induzida, pela administração de dextran sulfato de sódio (DSS) a 4%, que foi dissolvido na água fornecida diariamente aos animais e administrado durante um período de sete dias. Os animais foram distribuídos aleatoriamente em cinco grupos (n=10): Grupo C: Animais sadios que não receberam os produtos em estudo. ...Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Probiotics: the scientific evidence in the context of inflammatory bowel disease

Inflammatory bowel disease (IBD) generally comprises Crohn's disease (CD) and ulcerative colitis (UC), and their main characteristic is the intestinal mucosa inflammation. Although its origin is not yet fully known, there is growing evidence related to genetics, intestinal microbiota composition, and the immune system factors such as precursors for the initiation and progression of intestinal conditions. The use of certain probiotic microorganisms has been touted as a possible and promising therapeutic approach in reducing the risk of inflammatory bowel disease, specifically ulcerative colitis. Several mechanisms have been proposed to explain the benefits of probiotics, indicating that some bacterial strains are able to positively modulate the intestinal microbiota and the immune system, and to produce metabolites with anti-inflammatory capacity. The aim of this paper is to bring together the various results and information, based on scientific evidence, that are related to probiotics and inflammatory bowel disease, emphasizing the possible mechanisms involved in this action.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Consumo de leite informal na cidade de Araraquara-SP

Brazil is one of the largest milk producers in the world, with an estimated total production of 37 billion liters in 2014, Of this total, 33% is not inspected, being destined for the informal market, Objective: The aim of this study was to collect and analyze data on raw milk consumption in the city of Araraquara (SP, Brazil). Methods: Regular milk consumers were provided with exploratory questionnaires in locations chosen for convenience, The reproducibility of each question was tested by Kappa statistics, Associations of interest were 2 detected by the chi-squared (χ ) or Fisher's exact test. Statistical significance was established when p0.05. Results: Most of the volunteers (97.6%) reported consuming milk daily, the type of milk chosen most, mainly for ease of purchase, being boxed UHT, Regarding raw milk, 15.3% of volunteers said they consume it, the greatest consumption being observed among subjects with complete secondary or higher education, The majority of the participants reported knowing of the possibility of diseases being transmitted by unprocessed milk, Most respondents pointed to "flavor" as the main reason for consumption. Only 15.3% reported that someone in their house had become ill from drinking milk, and only 4.1% attributed this to the ingestion of raw milk, Conclusion: It was found that 15.3% of consumers drink raw milk in the city of Araraquara, which is more than the expected proportion in a medium sized city located in the state of São Paulo

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

This work investigates the effect of a soy-based probiotic drink (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) on the fecal microbiota composition, body weight and inflammatory parameters in diet-induced obese mice. The probiotic group had a lower body weight until 9th week of the study, reduced area and diameter of adipocytes, and showed a significant increase of IL-6 and IL-10 compared to the obesite non-treated group. The intake of a high-fat diet results in an increase of Lactobacillus spp. while the probiotic drink positively modulates the intestinal microbiota by maintaining the population of microorganisms belonging to the phylum Bacteroidetes and increases Bifidobacterium spp. Our study finds that the regular intake of this probiotic drink is able to reduce body weight gain and the size of adipocytes while modulating the fecal microbiota and the immune profile of animals, therefore acting in a beneficial manner in the control of obesity.Fil: de Carvalho Marchesin, Juliana. Universidade Estadual de Campinas; BrasilFil: Sbaglia Celiberto, Larissa. Universidade Estadual de Campinas; BrasilFil: Botinhon Orlando, Allan. Universidade Estadual de Campinas; BrasilFil: Ivo de Medeiros, Alexandra. Universidade Estadual de Campinas; BrasilFil: Pinto, Roseli Aparecida. Universidade Estadual de Campinas; BrasilFil: Sampaio Zuanon, José Antônio. Universidade Estadual de Campinas; BrasilFil: Spolidorio, Luis Carlos. Universidade Estadual de Campinas; BrasilFil: dos Santos, Andrey. Universidade Estadual de Campinas; BrasilFil: Taranto, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Umbelino Cavallini, Daniela Cardoso. Universidade Estadual de Campinas; Brasi

Controle de qualidade e avaliação dos efeitos do consumo do leite de soja produzido na UniverSoja

The UNISOJA project attends daily, by providing soy milk, institutions assisted by the Municipal Government of Araraquara, children from lowincome families and with lactose intolerance and/ or milk protein allergy. Control quality of soy milk is necessary to ensure the safety of the beneficiaries. On the other hand, the evaluation of children assisted is important to measure the impact of the project on the population. In this sense, the present study aimed to verify the physical-chemical and microbiological properties of soy milk produced at School of Pharmaceutical Sciences of Araraquara (UniverSoja). In addition, were verified the effects of product consumption in children assisted by the project. The results indicate that soy milk produced by UniverSoja has good microbiological quality and is safe for human consumption. The evaluation of the beneficiaries highlighted the importance of UNISOJA project for community, noting an improvement in quality of life of children participating of the program.O projeto UNISOJA atende, diariamente, através do fornecimento de “leite” de soja, instituições assistidas pela Prefeitura Municipal, crianças pertencentes a famílias de baixa renda e portadoras de intolerância à lactose e/ou alergia à proteína do leite. O Controle de qualidade do “leite” de soja distribuído é importante para garantir a segurança dos beneficiários. Por outro lado, a avaliação das crianças atendidas se faz necessária como uma forma de dimensionar o impacto do projeto junto à população. Nesse sentido, o presente trabalho teve por objetivo o controle físico-químico e microbiológico do “leite” de soja produzido na planta piloto instalada nas dependências da Faculdade de Ciências Farmacêuticas de Araraquara (UniverSoja). Em adição, foram verificados os efeitos do consumo do produto em crianças beneficiadas pelo projeto. Os resultados indicam que o produto produzido na UniverSoja apresenta boa qualidade microbiológica e é seguro para o consumo humano. A avaliação dos beneficiários evidenciou a importância do projeto UNISOJA frente à comunidade, constatando-se melhora na qualidade de vida das crianças atendidas pelo programa

Probiotic soy product supplemented with isoflavones Improves the lipid profile of moderately hypercholesterolemic men: a randomized controlled trial

Cardiovascular disease is the leading cause of worldwide morbidity andmortality. Several studies have demonstrated that specific probiotics affect the host?s metabolism and may influence the cardiovascular disease risk. Objectives: The aim of this study was to investigate theinfluence of an isoflavone-supplemented soy product fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 on cardiovascular risk markers in moderately hypercholesterolemic subjects. Design: Randomized placebo-controlled double-blind trial Setting: São Paulo State University in Araraquara, SP, Brazil. Participants: 49 male healthy men with total cholesterol (TC) >5.17 mmol/L and <6.21 mmol/L Intervention: The volunteers have consumed 200 mL of the probiotic soy product (group SP-1010 CFU/day), isoflavone-supplemented probiotic soy product (group ISP?probiotic plus 50 mg of total isoflavones/100 g) or unfermented soy product (group USP-placebo) for 42 days in a randomized, double-blind study. Main outcome measures: Lipidprofile and additional cardiovascular biomarkers were analyzed on days 0, 30 and 42. Urine samples (24 h) were collected at baseline and at the end of the experiment so as to determine the isoflavones profile. Results: After 42 days, the ISP consumption led to improved total cholesterol, non-HDL-C (LDL + IDL + VLDL cholesterol fractions) and electronegative LDL concentrations (reduction of 13.8%, 14.7% and 24.2%, respectively, p < 0.05). The ISP and SP have prevented the reduction of HDL-C level after 42 days. The C-reactive protein and fibrinogen levels were not improved.The equol production by the ISP group subjects was inversely correlated with electronegative LDL concentration. Conclusions: The results suggest that a regular consumption of this probiotic soy product, supplemented with isoflavones, could contribute to reducing the risk of cardiovasculardiseases in moderately hypercholesterolemic men, through the an improvement in lipid profile and antioxidant properties.Fil: Cavallini, Daniela Cardoso Umbelino. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Manzoni, Marla Simone Jovenasso. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Bedani, Raquel. Universidade de Sao Paulo; BrasilFil: Roselino, Mariana Nougalli. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Celiberto, Larissa Sbaglia. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Vendramini, Regina Célia. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Font, Graciela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Abdalla, Dulcinéia Saes Parra. Universidade de Sao Paulo; BrasilFil: Pinto, Roseli Aparecida. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Rosetto, Daniella. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Valentini, Sandro Roberto. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Rossi, Elizeu Antonio. Universidade Estadual Paulista Julio de Mesquita Filho; Brasi

Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis.

BACKGROUND:Some probiotic strains have the potential to assist in relieving the symptoms of inflammatory bowel disease. The impact of daily ingestion of a soy-based product fermented by Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 with the addition of Bifidobacterium longum ATCC 15707 on chemically induced colitis has been investigated thereof within a period of 30 days. METHODS:Colitis was induced by dextran sulfate sodium. The animals were randomly assigned into five groups: Group C: negative control; Group CL: positive control; Group CLF: DSS with the fermented product; Group CLP: DSS with the non-fermented product (placebo); Group CLS: DSS with sulfasalazine. The following parameters were monitored: disease activity index, fecal microbial analyses, gastrointestinal survival of probiotic microorganisms and short-chain fatty acids concentration in the feces. At the end of the protocol the animals' colons were removed so as to conduct a macroscopical and histopathological analysis, cytokines and nitrite quantification. RESULTS:Animals belonging to the CLF group showed fewer symptoms of colitis during the induction period and a lower degree of inflammation and ulceration in their colon compared to the CL, CLS and CLP groups (p<0.05). The colon of the animals in groups CL and CLS presented severe crypt damage, which was absent in CLF and CLP groups. A significant increase in the population of Lactobacillus spp. and Bifidobacterium spp. at the end of the protocol was verified only in the CLF animals (p<0.05). This group also showed an increase in short-chain fatty acids (propionate and acetate). Furthermore, the intestinal survival of E. faecium CRL 183 and B. longum ATCC 15707 in the CLF group has been confirmed by biochemical and molecular analyzes. CONCLUSIONS:The obtained results suggest that a regular intake of the probiotic product, and placebo to a lesser extent, can reduce the severity of DSS-induced colitis on rats

Fecal SCFA concentration (mM/g) from different groups throughout the experimental period.

<p>Same lowercase letters indicate that there was no difference when comparing times. Same capital letters indicate that there was no difference when comparing groups (Tukey test, p<0.05). <b>Group C:</b> healthy animals that did not receive the products under study. <b>Group C:</b> negative control–healthy animals; <b>Group CL:</b> positive control—DSS; <b>Group CLF:</b> DSS with the fermented product; <b>Group CLP:</b> DSS with the non-fermented product (placebo); <b>Group CLS:</b> DSS with sulfasalazine. <b>T0</b> = before products administration, <b>T1</b> = one week after products administration, <b>T2</b> = colitis induction period, <b>T3</b> = one week after the end of the induction <b>T4</b> = at the end of the experiment. <b>A</b> = acetate, <b>B</b> = propionate, <b>C</b> = butyrate.</p

Representative photomicrographs from the different experimental colon groups, stained with hematoxylin/eosin.

<p><b>Group C:</b> healthy animals that did not receive the products under study. <b>Group C:</b> negative control–healthy animals; <b>Group CL:</b> positive control—DSS; <b>Group CLF:</b> DSS with the fermented product; <b>Group CLP:</b> DSS with the non-fermented product (placebo); <b>Group CLS:</b> DSS with sulfasalazine. (100x and 400x). <b>1:</b> healthy epithelium; <b>2 and 5</b>: epithelium with severe crypt damage, featuring as ulceration area; <b>3 e 4:</b> inflammatory cell infiltrated areas, however with no crypt alteration. n = 10.</p