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Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background: Synbiotics, probiotics and prebiotics are being added to infant formula. This study was an in-depth evaluation of research on infants fed infant formula containing synbiotics, probiotics or prebiotics and was carried out in two phases. Phase one included two systematic reviews that assessed if synbiotics, probiotics or prebiotics led to improved growth and clinical outcomes in formula fed full term and preterm infants. Phase two included two studies: A systematic review compared the methodological quality and outcomes of industry and non-industry sponsored randomized controlled trials (RCTs) and a descriptive study evaluated how the food industry applies the knowledge and evidence gained from probiotics, prebiotics or synbiotics research in infants. The research questions were: Does the consumption of probiotics, prebiotics or synbiotics supplemented infant formula lead to improved clinical outcomes in infants? Is there an association between source of funding and methodological quality, clinical outcomes and author’s conclusions in trials using probiotics, prebiotics or synbiotics supplemented formula in infants? Does the food industry use the evidence gained through probiotics, prebiotics and synbiotics research trials on infants for the benefit of the general paediatric population? The hypotheses were: Consumption of probiotics, prebiotics or synbiotics by infants leads to improved clinical outcomes; The source of funding in research trials using probiotics, prebiotics or synbiotics supplemented formula in infants is associated with outcomes in favour of the sponsor’s products and authors’ conclusions; Methodological qualities of non-industry sponsored trials are equivalent to industry sponsored trials; Evidence gathered through probiotics, prebiotics and synbiotics research is implemented by the food industry. Methods: Phase one: Both systematic reviews on preterm and full term infants: Cochrane methodology was followed using RCTs which compared preterm or full term formula containing probiotics, prebiotics or synbiotics to conventional infant formula with / without placebo among healthy preterm or full term infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Phase two: In the systematic review, Cochrane methodology was used to assess the risk of bias of included RCTs. Association between source of funding and risk of bias, clinical outcomes and conclusions were assessed. In the descriptive study, all listed companies that manufacture infant food products with added synbiotics, probiotics or prebiotics for infants were identified and invited to participate. A letter of invitation was sent and if they expressed willingness to take part in the study, a questionnaire with a written consent form was sent. Descriptive statistics and associations between categorical variables were to be tested using a Chi-square test. Results: Phase one: Review on preterm infants: 8 studies were included. Probiotics increased stool frequency with no effect on other clinical outcomes. Prebiotics increased stool frequency and bifidobacteria counts only. Review on full term infants: 25 studies were included. Synbiotics improved stool frequency but had no effect on other clinical outcomes. Probiotics did not have an effect on any clinical outcome. Prebiotics increased weight gain and stool frequency with no effect on other outcomes. Phase two: Systematic review: 67 studies were included, majority were funded by food industry. There was no significant association between the source of funding and four domains (sequence generation, allocation concealment, blinding, selective reporting), majority of reported clinical outcomes or authors’ conclusions. Source of funding was significantly associated with two domains (incomplete outcome data, free of other bias), antibiotic use and conclusions on weight gain. Descriptive study: 25 companies were identified and invited to participate. No company agreed to participate in the survey for different reasons. Conclusions Phase one: Review on preterm infants: There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants. Review on full term infants: There is not enough evidence to state that supplementation of term infant formula with synbiotics, probiotics or prebiotics does result in improved growth or clinical outcomes in term infants. There is no data available to establish if synbiotics are superior to probiotics or prebiotics. Phase two: Systematic review: In RCTs on infants fed infant formula containing probiotics, prebiotics or synbiotics, the source of funding does not influence majority of outcomes in favour of the sponsors’ products. More non-industry funded research is needed to further assess the impact of funding on reported clinical outcomes and authors’ conclusions. Descriptive study: Due to companies refusing to participate in this study, no conclusion could be drawn on how the food industry applies evidence gained through probiotics, prebiotics or synbiotics research on infants. More transparency is needed from the infant formula manufactures on how they apply the evidence gained from probiotic, prebiotic or synbiotic research on infants. / AFRIKAANSE OPSOMMING: Agtergrond Synbiotika, probiotika en prebiotika word gereeld by baba formule gevoeg. Hierdie studie was 'n in-diepte evaluering van navorsing oor babas gevoed met formule melk wat synbiotika, probiotika of prebiotika bevat en is uitgevoer in twee fases. Fase een het twee sistematiese oorsigte ingesluit wat die rol van synbiotika, probiotika en prebiotika op verbeterde groei en kliniese uitkomste van formule gevoede volterm babas en vroeg gebore babas evalueer het. Fase twee het bestaan uit twee studies: 'n sistematiese oorsig wat die metodologiese kwaliteit en uitkomste van die bedryf en nie-bedryf geborgde ewekansige gekontroleerde proewe (RCTs) evalueer het, asook 'n beskrywende studie wat die kennis en toepassing van bewyse oor die effektiewiteit van probiotika, prebiotika of synbiotika in die voedsel industrie bestudeer het. Die hipotese stellings was: verbruik van probiotika, prebiotika of synbiotika by babas lei tot verbeterde kliniese uitkomste; die bron van befondsing vir synbiotics, probiotika of prebiotika navorsing beïnvloed uitkomste ten gunste van die borg se produkte; bewyse ingesamel deur middel van probiotika, prebiotika en synbiotika navorsing word geïmplementeer deur die voedselindustrie. Metodes Fase een: Beide sistematiese oorsigte op volterm en premature babas: Cochrane metodes is gevolg deur ewekansige, gekontroleerde studies wat vol termyn of premature formule met probiotika, prebiotika of synbiotika met konvensionele baba formule met / sonder plasebo onder gesonde volterm of premature babas bestudeer. Die gemiddelde verskil (MD) en die ooreenstemmende 95% vertrouensintervalle is gebruik vir deurlopende uitkomste, risiko verhouding (RR) en die ooreenstemmende 95% CI vir tweeledige uitkomste. Fase twee: In die sistematiese oorsig is Cochrane metodiek gebruik om die risiko van vooroordeel van ingesluite ewekansige, gekontroleerde studies te evalueer. Assosiasie tussen bron van befondsing en die risiko van vooroordeel, asook kliniese uitkomste en gevolgtrekkings was beoordeel. In die beskrywende studie, is alle genoteerde maatskappye wat babavoeding produkte vervaardig met bygevoegde synbiotika, probiotika of prebiotika vir babas geïdentifiseer en uitgenooi om deel te neem. 'n Uitnodigingsbrief is vir die relevante maatskappye gestuur om hul bereidwilligheid om deel te neem te bevestig. Indien hulle wel bereid was om deel te neem was 'n vraelys met 'n skriftelike toestemming vorm gestuur. Beskrywende statistiek en assosiasies tussen kategoriese veranderlikes was getoets met behulp van 'n Chi-kwadraat toets. Resultate Fase een: Oorsig oor premature babas: 8 studies was ingesluit. Probiotika verhoog stoelgang frekwensie met geen effek op ander kliniese uitkomste. Prebiotika verhoog ook stoelgang frekwensie en slegs bifidobakteriële tellings. Oorsig oor die vol termyn babas: 25 studies was ingesluit. Synbiotika verbeter stoelgang frekwensie, maar het geen effek op ander kliniese uitkomste gehad nie. Probiotika het nie 'n effek op enige kliniese uitkoms gehad nie. Prebiotika verhoog gewigstoename en stoelgang frekwensie met geen effek op ander uitkomste. Fase twee: Sistematiese oorsig: 67 studies was ingesluit, en die meerderheid was befonds deur die voedsel bedryf. Daar was geen beduidende assosiasie tussen die bron van befondsing en vier gebiede (toekenningsvolgorde, toekenningsverberging, studie verblinding, selektiewe verslaggewing), en die meerderheid van gerapporteerde kliniese uitkomste of skrywers se gevolgtrekkings. Die bron van befondsing was beduidend verbind met twee gebiede (onvolledige uitslag data, vry van ander vooroordeel), antibiotika gebruik en gevolgtrekkings op gewigstoename. Beskrywende studie: 25 maatskappye is geïdentifiseer en genooi om deel te neem. Geen maatskappy het ingestem om deel te neem aan die studie om verskillende redes. Gevolgtrekkings Fase een: Oorsig oor premature babas: Daar is nie genoeg bewyse dat die aanvulling met probiotika of prebiotika resultate in verbeterde groei en kliniese uitkomste in uitsluitlik formule gevoede premature babas tot gevolg het nie. Oorsig oor die volle termyn babas: Daar is nie genoeg bewyse om te sê dat die aanvulling van term baba formule met synbiotika, probiotika of prebiotika lei tot verbeterde groei of kliniese uitkomste in termyn babas. Daar is geen inligting beskikbaar om te stel of synbiotika beter is as probiotika of prebiotika nie. Fase twee: Sistematiese oorsig: In studies op babas gevoed met formule melk wat probiotika, prebiotika of synbiotika bevat het, het die bron van befondsing nie meerderheid van die uitkomste in die guns van die borge se produkte beïnvloed nie. Meer nie-industrie befondsde navorsing is nodig om verder die impak van befondsing op kliniese uitkomste en skrywers se gevolgtrekkings te evalueer. Beskrywende studie: Aangesien al die maatskappy deelname geweier het, kon geen gevolgtrekking gemaak word of die voedsel bedryf bewyse oor die gebruik van probiotika, prebiotika of synbiotika toepas nie. Meer deursigtigheid is nodig van die formule vervaardigers oor hoe hulle die bewyse oor die gebruik van probiotika, prebiotika of synbiotika toepas.

Objetivos: O presente trabalho é secundário a um estudo clínico randomizado, que teve por objetivos investigar os efeitos de uma substância simbiótica sobre a permeabilidade intestinal, a inflamação sistêmica, a cognição e sintomas depressivos em idosos. Métodos: quarenta e nove participantes, 65-90 anos de idade, ambos os gêneros, foram randomizados em dois grupos: grupo S (uso de simbióticos); e grupo P (uso de placebo). As seguintes avaliações foram realizadas no início e no final do experimento: Escala de Depressão Geriátrica (GDS-15); Mini Exame do Estado Mental (MEEM); % de gordura corporal (%gordura); citocinas pró-inflamatórias e regulatórias no soro (IL-6, TNF-α e IL-10); e marcadores de permeabilidade intestinal no soro (DAO, IFABP e LPS). Resultados: A interação entre tempo e grupo mostrou maior redução do LPS no grupo P e maior aumento do IL-10 no grupo S. Considerando somente o fator tempo, ambos os grupos reduziram a %gordura, TNF-α e DAO. O IL-6, o GDS-15 e MEEM aumentaram em ambos os grupos. O valor final de GDS-15 foi explicado negativamente por DAO, IL-10, TNF-α, %gordura, ser mulher e estar alocado no grupo P. As variáveis que explicaram positivamente o valor final do GDS-15 foram IL-6, IFABP, e LPS. As variáveis positivamente associadas aos valores finais do MEEM foram IL-10, DAO, ser mulher e estar alocado no grupo P; foram encontradas associações negativas entre o MEEM e IL-6, TNF-α, %gordura, IFABP e LPS. Foi discutida a possibilidade de alguma interferência dos medicamentos utilizados pelos idosos, nas variáveis de interesse do estudo. Conclusões: de acordo com nossas condições experimentais, foram encontrados efeitos sutis da suplementação de simbióticos sobre sintomas depressivos e cognição em idosos da comunidade, aparentemente saudáveis; entretanto, os efeitos sobre a cognição parecem ter sido mais otimistas. Estudos futuros, com indivíduos com diagnóstico de depressão ou de comprometimento cognitivo, poderão clarear questões levantadas no presente estudo. / Objectives: This secondary study from a randomized clinical trial aimed to investigate the effect of a synbiotic substance on intestinal permeability, systemic inflammation, cognition and depressive symptoms in elderly. Methods: Forty-nine participants, 65-90 years old, both genders, were randomly assigned into two groups: S-group (synbiotic); and P-group (placebo). Evaluations performed at the beginning and at the end of the experiment were: Geriatric Depressive Symptoms scale (GDS-15); Mini-Mental Status Examination (MMSE); % of body fat (%fat); pro-inflammatory and regulatory cytokines (serum IL-6, TNF-α and IL-10); gut permeability (serum DAO, IFABP and LPS). Results: The interaction between time and group showed higher reduction of LPS in P-group and higher increase of IL-10 in S-group. Considering only time, both groups had reduced their %Fat, TNF-α and DAO. The IL-6, GDS-15 and MMSE were increased in both groups. The GDS-15 final was negatively explained by DAO, IL-10, TNF-α, %Fat, being woman and being allocated in P-group. The variables that positively explained the GDS-15final were the IL-6, the IFABP, and the LPS. The variables that were positively associated to MMSE final were the IL-10, DAO, being woman, and being allocated in P-group; The negative associations were IL-6, TNF-α, %Fat, IFABP and LPS. We discussed the possibility of some interference of the medicines used by the elderly on our outcomes of interest. Conclusions: our experimental conditions demonstrated weak effects of synbiotic supplementation in the management of depressive symptoms or cognitive decline in apparently healthy elderly living in the community, although the effect on cognition seems to be more optimist. Other comparative studies, with individuals diagnosed as depressive morbidity or cognitive decline, may clarify our hypothesis.

Objetivos: O presente trabalho é secundário a um estudo clínico randomizado, que teve por objetivos investigar os efeitos de uma substância simbiótica sobre a permeabilidade intestinal, a inflamação sistêmica, a cognição e sintomas depressivos em idosos. Métodos: quarenta e nove participantes, 65-90 anos de idade, ambos os gêneros, foram randomizados em dois grupos: grupo S (uso de simbióticos); e grupo P (uso de placebo). As seguintes avaliações foram realizadas no início e no final do experimento: Escala de Depressão Geriátrica (GDS-15); Mini Exame do Estado Mental (MEEM); % de gordura corporal (%gordura); citocinas pró-inflamatórias e regulatórias no soro (IL-6, TNF-α e IL-10); e marcadores de permeabilidade intestinal no soro (DAO, IFABP e LPS). Resultados: A interação entre tempo e grupo mostrou maior redução do LPS no grupo P e maior aumento do IL-10 no grupo S. Considerando somente o fator tempo, ambos os grupos reduziram a %gordura, TNF-α e DAO. O IL-6, o GDS-15 e MEEM aumentaram em ambos os grupos. O valor final de GDS-15 foi explicado negativamente por DAO, IL-10, TNF-α, %gordura, ser mulher e estar alocado no grupo P. As variáveis que explicaram positivamente o valor final do GDS-15 foram IL-6, IFABP, e LPS. As variáveis positivamente associadas aos valores finais do MEEM foram IL-10, DAO, ser mulher e estar alocado no grupo P; foram encontradas associações negativas entre o MEEM e IL-6, TNF-α, %gordura, IFABP e LPS. Foi discutida a possibilidade de alguma interferência dos medicamentos utilizados pelos idosos, nas variáveis de interesse do estudo. Conclusões: de acordo com nossas condições experimentais, foram encontrados efeitos sutis da suplementação de simbióticos sobre sintomas depressivos e cognição em idosos da comunidade, aparentemente saudáveis; entretanto, os efeitos sobre a cognição parecem ter sido mais otimistas. Estudos futuros, com indivíduos com diagnóstico de depressão ou de comprometimento cognitivo, poderão clarear questões levantadas no presente estudo. / Objectives: This secondary study from a randomized clinical trial aimed to investigate the effect of a synbiotic substance on intestinal permeability, systemic inflammation, cognition and depressive symptoms in elderly. Methods: Forty-nine participants, 65-90 years old, both genders, were randomly assigned into two groups: S-group (synbiotic); and P-group (placebo). Evaluations performed at the beginning and at the end of the experiment were: Geriatric Depressive Symptoms scale (GDS-15); Mini-Mental Status Examination (MMSE); % of body fat (%fat); pro-inflammatory and regulatory cytokines (serum IL-6, TNF-α and IL-10); gut permeability (serum DAO, IFABP and LPS). Results: The interaction between time and group showed higher reduction of LPS in P-group and higher increase of IL-10 in S-group. Considering only time, both groups had reduced their %Fat, TNF-α and DAO. The IL-6, GDS-15 and MMSE were increased in both groups. The GDS-15 final was negatively explained by DAO, IL-10, TNF-α, %Fat, being woman and being allocated in P-group. The variables that positively explained the GDS-15final were the IL-6, the IFABP, and the LPS. The variables that were positively associated to MMSE final were the IL-10, DAO, being woman, and being allocated in P-group; The negative associations were IL-6, TNF-α, %Fat, IFABP and LPS. We discussed the possibility of some interference of the medicines used by the elderly on our outcomes of interest. Conclusions: our experimental conditions demonstrated weak effects of synbiotic supplementation in the management of depressive symptoms or cognitive decline in apparently healthy elderly living in the community, although the effect on cognition seems to be more optimist. Other comparative studies, with individuals diagnosed as depressive morbidity or cognitive decline, may clarify our hypothesis.

A associação de ingredientes prebióticos com microrganismos probióticos na elaboração de produtos lácteos pode resultar na obtenção de produtos simbióticos, com os efeitos benéficos dos probióticos, aliado ao estímulo seletivo das bifidobactérias endógenas do cólon. Objetivou-se desenvolver um queijo petit-suisse simbiótico, suplementado com os probióticos Lactobacillus acidophilus e Bifidobacterium lactis e os prebióticos inulina, oligofrutose e mel; avaliar a viabilidade dos probióticos e do starter, a concentração de frutanos, a aceitabilidade sensorial e parâmetros físico-químicos durante o seu armazenamento a 4±1°C por até 28 dias; otimizar as misturas envolvendo os prebióticos, garantindo a boa viabilidade probiótica e o potencial efeito prebiótico, associados a características tecnológicas e sensoriais satisfatórias. Para esse fim, foram desenvolvidas formulações de queijo petit-suisse, com Lactobacillus acidophilus e Bifidobacterium lactis, utilizando Streptococcus thermophilus como starter, conforme o delineamento da superfície de resposta para misturas com três fatores: oligofrutose, inulina e mel. Os fatores foram combinados em diferentes proporções, de modo a obter 10% da formulação final, totalizando 7 ensaios e um controle (T1 a T8). As populações dos probióticos estiveram sempre superiores ao recomendado para a promoção dos efeitos benéficos, tendo variado de 7,20 a 7,69 log ufc g-1 (B. lactis) e de 6,08 a 6,99 log ufc g-1 (L. acidophilus). Os valores de pH decresceram e de acidez cresceram ao longo do tempo, devido à atividade dos microrganismos acidificantes presentes, tendo diferido significativamente entre os ensaios (p<0,05). A umidade permaneceu estável e diferiu significativamente entre os ensaios (p<0,05). O ingrediente que mais afetou a textura instrumental foi a inulina, fornecendo produtos mais firmes, mais coesos e com adesividade e gomosidade maiores. Oligofrutose e mel, como ingredientes únicos, produziram queijo petit-suisse com menor firmeza, adesividade e gomosidade, parâmetros estes correlacionados negativamente com o pH nos diferentes produtos estudados, ao contrário do que ocorreu com a coesividade. Os ensaios não diferiram significativamente quanto à aceitabilidade sensorial com painel de consumidores, exceto aos 28 dias de armazenamento (p<0,05). Aqueles contendo oligofrutose (T1) e oligofrutose mais inulina (T4) foram os mais bem aceitos, enquanto o controle (T8) foi o menos aceito. Todos os resultados ficaram entre \"gostei ligeiramente\" e \"gostei moderadamente\". A aceitabilidade foi crescente durante o armazenamento, significativamente (p<0,05) apenas para os ensaios que continham oligofrutose ou inulina sozinhos e sua combinação. Os atributos mais citados pelos consumidores foram o sabor - mais preferido nos ensaios T1 (oligofrutose), T3 (mel) e T5 (oligofrutose mais mel) e menos preferido no T8 (controle), e a textura, sempre menos preferida, em virtude de \"arenosidade\". Todas as combinações dos ensaios estudadas, exceto o T3 (mel), podem ser consideradas prebióticas, partindo-se da recomendação de 4 a 5 g dia-1 de frutanos e com uma porção diária de 100 g de queijo petit-suisse. A Metodologia da Superfície de Resposta aplicada para otimizar a viabilidade dos probióticos, a firmeza instrumental, o teor de frutanos e o custo, resultou na mistura ótima contendo 25% de oligofrutose, 70% de inulina e 5% de mel e desejabilidade global de 99,55%. / Due to the potential synergy between probiotics and prebiotics, dairy products containing a combination of these ingredients are often referred to as synbiotic, providing the beneficial effects of the probiotics combined with the effect of selectively stimulating the growth and/or activity of bifidobacterium in the colon. The purpose of this study was to develop a synbiotic petit-suisse cheese, supplemented with the probiotics Lactobacillus acidophilus and Bifidobacterium lactis and the prebiotics inulin, oligofructose and honey; to monitor the viability of the probiotics and the starter, the concentration of fructans, and also the sensory acceptance and physico-chemical parameters during refrigerated storage (4±1°C) for up to 28 days; to optimize the mixtures involving the prebiotic ingredients, in order to guarantee good probiotic viability and potential prebiotic effects, together with to satisfactory technological and sensory properties. The formulations were developed according to the surface response methodology for mixtures including three factors: oligofructose, inulin and honey. The prebiotics were combined in different proportions (to achieve 10% of total mixture), and 7 trials plus a control trial were obtained (T1 to T8). Probiotic populations were always above the minimum counts suggested for providing health benefits, and varied from 7.20 up to 7.69 log cfu g-1 (B. lactis) and from 6.08 up to 6.99 log cfu g-1 (L. acidophilus). The pH values decreased and the acidity values increased significantly during storage, and were statistically different in the various trials (P<0.05), due to the acidifying effect of the organisms present. The moisture remained stable during storage and also varied statistically in the trials (P<0.05). Instrumental texture profile was greatly influenced by inulin, resulting in firmer, more cohesive and adhesive products, and with higher gumminess. Oligofructose and honey added as sole ingredients produced a less firm, adhesive and gummy cheese. The pH influenced the instrumental firmness, adhesiveness and gumminess negatively, and cohesiveness positively. There was no significant difference in sensory acceptance for the consumer panel between the different trials, except after 28 days of storage (P<0.05). The acceptance was significantly higher for cheeses supplemented with oligofructose (T1) and oligofructose plus inulin (T4), whereas the control (T8) was less accepted. The results always ranged from like slightly to like moderately. Acceptability increased during storage, though significantly (P<0.05) only for cheeses supplemented with oligofructose and/or inulin. Taste was the most preferred attribute for trials T1 (oligofructose), T3 (honey), and T5 (oligofructose plus honey) and less preferred for T8 (control). Texture attribute was always the least preferred, due to the \"dust\" present. All cheese trials, except T3 (honey), can be considered prebiotic, according to the recommended ingestion of 4 to 5 g day -1 of fructans for a 100g daily portion. The response surface methodology, applied to optimize probiotic viability, instrumental firmness, fructans content and cost, resulted in an optimum mixture containing 25% oligofructose, 70% inulin and 5% honey and global desirability of 99.55%.

A associação de ingredientes prebióticos com microrganismos probióticos na elaboração de produtos lácteos pode resultar na obtenção de produtos simbióticos, com os efeitos benéficos dos probióticos, aliado ao estímulo seletivo das bifidobactérias endógenas do cólon. Objetivou-se desenvolver um queijo petit-suisse simbiótico, suplementado com os probióticos Lactobacillus acidophilus e Bifidobacterium lactis e os prebióticos inulina, oligofrutose e mel; avaliar a viabilidade dos probióticos e do starter, a concentração de frutanos, a aceitabilidade sensorial e parâmetros físico-químicos durante o seu armazenamento a 4±1°C por até 28 dias; otimizar as misturas envolvendo os prebióticos, garantindo a boa viabilidade probiótica e o potencial efeito prebiótico, associados a características tecnológicas e sensoriais satisfatórias. Para esse fim, foram desenvolvidas formulações de queijo petit-suisse, com Lactobacillus acidophilus e Bifidobacterium lactis, utilizando Streptococcus thermophilus como starter, conforme o delineamento da superfície de resposta para misturas com três fatores: oligofrutose, inulina e mel. Os fatores foram combinados em diferentes proporções, de modo a obter 10% da formulação final, totalizando 7 ensaios e um controle (T1 a T8). As populações dos probióticos estiveram sempre superiores ao recomendado para a promoção dos efeitos benéficos, tendo variado de 7,20 a 7,69 log ufc g-1 (B. lactis) e de 6,08 a 6,99 log ufc g-1 (L. acidophilus). Os valores de pH decresceram e de acidez cresceram ao longo do tempo, devido à atividade dos microrganismos acidificantes presentes, tendo diferido significativamente entre os ensaios (p<0,05). A umidade permaneceu estável e diferiu significativamente entre os ensaios (p<0,05). O ingrediente que mais afetou a textura instrumental foi a inulina, fornecendo produtos mais firmes, mais coesos e com adesividade e gomosidade maiores. Oligofrutose e mel, como ingredientes únicos, produziram queijo petit-suisse com menor firmeza, adesividade e gomosidade, parâmetros estes correlacionados negativamente com o pH nos diferentes produtos estudados, ao contrário do que ocorreu com a coesividade. Os ensaios não diferiram significativamente quanto à aceitabilidade sensorial com painel de consumidores, exceto aos 28 dias de armazenamento (p<0,05). Aqueles contendo oligofrutose (T1) e oligofrutose mais inulina (T4) foram os mais bem aceitos, enquanto o controle (T8) foi o menos aceito. Todos os resultados ficaram entre \"gostei ligeiramente\" e \"gostei moderadamente\". A aceitabilidade foi crescente durante o armazenamento, significativamente (p<0,05) apenas para os ensaios que continham oligofrutose ou inulina sozinhos e sua combinação. Os atributos mais citados pelos consumidores foram o sabor - mais preferido nos ensaios T1 (oligofrutose), T3 (mel) e T5 (oligofrutose mais mel) e menos preferido no T8 (controle), e a textura, sempre menos preferida, em virtude de \"arenosidade\". Todas as combinações dos ensaios estudadas, exceto o T3 (mel), podem ser consideradas prebióticas, partindo-se da recomendação de 4 a 5 g dia-1 de frutanos e com uma porção diária de 100 g de queijo petit-suisse. A Metodologia da Superfície de Resposta aplicada para otimizar a viabilidade dos probióticos, a firmeza instrumental, o teor de frutanos e o custo, resultou na mistura ótima contendo 25% de oligofrutose, 70% de inulina e 5% de mel e desejabilidade global de 99,55%. / Due to the potential synergy between probiotics and prebiotics, dairy products containing a combination of these ingredients are often referred to as synbiotic, providing the beneficial effects of the probiotics combined with the effect of selectively stimulating the growth and/or activity of bifidobacterium in the colon. The purpose of this study was to develop a synbiotic petit-suisse cheese, supplemented with the probiotics Lactobacillus acidophilus and Bifidobacterium lactis and the prebiotics inulin, oligofructose and honey; to monitor the viability of the probiotics and the starter, the concentration of fructans, and also the sensory acceptance and physico-chemical parameters during refrigerated storage (4±1°C) for up to 28 days; to optimize the mixtures involving the prebiotic ingredients, in order to guarantee good probiotic viability and potential prebiotic effects, together with to satisfactory technological and sensory properties. The formulations were developed according to the surface response methodology for mixtures including three factors: oligofructose, inulin and honey. The prebiotics were combined in different proportions (to achieve 10% of total mixture), and 7 trials plus a control trial were obtained (T1 to T8). Probiotic populations were always above the minimum counts suggested for providing health benefits, and varied from 7.20 up to 7.69 log cfu g-1 (B. lactis) and from 6.08 up to 6.99 log cfu g-1 (L. acidophilus). The pH values decreased and the acidity values increased significantly during storage, and were statistically different in the various trials (P<0.05), due to the acidifying effect of the organisms present. The moisture remained stable during storage and also varied statistically in the trials (P<0.05). Instrumental texture profile was greatly influenced by inulin, resulting in firmer, more cohesive and adhesive products, and with higher gumminess. Oligofructose and honey added as sole ingredients produced a less firm, adhesive and gummy cheese. The pH influenced the instrumental firmness, adhesiveness and gumminess negatively, and cohesiveness positively. There was no significant difference in sensory acceptance for the consumer panel between the different trials, except after 28 days of storage (P<0.05). The acceptance was significantly higher for cheeses supplemented with oligofructose (T1) and oligofructose plus inulin (T4), whereas the control (T8) was less accepted. The results always ranged from like slightly to like moderately. Acceptability increased during storage, though significantly (P<0.05) only for cheeses supplemented with oligofructose and/or inulin. Taste was the most preferred attribute for trials T1 (oligofructose), T3 (honey), and T5 (oligofructose plus honey) and less preferred for T8 (control). Texture attribute was always the least preferred, due to the \"dust\" present. All cheese trials, except T3 (honey), can be considered prebiotic, according to the recommended ingestion of 4 to 5 g day -1 of fructans for a 100g daily portion. The response surface methodology, applied to optimize probiotic viability, instrumental firmness, fructans content and cost, resulted in an optimum mixture containing 25% oligofructose, 70% inulin and 5% honey and global desirability of 99.55%.

Hintergrund: Gestillte Kinder haben im Vergleich zu nicht gestillten Kindern eine geringere Inzidenz von gastrointestinalen Infektionen und atopischen Erkrankungen. Man geht davon aus, dass der gesundheitsfördernde Effekt der Muttermilch teilweise über die intestinale Mikrobiota vermittelt wird. Diese ist in Stillkindern durch eine geringe Diversität und einen hohen Anteil an Bifidobakterien charakterisiert. Neueste Ansätze in der Weiterentwicklung industriell hergestellter Säuglingsnahrung zielen darauf ab, eine intestinale Mikrobiota zu fördern, die der von gestillten Kindern ähnelt. Die Supplementation von Säuglingsnahrung mit Probiotika (lebende Mikroorganismen) oder Präbiotika (unverdauliche Kohlenhydrate, die als Energiesubstrat für probiotische Bakterien dienen) könnte die bifidogene und antipathogene, aber auch immunmodulierende Wirkung der Muttermilch nachahmen. Aufgrund unterschiedlicher Interaktionen mit der Darmmikrobiota und dem Immunsystem fokussiert man mit der gleichzeitigen Gabe von Pro- und Präbiotika (Synbiotika) eine synergistische Wirkung an. Zielstellung und Studiendesign: In einer randomisiert-kontrollierten, klinischen Studie wurde untersucht, ob sich in den ersten drei Lebensmonaten von gesunden und termingerecht geborenen Kindern mit einer Synbiotikum-haltigen Säuglingsnahrung eine intestinale Mikrobiota etabliert, die der von gestillten Kindern gleicht. Das Synbiotikum setzte sich aus Bifidobacterium animalis ssp. lactis CNCM I 3446 (ältere Bezeichnung B. lactis BB-12) und Kuhmilcholigosacchariden zusammen. Die Studie umfasste zwei Gruppen von Kindern, die eine Säuglingsnahrung mit (SYN-Gruppe, n=21) oder ohne Supplement (KON-Gruppe, n=18) erhielten. Gestillte Kinder dienten als Referenz (REF-Gruppe, n=23). Um die Diversität der Bifidobakterien auf Speziesebene umfassend zu charakterisieren, wurden quantitative Real-Time PCR (qPCR)-Verfahren, basierend auf dem single-copy groEL als phylogenetisches Zielgen, zur spezifischen Quantifizierung von zwölf Bifidobakterienspezies in humanen Fäzes entwickelt und validiert. Ergebnisse: Die supplementierte Säuglingsnahrung war gut verträglich und unterstützte eine gesunde Entwicklung; vergleichbare anthropometrische Daten von SYN- und REF-Gruppe. Das Synbiotikum stimulierte selektiv das Wachstum von Laktobazillen und Bifidobakterien. Die Zellzahl für Laktobazillen der SYN-Gruppe war zur REF-Gruppe äquivalent (9,07±0,32 versus 9,90±0,27 log10 Zellen/g Fäzes TM [MW±SEM]; p<0,0019; Äquivalenzdifferenz von 1 log10 Zellen/g Fäzes TM) und höher als in der KON-Gruppe (8,27±0,31 log10 Zellen/g Fäzes TM [MW±SEM]). Die Zellzahl für Bifidobakterien war in der SYN-Gruppe am höchsten (11,54±0,05 versus 11,00±0,17 [REF-Gruppe] und 10,54±0,24 [KON-Gruppe] log10 Zellen/g Fäzes TM [MW±SEM]). In der SYN-Gruppe wurde die höchste Anzahl an Bifidobakterienspezies erfasst (167 mit [128 ohne] B. animalis in 56 Fäzesproben versus 98 und 93 in jeweils 51 Fäzesproben der REF- und KON-Gruppe). Neben Kinder-typischen Spezies wie B. bifidum und B. breve wurden auch Spezies, die für Erwachsene charakteristisch sind (B. adolescentis), häufiger in der SYN-Gruppe als in den Vergleichsgruppen nachgewiesen. Der pH-Wert in Fäzes von Kindern aus der SYN-Gruppe war niedriger als der aus der KON-Gruppe (6,07±0,20 versus 6,45±0,17 [MW±SEM]) und näher an dem von gestillten Kindern mit 5,29±0,12 (MW±SEM). Schlussfolgerung: Die Supplementation einer Säuglingsnahrung mit dem Synbiotikum aus CNCM I-3446 und Kuhmilcholigosacchariden führte zu einer Angleichung in der Zusammensetzung der intestinalen Mikrobiota und des fäkalen pH-Wertes an gestillte Kinder. Die in dieser Arbeit entwickelten groEL-basierten qPCR-Verfahren erlaubten eine spezifische und genaue Analyse der Bifidobakterienpopulation unter dem Einfluss eines Synbiotikums. / Background: Compared to formula-fed infants, breast-fed infants have a reduced incidence of gastrointestinal infections and atopic diseases. The health-promoting effect of breast milk is assumed to be partly mediated by the intestinal microbiota, which is characterized by a low diversity and a high proportion of bifidobacteria. Recent approaches in further development of infant formulae aim at promoting an intestinal microbiota similar to that of breast-fed infants. The supplementation of infant formula with probiotics (live microorganisms) or prebiotics (non-digestible carbohydrates, which serves as energy substrates for probiotic bacteria) could mimic the bifidogenic and antipathogenic, but also immunomodulating effect of breast milk. Due to various interactions with the gut microbiota and the immune system, the simultaneous administration of pro- and prebiotics (synbiotics) is focussed to have a synergistic effect. Objective and study design: In a randomized-controlled, clinical trial healthy full-term infants receiving an infant formula with synbiotic for the first three months of life were studied, whether an intestinal microbiota is induced, which is equivalent to that of breast-fed infants. The synbiotic consisted of Bifidobacterium animalis ssp. lactis CNCM I 3446 (previously known as B. lactis BB-12) and cow milk oligosaccharides. The study comprised two groups of infants receiving a starter formula with (SYN-group, n=21) or without supplement (KON-group, n=18). Breast-fed infants served as a reference (REF-group, n=23). In order to comprehensively characterize the bifidobacteria diversity at species level, quantitative real-time PCR (qPCR) assays based on the single-copy groEL as phylogenetic marker for the specific quantification of twelve bifidobacteria species in human feces were established and validated. Results: The supplemented formula was well tolerated and supported a healthy development; comparable anthropometric data of SYN- and REF-group. The synbiotic selectively stimulated the growth of lactobacilli and bifidobacteria. Lactobacilli levels were equivalent in SYN- and REF-group (9.07±0.32 versus 9.90±0.27 log10 cells/g feces DM [Mean±SEM]; p<0.0019; equivalence margin of 1 log10 cells/g feces DM) and higher than the KON-group (8.27±0.31 log10 cells/g feces DM [Mean±SEM]). The highest levels of bifidobacteria were observed in the SYN-group (11.54±0.05 versus 11.00±0.17 [REF-group] and 10.54±0.24 [KON-group] log10 cells/g feces DM [Mean±SEM]). The highest number of bifidobacteria species were obtained in the SYN-group (167 with [128 without] B. animalis in 56 fecal samples versus 98 and 93 in each of 51 fecal samples of the REF- and KON-group). Beside species, typically found in infants such as B. bifidum und B. breve, also species, which are characteristic for adults (B. adolescentis), were detected more often in the SYN-group than in the other study groups. Fecal pH was lower in the SYN- than in the KON-group 6.07±0.20 versus 6.45±0.17 [Mean±SEM]) and closer to that of breast-fed infants (5.29±0.12 [Mean±SEM]). Conclusion: In infants fed a starter formula supplemented with a synbiotic (CNCM I-3446 and cow milk oligosaccharides), composition of intestinal microbiota and fecal pH were closer to that of breast-fed infants. The groEL-based qPCR-assays, developed in this study, allowed a specific and accurate analysis of the bifidobacterial population in response to the synbiotic intake.

Submitted by Nelci Antunes de Moura (nelcimoura@gmail.com) on 2016-05-20T00:29:22Z No. of bitstreams: 1 tese Nelci final.pdf: 3449766 bytes, checksum: 82850e9746cb84286bf3b3204344f1e9 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-05-23T19:39:07Z (GMT) No. of bitstreams: 1 moura_na_dr_bot.pdf: 3449766 bytes, checksum: 82850e9746cb84286bf3b3204344f1e9 (MD5) / Made available in DSpace on 2016-05-23T19:39:07Z (GMT). No. of bitstreams: 1 moura_na_dr_bot.pdf: 3449766 bytes, checksum: 82850e9746cb84286bf3b3204344f1e9 (MD5) Previous issue date: 2015-12-18 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O ferro heme presente na carne vermelha está associado ao aumento da incidência do câncer colorretal (CCR). O heme pode catalisar a formação de compostos nitrosos e a peroxidação lipídica no lúmen intestinal. No entanto, os efeitos pró-carcinogênicos do heme podem ser inibidos por alguns compostos como os sais de cálcio, clorofila entre outros. Sabe-se que o indol-3-carbinol (I3C), presente nas plantas da família das Brassicas e os simbióticos são compostos promissores na prevenção do câncer de cólon, atuando em via de proliferação, apoptose e modulação da microbiota intestinal. Dessa forma, o objetivo desse estudo foi o de avaliar os efeitos da ingestão de simbiótico (prebiótico inulina associado ao probiótico Bifidobacterium lactis bb-12) e de I3C, isolados ou em associação sobre o processo de carcinogênese de cólon induzido pela 1,2-dimetilhidrazina (DMH) em ratos Wistar alimentados ou não com dieta suplementada com heme. Os animais foram alocados em 9 grupos, os grupos 1 a 8 (n=12) receberam quatro doses de DMH (40 mg/Kg) nas duas semanas iniciais do experimento. Os grupos 1 e 9 (n=12 e 5) receberam ração basal até o final do experimento e os grupos 2 a 8 receberam ração basal suplementada com heme, heme+I3C, heme+simbiótico, heme+I3C+simbiótico, I3C, simbiótico e I3C+simbiótico, respectivamente. A eutanásia ocorreu ao final da 25ª semana. Neste momento foi realizada a coleta do cólon com os respectivos tumores e amostras de fezes do ceco. Em seguida, procedeu-se a medida dos tumores e coleta de amostras para biologia molecular. Após a fixação em formalina tamponada e a retirada dos tumores, realizou-se a contagem de focos de criptas aberrantes (FCA) pela coloração de azul de metileno. Realizou-se a análise histológica dos tumores e a análise da expressão de 95 genes relacionados a via da carcinogênese colônica, pela técnica Taqman Low Density Array, e a expressão proteica da E-caderina, TGFB1 (Transforming growth factor beta 1) e RAF1 (Serine/threonine-protein kinase) por Western Blotting. Foram analisados os índices de proliferação celular e apoptose pelo PCNA (Proliferating cell nuclear antigen) e caspase 3-clivada, respectivamente, tanto nos cólons como em tumores, e a expressão de β-catenina e E-caderina nos tumores, por imunoistoquímica. Células da linhagem Caco-2 foram incubadas com água fecal extraída das fezes do ceco e submetidas a testes de citotoxicidade e genotoxidade pelos testes do MTT (mitochondrial tetrazolium test) e Cometa, respectivamente. Os dados foram comparados utilizando-se o software Sigma Stat 3.5 e Expression Suíte para expressão gênica. Foi observado aumento significativo no número de criptas aberrantes (CA) no grupo que recebeu heme (G2) quando comparado ao grupo que recebeu apenas ração basal (G1). Redução significativa no número de CA foi observada no grupo que recebeu heme+I3C (G3) e heme+simbiótico (G4) quando comparado ao grupo que recebeu heme (G2). O número de FCA totais com ≥ 9 criptas aberrantes foi significativamente menor no grupo que recebeu heme+simbiótico (G4) quando comparado ao grupo que recebeu heme (G2). Entretanto, aumento significativo no número de tumores com mais de 60 mm3 foi observado no grupo suplementado com heme+I3C+simbiótico (G5), quando comparado ao grupo que recebeu heme (G2). Além disso, foi observado aumento significativo na incidência de tumores invasivos no grupo que recebeu heme+I3C+simbiótico (G5) quando comparado ao grupo que recebeu heme (G2). Os tumores do grupo suplementado com heme+I3C+simbiótico (G5) apresentaram baixa expressão dos genes Cdh1, Tgfb1, Appl1 e alta expressão do Raf1, já os tumores do grupo suplementado com heme +I3C (G3) apresentaram baixa expressão do Cdh1. A água fecal do grupo que recebeu heme (G2) apresentou significativamente maior citotoxicidade e genotoxicidade quando comparado ao grupo que recebeu ração basal (G1). Com relação aos tratamentos, a água fecal do grupo que recebeu heme+I3C (G3) e heme e simbiótico (G4) apresentaram água fecal significativamente com menor potencial genotóxico quando comparada ao grupo que recebeu heme (G2). No entanto, o grupo que recebeu heme+I3C+simbiótico (G5) apresentou aumento significativo na genotoxicidade da água fecal. Dessa forma, concluímos que o heme associado a uma dieta com níveis normais de cálcio não é um potente indutor de FCA, mas aumenta a citotoxicidade e genotoxicidade da água fecal. No entanto, tanto o I3C como o simbiótico reduzem os efeitos citotóxicos/genotóxicos da ingestão de heme. Contudo, a associação do heme+I3C+simbiótico apresentou efeito promotor da carcinogênese de cólon. / Colorectal cancer (CRC) is the third most common type of cancer worldwide. Hemin iron, which is found in red meat, catalyzes the formation of carcinogenic N-nitroso compounds and lipid peroxidation end-products in the colon lumen. The procarcinogenic effect of hemin is known to be inhibited by molecules, such as calcium, chlorophyll and others. However, the preventive effect of indole 3-carbinol and synbiotics on colon carcinogenesis remains uninvestigated. The aim of this study was to assess the modifying effects of a synbiotic (inulin+ Bifidobacterium lactis) and/or I3C against dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed male Wistar rats. Nine groups of animals were evaluated. Groups 1–8 received a total of four s.c. DMH injections (40 mg/kg b.w.) over 2 weeks, whereas group 9 was given EDTA solution (vehicle). Two weeks after DMH-initiation, G1 and G9 were fed a basal diet while groups G2, G3, G4, G5, G6, G7 and G8 received a basal diet containing hemin, hemin+I3C, hemin+synbiotic, hemin+I3C+synbiotic, I3C, synbiotic and I3C+synbiotic, respectively, during 23 weeks. At 25 week, all animals were killed and their colons were removed. Cecal contents were collected to determine fecal water cytotoxicity and genotoxicity (DNA damage) in Caco-2 cells. Colon tumors were measured and samples were collected and stored at -800C. The colons were fixed flat in 10% buffered formalin for 24 h and stained with 1.0% methylene blue for classical ACF analysis and quantification. Tumor incidence and multiplicity were assessed after histopathological analysis. Gene and protein expression were determined in tumor samples alone. The total number of aberrant crypts (AC) was significantly higher (p= 0.03) in the hemin group (G2) than in the group fed basal diet (G1). AC number in both hemin+I3C (G3) and hemin+synbiotic (G4) groups was also significantly lower than in the group fed hemin (G2). Tumor volume was higher in the hemin+I3C+ synbiotic (G5) group and invasive adenocarcinoma was more frequent in the hemin+I3C+synbiotic group (G5) than in the group fed hemin (G2). Colon tumor expression analysis showed that in comparison with the group fed hemin (G2), Cdh1, Tgfb1 and Appl1 were downregulated while Raf1 was upregulated in the group hemin+I3C+synbiotic (G5), and Cdh1 was down-regulated in the group hemin+I3C (G3). Fecal water cytotoxicity in the hemin group (G2) was higher than in groups fed basal diet (G1) and hemin+I3C (G3). Fecal water genotoxicity was also significantly higher in the group fed hemin alone (G2) than in the basal diet group (G1), as well as, in groups fed hemin+I3C (G3) and hemin+synbiotics (G4). However, when compared to hemin alone (G2), fecal water from group hemin+I3C+ synbiotics (G5) presented the highest DNA damage levels. Our results suggest that although hemin in a regular-calcium diet was not a powerful ACF promoter, it increased fecal water citotoxicity and genotoxicity. On the other hand, hemin associated with either I3C or synbiotics prevented ACF promotion. Nonetheless, a synergistic interaction among hemin, I3C and synbiotic did promote DMH-induced tumorigenesis. / FAPESP: 2011/23699-4

Orientador: Luís Fernando Barbisan / Resumo: O ferro heme presente na carne vermelha está associado ao aumento da incidência do câncer colorretal (CCR). O heme pode catalisar a formação de compostos nitrosos e a peroxidação lipídica no lúmen intestinal. No entanto, os efeitos pró-carcinogênicos do heme podem ser inibidos por alguns compostos como os sais de cálcio, clorofila entre outros. Sabe-se que o indol-3-carbinol (I3C), presente nas plantas da família das Brassicas e os simbióticos são compostos promissores na prevenção do câncer de cólon, atuando em via de proliferação, apoptose e modulação da microbiota intestinal. Dessa forma, o objetivo desse estudo foi o de avaliar os efeitos da ingestão de simbiótico (prebiótico inulina associado ao probiótico Bifidobacterium lactis bb-12) e de I3C, isolados ou em associação sobre o processo de carcinogênese de cólon induzido pela 1,2-dimetilhidrazina (DMH) em ratos Wistar alimentados ou não com dieta suplementada com heme. Os animais foram alocados em 9 grupos, os grupos 1 a 8 (n=12) receberam quatro doses de DMH (40 mg/Kg) nas duas semanas iniciais do experimento. Os grupos 1 e 9 (n=12 e 5) receberam ração basal até o final do experimento e os grupos 2 a 8 receberam ração basal suplementada com heme, heme+I3C, heme+simbiótico, heme+I3C+simbiótico, I3C, simbiótico e I3C+simbiótico, respectivamente. A eutanásia ocorreu ao final da 25ª semana. Neste momento foi realizada a coleta do cólon com os respectivos tumores e amostras de fezes do ceco. Em seguida, procedeu-se a... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Hemin iron, which is found in red meat, catalyzes the formation of carcinogenic N-nitroso compounds and lipid peroxidation end-products in the colon lumen. The procarcinogenic effect of hemin is known to be inhibited by molecules, such as calcium, chlorophyll and others. However, the preventive effect of indole 3-carbinol and synbiotics on colon carcinogenesis remains uninvestigated. The aim of this study was to assess the modifying effects of a synbiotic (inulin+ Bifidobacterium lactis) and/or I3C against dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed male Wistar rats. Nine groups of animals were evaluated. Groups 1–8 received a total of four s.c. DMH injections (40 mg/kg b.w.) over 2 weeks, whereas group 9 was given EDTA solution (vehicle). Two weeks after DMH-initiation, G1 and G9 were fed a basal diet while groups G2, G3, G4, G5, G6, G7 and G8 received a basal diet containing hemin, hemin+I3C, hemin+synbiotic, hemin+I3C+synbiotic, I3C, synbiotic and I3C+synbiotic, respectively, during 23 weeks. At 25 week, all animals were killed and their colons were removed. Cecal contents were collected to determine fecal water cytotoxicity and genotoxicity (DNA damage) in Caco-2 cells. Colon tumors were measured and samples were collected and stored at -800C. The colons were fixed flat in 10% buffered formalin for 24 h and stained with 1.0% methylene blue for classical ACF analysis and qua... (Complete abstract click electronic access below) / Doutor

De nombreuses pathologies découlent de déséquilibres du microbiote intestinal. Ainsi, des stratégies visent à les prévenir en restaurant cet écosystème par l'apport de probiotiques, de prébiotiques et de synbiotiques. Des résultats prometteurs nécessitant d'être validés rationnellement, nous nous sommes proposés d'établir un premier crible de sélection de bactéries lactiques et de glucooligosaccharides (GOS) pour des activités anti-inflammatoires et anti-prolifératives in vitro. Les probiotiques ont inhibé des pathogènes tout en se révélant résistants aux conditions du tube digestif, tandis que deux GOS ont conduit à leur croissance sélective. De plus, les probiotiques ont réduit la réponse inflammatoire de cellules intestinales et la prolifération de cellules cancéreuses en association avec un GOS. Nous avons donc retenu des produits potentiellement actifs contre les maladies inflammatoires chroniques de l'intestin et du cancer colorectal, par un crible devant être validé in vivo. / Some pathologies are induced by intestinal microbiota disorders. Thus, some strategies aim torestore this ecosystem through probiotics, prebiotics and synbiotics. Promising results need tobe rationally validated, so we aimed to establish the screening first step of lactic acid bacteriaand glucooligosaccharides (GOS) against anti-inflammatory and anti-proliferative activity invitro. Probiotics inhibited pathogens and were resistant to digestive tract conditions whileGOS promoted specifically their growth. Moreover, probiotics reduced inflammatoryresponse of intestinal cells and proliferation of cancer cells when combined with GOS. Thus,we selected compounds potentially efficient against inflammatory bowel diseases andcolorectal cancer, through a screen that need to be validated in vivo