Search

International audience; Fermentation allows to preserve food in a sustainable way at a lower cost and contributes to the world food security. This method of preservation is currently very popular with a population in search of naturalness. Health virtues are also attributed to fermented foods because they contain living micro-organisms or specific macro- and micronutrients. Are these products, or the fermentation process, as such really beneficial to health?; La fermentation permet de conserver de manière durable les aliments à moindre coût dans de nombreux pays et participe grandement à la sécurité alimentaire mondiale. Ce mode de conservation est actuellement très prisé par une population en recherche de naturalité. Des vertus santé sont également attribuées aux aliments fermentés parce qu’ils contiennent des microorganismes vivants ou des macro-micronutriments spécifiques. Ces produits, très divers, ou le processus de fermentation en tant que tel sont-ils bénéfiques pour la santé ?

Chez les mammifères, la séparation maternelle à la naissance induit un stress chronique avec pour conséquences des altérations comportementales et neurobiologiques. Ainsi, en élevage ovin, les agneaux surnuméraires sont séparés de leur mère à la naissance et nourris avec des laits artificiels, induisant de telles altérations. Des études montrent l’importance du microbiote intestinal sur le développement comportemental. Notre hypothèse est qu’une alimentation enrichie en prébiotique dès la naissance contribuerait, via une action sur le microbiote, à prévenir certains des désordres associés au stress de séparation maternelle, en particulier comportementaux.Des agnelles ont reçu le colostrum de leur mère les 2 jours suivant la naissance avant d’être séparées et nourries avec un lait commercial dépourvu (Preb-) ou enrichi avec un prébiotique (Preb+, 1% galactofructose) jusqu’au sevrage à 7 semaines. Après le sevrage, les agnelles ont toutes reçu une nourriture standard d’élevage. La maturation du microbiote fécal des agnelles a été suivie par séquençage de la région V3-V4 du gène codant l’ARNs 16S à l’âge de 3, 7 et 10 semaines. Parallèlement, leur comportement social a été comparé par une approche éthologique. La position des individus et leurs activités au sein du groupe ont été quantifiées toutes les 10 minutes pendant 3 heures par jour ainsi que les interactions affiliatives et agonistiques, et les vocalisations.Sur la période durant laquelle le galactofructose est apporté par le lait, une restructuration de la composition du microbiote révélant les propriétés bifidogènes du prébiotique est observée : la sur-implantation précoce de 3 espèces de Bifidobactéries au détriment de nombreuses communautés appartenant aux Clostridiales se traduit par une moindre richesse d’espèces dans le groupe Preb+. Elles présentent parallèlement sur le plan comportemental des indices d’association significativement plus importants et des interactions affiliatives plus fréquentes. Elles ont également tendance à manifester moins d’interactions agonistiques et à moins vocaliser. Enfin, les agnelles Preb+ consacrent davantage de temps à consommer du lait sans que ce comportement n’affecte leur croissance.Après le sevrage, une empreinte spécifique du microbiote des agnelles Preb+ est conservée et se caractérise par un meilleur équilibre de l’abondance des espèces présentes, avec notamment, une abondance augmentée des Clostridiales et une meilleure colonisation par Akkermansia muciniphila. Si les différences de comportement social s’estompent après le sevrage, en revanche les agnelles Preb+ présentent un réseau social plus structuré. Enfin, l’intégration de ces données à celles du microbiote par des analyses multidimensionnelles révèle des covariations significatives, mettant ainsi en exergue de potentielles relations entre les modulations du microbiote intestinal et le comportement social lors du développement.En conclusion, l’apport précoce de galactofructose dans le lait diminue durablement les troubles du comportement social des agnelles soumises à un allaitement artificiel et l’absence maternelle. Cette étude suggère que ce prébiotique, via ses répercussions sur la maturation du microbiote intestinal, pourrait compenser certains des effets délétères associés aux stress précoces.

Introduction: Breastfeeding, because of the composition of humain milk, is recommended until six months of the child by the WHO. However, there has been a decrease of exclusive breastfeeding. New artificial milks appear, with a composition trying to get as close as possible to breast milk. Objective: The objective is to identify the effects of prebiotic and / or probiotic supplements in fomula-fed on the health of infantsMethods: Studies comparing groups of formula fed infants to formula fed infants supplemented with prebiotics and / or probiotics were selected from databases (PubMed, Cochrane, Google Scholar)Results: The growth and tolerance studies did not show any significant difference. A decrease in colic and crying is nevertheless reported. A large part of the studies show an improvement in the transit, by the modification of the intestinal flora, less constipation and infectious diarrhea. They also demonstrate an improvement in immunity and a decrease in allergies in children formula fed supplemented with probiotics and/or prebiotics. Conclusion: The effects of milk supplemented with prebiotics are beneficial for the immune system, on the onset of allergies. There are no observed effects on growth and the appearance of side effects. Milks supplemented with probiotics and / or probiotics therefore have beneficial effects compared to standard milk and have no side effects.; Introduction : l’allaitement maternel, de par la composition du lait, est préconisé jusqu’au six mois de l’enfant par l’OMS. Cependant, on observe une baisse de l’allaitement maternel exclusif. De nouveaux laits artificiels apparaissent, avec une composition essayant de se rapprocher au maximum du lait maternel.Objectif : l’objectif est d’identifier les effets des laits supplémentés en prébiotiques et/ou probiotiques sur la santé des nourrissons. Méthodes : des études comparant des groupes de nourrissons nourris au lait artificiel à des nourrissons nourris au lait artificiel supplémentés en prébiotiques et/ou probiotiques ont été sélectionnées sur des bases de données (PubMed, Cochrane, Google Scholar.Résultats : les études sur la croissance et la tolérance n’ont pas vraiment montré de différence significative. Une diminution de coliques et de pleurs est néanmoins constatée. Une grande partie des études démontrent une amélioration du transit, de par la modification de la flore intestinale, moins de constipation et diarrhée. Elles démontrent aussi une amélioration de l’immunité et diminution des allergies chez les enfants nourris au lait supplémentés par les probiotiques et/ou prébiotiques. Conclusion : Les effets des laits supplémentés en prébiotiques sont bénéfiques pour le système immunitaire, sur l’apparition d’allergies. Il n’y a d’effets constatés sur la croissance et l’apparition d’effets indésirables. Les laits supplémentés en probiotiques et/ou probiotique ont donc des effets bénéfiques par rapport aux laits standards et ne présentent pas d’effet indésirables.

Prebiotics are increasingly used as food supplements, especially in infant formulas, to modify the functioning and composition of the microbiota. However, little is currently known about the mechanisms of prebiotic recognition and transport by gut bacteria, while these steps are crucial in their metabolism. In this study, we established a new strategy to profile the specificity of oligosaccharide transporters, combining microbiomics, genetic locus and strain engineering, and state-of-the art metabolomics. We revisited the transporter classification database and proposed a new way to classify these membrane proteins based on their structural and mechanistic similarities. Based on these developments, we identified and characterized, at the molecular level, a fructooligosaccharide transporting phosphotransferase system, which constitutes a biomarker of diet and gut pathology. The deciphering of this prebiotic metabolization mechanism by a nonbeneficial bacterium highlights the controversial use of prebiotics, especially in the context of chronic gut diseases., Prebiotic oligosaccharides, such as fructooligosaccharides, are increasingly being used to modulate the composition and activity of the gut microbiota. However, carbohydrate utilization analyses and metagenomic studies recently revealed the ability of deleterious and uncultured human gut bacterial species to metabolize these functional foods. Moreover, because of the difficulties of functionally profiling transmembrane proteins, only a few prebiotic transporters have been biochemically characterized to date, while carbohydrate binding and transport are the first and thus crucial steps in their metabolization. Here, we describe the molecular mechanism of a phosphotransferase system, highlighted as a dietary and pathology biomarker in the human gut microbiome. This transporter is encoded by a metagenomic locus that is highly conserved in several human gut Firmicutes, including Dorea species. We developed a generic strategy to deeply analyze, in vitro and in cellulo, the specificity and functionality of recombinant transporters in Escherichia coli, combining carbohydrate utilization locus and host genome engineering and quantification of the binding, transport, and growth rates with analysis of phosphorylated carbohydrates by mass spectrometry. We demonstrated that the Dorea fructooligosaccharide transporter is specific for kestose, whether for binding, transport, or phosphorylation. This constitutes the biochemical proof of effective phosphorylation of glycosides with a degree of polymerization of more than 2, extending the known functional diversity of phosphotransferase systems. Based on these new findings, we revisited the classification of these carbohydrate transporters. IMPORTANCE Prebiotics are increasingly used as food supplements, especially in infant formulas, to modify the functioning and composition of the microbiota. However, little is currently known about the mechanisms of prebiotic recognition and transport by gut bacteria, while these steps are crucial in their metabolism. In this study, we established a new strategy to profile the specificity of oligosaccharide transporters, combining microbiomics, genetic locus and strain engineering, and state-of-the art metabolomics. We revisited the transporter classification database and proposed a new way to classify these membrane proteins based on their structural and mechanistic similarities. Based on these developments, we identified and characterized, at the molecular level, a fructooligosaccharide transporting phosphotransferase system, which constitutes a biomarker of diet and gut pathology. The deciphering of this prebiotic metabolization mechanism by a nonbeneficial bacterium highlights the controversial use of prebiotics, especially in the context of chronic gut diseases.

International audience; The aim of this systematic review was to assess the effect of fructo-oligosaccharide supplementation on glucose homeostasis. The search process was based on the selection of publications listed in the Pubmed-Medline database until April 2016 to identify studies evaluating the impact of short-chain fructo-oligosaccharides or oligofructose on glucose homeostasis. Twenty-nine trials were included in the systematic review and the meta-analysis was performed on twelve of these papers according to the inclusion criteria. Fasting blood concentrations of glucose and insulin were selected as pertinent criteria of glucose homeostasis for the meta-analysis. The consumption of fructo-oligosaccharides decreased fasting blood glycaemia levels, whatever the metabolic status (healthy, obese or diabetic) and diet (low-fat or high-fat) throughout the experiment. This reduction was linear with prebiotic dose (from 0 to 13% of the feed). Fasting insulinaemia also decreased linearly with fructo-oligosaccharide supplementation but the reduction was only significant in rodents fed a low-fat diet. Potential underlying mechanisms include gut bacterial fermentation of fructo-oligosaccharides to short-chain fatty acids (SCFA) and bacterial modulation of bile acids, both interacting with host metabolism. This systemic review, followed by the meta-analysis, provides evidence that fructo-oligosaccharide supplementation has a significant effect on glucose homeostasis whatever the health status and diet consumed by animals.

The use of probiotic bacteria derived from fermented foods has been explored by the scientific community as alternative strategies for the treatment of several diseases, mainly regarding intestinal dysfunction. One of the most relevant inflammatory diseases affecting the alimentary tract, for which no current intervention is entirely successful, is mucositis. In this review article, we summarize the most recent proof-of-concept studies dealing with the therapeutic use of dairy origin probiotics, for the treatment of gastrointestinal mucositis. Furthermore, we discuss several approaches for the improvement of the classical therapeutic rationale, such as supplementation with prebiotics and genetic engineering along with the respective translational issues, which may be crucial for the successful transposition of these therapeutic strategies for clinical use.

The influence of feed supplements on behavior and memory has been recently studied in livestock species. However, none of the studies in pigs have investigated supplement effects in the same individuals during different cognitive tests. The objectives of the study were to evaluate the effects of a synbiotic on an episodic-like (Object recognition: OR), a working (Barrier solving: BS) and a long-term (T-maze) memory test. A total of 18 female piglets were supplemented from 1 to 28 days of age with a synbiotic (SYN) containing strains ofLactobacillus, fructo-oligosaccharide and beta-glucan included in chocolate milk, whereas a further 17 only received the chocolate milk (CTL). At weaning (means ± SD; age 18.1±1.8 days, weight 13.8±2.4 kg), they were grouped by 8. A period of habituation in the test arena of 3 successive days (2 trials per day of 5 or 10 min) for the piglets to isolation preceded the OR and BS tests. In farrowing crates, they were exposed for 24 h to an object to chew before the OR test to acclimation to objects. The OR test at 16 days of age tested the ability to remember an object already explored 50 min before. The BS test at 20 days consisted of finding a route through two barriers to join two companion piglets, over five successive trials. The T-maze test between 33 and 41 days consisted of finding a food reward. The test was preceded by another 4 days period of habituation to isolation and learning of the food reward. A total of 9 piglets with no interest for the reward were removed from that test. The test was divided into 2 periods: 6 days of acquisition using the same arm rewarded and 3 days of a reversal stage. The treatment effects were evaluated using ANOVA, with repeated measures for the BS test. Treatment groups had no effect on traits of habituation periods (P>0.1). In the OR test, both treatment groups explored the reference objects and environment the same way (distance travelled, frequency and duration of interaction, P>0.1). SYN piglets interacted quicker with the novel object thanthe CTL piglets (165±116 vs 255±120 s; P0.1). Performances in trial 1 were lowest for all traits (P0.1), except on day 3 of the acquisition stage where SYN piglets were quicker than CTL piglets (13.0±6.2 vs 25.8±18.3 s; P

Perinatal nutrition plays a decisive role in controlling gut bacterial primo-colonization and, thereby, is an important driver of the development and maturation of intestinal immunity. Since a short-chain fructooligosaccharide (scFOS) prebiotic was known to modulate microbiota, our study evaluated effects of such supplementation on intestinal immunity development and functionality of piglets. Sows received a standard diet supplemented with scFOS or not (CTRL) for the last third of gestation and the entire lactation. Intestinal immune system maturation was assessed at PND 21 during lactation. At postnatal day (PND) 28, piglets were weaned on a CTRL or scFOS diet for four to seven weeks. Then, during the post-weaning period, two vaccine challenges were performed individually; one vaccine directed against Influenza respiratory virus and the other directed against the intestinal bacterium Lawsonia intracellularis, to assess immune responsiveness later in life. Maternal scFOS supplementation stimulated the development of the offspring intestinal immune system before weaning. Such improvement induced beneficial effects on its functionality, later in life, by enhancing local defense mechanisms (number of goblet cells and cytokine secretion) and responsiveness to a bacterial vaccine challenge (production of specific antibodies). Interestingly, the maternal scFOS supplementation improved the immune response to L. intracellularis vaccine, but not that to the vaccine directed against the Influenza respiratory virus. The direct scFOS supplementation of weaned piglets increased the response to Influenza challenge, but not to L. intracellularis vaccine. Thus, the window of nutritional exposure to scFOS (maternal versus post-weaning) conditioned the consequences on the immune system. Our results highlight the role played by early prebiotic supplementation to optimize intestinal immune functionality in piglets to obtain health benefits., La nutrition périnatale joue un rôle décisif dans la primo-colonisation bactérienne et constitue un facteur important pour la maturation de l'immunité intestinale. Les fructooligosaccharides à courte chaîne (FOScc) étant des prébiotiques connus pour moduler le microbiote, notre étude a évalué les effets d’une telle supplémentation sur la fonctionnalité du système immunitaire intestinal des porcelets. Des truies ont reçu un régime supplémenté en FOScc ou non (CTRL) en fin de gestation et pendant la lactation. La maturation du système immunitaire intestinal a été évaluée à 21 jours. Au sevrage à 28 jours, la moitié des porcelets de chaque portée a reçu le régime CTRL ou FOScc pendant 4 à 7 semaines. En post-sevrage, deux challenges vaccinaux ont été effectués séparément, un premier vaccin dirigé contre la bactérie intestinale Lawsonia intracellularis et le second contre le virus respiratoire Influenza afin d’évaluer la réactivité immunitaire ultérieure. La supplémentation maternelle en FOScc a stimulé le développement du système immunitaire du porcelet allaité. Une telle amélioration a entraîné des effets bénéfiques sur sa fonctionnalité ultérieure, objectivée par un renforcement des mécanismes de défense (cellules à mucus et sécrétion de cytokines) et de la réponse vaccinale (anticorps spécifiques). La supplémentation maternelle en FOScc a amélioré la réponse immunitaire au vaccin contre L. intracellularis, mais pas celle contre le virus Influenza. La supplémentation directe en FOScc en post-sevrage n’a augmenté que la réponse vaccinale au virus Influenza. Par conséquent, la fenêtre d’exposition nutritionnelle aux FOScc (maternelle versus post-sevrage) conditionne les effets sur le système immunitaire. Nos résultats soulignent le rôle joué par la supplémentation précoce en prébiotiques pour optimiser la fonctionnalité de l’immunité intestinale des porcelets afin d’obtenir des bénéfices sur la santé.

Dans une série d’études menées sur le modèle porcin, nous avons mis en évidence l’impact d’une alimentation déséquilibrée (maternelle ou post-sevrage) durant la période prénatale et/ou postnatale sur la progéniture, en particulier sur la lipidémie et la cholestérolémie plasmatique, l’activité du microbiote intestinal, les comportements et la plasticité neurocognitive, ainsi que le métabolisme et la neurotransmission de zones cérébrales impliquées dans le circuit hédonique et la cognition. Au travers d’études précliniques visant à décrire les effets de traitements pré- ou probiotiques, nous confirmons que des modifications de la composition du microbiote et de son activité métabolique induites par l’alimentation périnatale (alimentation maternelle et formules infantiles) sont durables jusqu’au stade adulte où elles sont également associées à des changements de la physiologie intestinale et du métabolisme de l’adulte. L’alimentation maternelle et du nouveau-né est un levier d’action majeur pour agir via le microbiote sur les réponses comportementales et assurer un développement optimal du nouveau-né et la santé du futur adulte., In a series of studies performed in the pig model, we described the impact of deleterious nutrition (maternal or post-weaning) during the prenatal and/or postnatal period on the progeny, and especially on lipidemia and cholesterolemia, intestinal microbiota activity, the behavior and neurocognitive plasticity, as well as metabolism and neurotransmission in brain areas involved in cognition and reward. Through preclinical studies aimed at describing the effects of pre- or probiotic treatments, we confirmed that the changes in the composition and metabolic activity of the microbiota induced by the perinatal nutrition (maternal diet and infant formula) are persistent until the adult age, where they are associated with changes of intestinal physiology and metabolism. The maternal and newborn nutrition is a major target to act, via the intestinal microbiota, on the behavioral responses and guarantee an optimal neonatal development and adult health.

Dietary factors improving eggshell quality: an updated review with special emphasis on microelements and feed additives . 17. EGGMEAT European Symposium on the Quality of Eggs and Egg Products

International audience

© 2017 American Dairy Science Association Obesity is characterized by altered gut homeostasis, including dysbiosis and increased gut permeability closely linked to the development of metabolic disorders. Milk oligosaccharides are complex sugars that selectively enhance the growth of specific beneficial bacteria in the gastrointestinal tract and could be used as prebiotics. The aim of the study was to demonstrate the effects of bovine milk oligosaccharides (BMO) and Bifidobacterium longum ssp. infantis (B. infantis) on restoring diet-induced obesity intestinal microbiota and barrier function defects in mice. Male C57/BL6 mice were fed a Western diet (WD, 40% fat/kcal) or normal chow (C, 14% fat/kcal) for 7 wk. During the final 2 wk of the study, the diet of a subgroup of WD-fed mice was supplemented with BMO (7% wt/wt). Weekly gavage of B. infantis was performed in all mice starting at wk 3, yet B. infantis could not be detected in any luminal contents when mice were killed. Supplementation of the WD with BMO normalized the cecal and colonic microbiota with increased abundance of Lactobacillus compared with both WD and C mice and restoration of Allobaculum and Ruminococcus levels to that of C mice. The BMO supplementation reduced WD-induced increase in paracellular and transcellular flux in the large intestine as well as mRNA levels of the inflammatory marker tumor necrosis factor α. In conclusion, BMO are promising prebiotics to modulate gut microbiota and intestinal barrier function for enhanced health.

Mounting evidence shows that the gut microbiota, an important player within the gut-brain communication axis, can affect metabolism, inflammation, brain function and behavior. Interestingly, gut microbiota composition is known to be altered in patients with metabolic syndrome (MetS), who also often display neuropsychiatric symptoms. The use of prebiotics, which beneficially alters the microbiota, may therefore be a promising way to potentially improve physical and mental health in MetS patients. This hypothesis was tested in a mouse model of MetS, namely the obese and type-2 diabetic db/db mice, which display emotional and cognitive alterations associated with changes in gut microbiota composition and hippocampal inflammation compared to their lean db/+ littermates. We assessed the impact of chronic administration (8 weeks) of prebiotics (oligofructose) on both metabolic (body weight, food intake, glucose homeostasis) and behavioral (increased anxiety-like behavior and impaired spatial memory) alterations characterizing db/db mice, as well as related neurobiological correlates, with particular attention to neuroinflammatory processes. Prebiotic administration improved excessive food intake and glycemic dysregulations (glucose tolerance and insulin resistance) in db/db mice. This was accompanied by an increase of plasma anti-inflammatory cytokine IL-10 levels and hypothalamic mRNA expression of the anorexigenic cytokine IL-1β, whereas unbalanced mRNA expression of hypothalamic orexigenic (NPY) and anorexigenic (CART, POMC) peptides was unchanged. We also detected signs of improved blood-brain-barrier integrity in the hypothalamus of oligofructose-treated db/db mice (normalized expression of tight junction proteins ZO-1 and occludin). On the contrary, prebiotic administration did not improve behavioral alterations and associated reduction of hippocampal neurogenesis displayed by db/db mice, despite normalization of increased hippocampal IL-6 mRNA expression. Of note, we found a relationship between the effect of treatment on dentate gyrus neurons and spatial memory. These findings may prove valuable for introducing novel approaches to treat some of the comorbidities associated with MetS.

The digestive tract harbours a complex microbial ecosystem specific to each individual, called gut microbiota. Several recent studies have highlighted the influence of this microbiota on the glucidic and lipid metabolisms of its host. In particular, some bacteria are capable of metabolising cholesterol or converting bile acids, and thereby influencing the level of cholesterol in the blood. These studies suggest that gut microbiota is able to modulate the development of atherosclerosis and cardiovascular diseases and that it could in the future constitute a new therapeutic target for preventing or treating these pathologies.; Le tube digestif héberge un écosystème microbien complexe et spécifique à chaque individu, appelé microbiote intestinal. Plusieurs études récentes ont mis en évidence une influence de ce microbiote sur les métabolismes glucidique et lipidique de son hôte. En particulier, certaines bactéries sont capables de métaboliser le cholestérol ou de convertir les acides biliaires, et ainsi d’influencer le taux de cholestérol sanguin. Ces données suggèrent que le microbiote intestinal a la faculté de moduler le développement de l’athérosclérose et des maladies cardiovasculaires et qu’il pourrait dans l’avenir constituer une nouvelle cible thérapeutique pour prévenir ou traiter ces pathologies.

La nutrition périnatale conditionne durablement les fonctions physiologiques, avec des conséquences sur la susceptibilité à développer des maladies métaboliques à l’âge adulte. Le microbiote représente un des acteurs de cette empreinte nutritionnelle. L’objectif est de déterminer chez le porc l’impact d’une supplémentation périnatale en fructo-oligosaccharides à courte chaîne (scFOS) sur le développement des fonctions immunitaires et endocrines intestinales et les conséquences sur la santé métabolique de l’adulte en situation de déséquilibre nutritionnel. La supplémentation maternelle en scFOS, en modifiant le microbiote maternel et de la descendance et la qualité du lait, accélère la maturation du système immunitaire intestinal des porcelets allaités. La fenêtre d’exposition (maternelle vs post-sevrage) conditionne la nature des modifications immunes induites par les scFOS. La supplémentation périnatale en scFOS modifie la réponse métabolique de l’adulte à un régime déséquilibré en stimulant la fonction endocrine intestinale et la sensibilité du pancréas au glucose, en réduisant les risques d’inflammation, et in fine en modifiant l’homéostasie métabolique, associé à des modulations du microbiote. En résumé, la consommation périnatale de prébiotiques programme le phénotype métabolique et immunitaire de l’adulte via des modulations persistantes du microbiote. L'approche intégrée des données a permis d’identifier des acteurs moléculaires impliqués dans l’adaptation différentielle des individus à un régime déséquilibré en fonction de leur alimentation périnatale., Perinatal nutrition durably programs physiologic and metabolic functions, with consequences on the susceptibility to develop metabolic diseases in adulthood. The microbiota represents an actor of such nutritional imprinting. The objective is to determine, in the pig used as human model, the impact of perinatal short-chain fructooligosaccharide (scFOS) supplementation on the development of intestinal immune and endocrine functions, and consequences on metabolic and infl ammatory status in adults submitted to an unbalanced diet. [br/] Maternal scFOS supplementation, modifying the mother nutritional quality of milk, accelerates intestinal immune system maturation of suckling piglets. The exposure window (maternal vs post-weaning) programs differently immune responses induced by scFOS towards different vaccines. Perinatal scFOS supplementation modifi es metabolic response to an unbalanced diet in adults by stimulating intestinal endocrine function and pancreas sensitivity to glucose, by reducing risks of infl ammation, and in fi ne by changing metabolic homeo-stasis in association with modifi cations of microbiota. In summary, prebiotic consumption during perinatal life programs the immune and metabolic phenotype of adults through persistent modulations of intestinal microbiota. The integrated approach of data enables us to identify molecular actors involved in the differential adaptation of individuals to an unbalanced diet according to their perinatal nutrition.

International audience; Imprinting power: early-life supplementation with prebiotic impacts immune system and energy metabolism in pigs subjected to challenge. 5. Beneficial Microbes Conference

Session Scientifique 1 : “Immunomodulation”Session Scientifique 1 : “Immunomodulation”; International audience; Impact of food additive (prebiotic) and food contaminant (mycotoxin) in the maternal diet onto the ontogenesis and responsiveness of mucosal immune system. IAD 2016 - 10. Journées du Réseau Français "Immunologie des animaux domestiques"

Perinatal nutrition, a key factor controlling gut bacterial colonization, may have lasting consequences on health. We investigated whether early short-chain fructooligosaccharide (scFOS) supplementation, known to well-balance microbiota, impacted adult metabolic and immunologic responses to a high-fat (HF) diet. Sows received a supplementation with scFOS or not for the last 4 weeks of gestation and the lactation. The scFOS supplementation was maintained in piglets weaned from scFOS sows till postnatal day (PND) 56. Twenty four piglets were then fed a standard diet until PND190, then a HF diet for 12 weeks. Early scFOS supplementation increased faecal short-chain fatty acid production after 3 weeks of HF diet but this effect was not observed later. Ongoing metagenomics analysis will give more insights on microbiota composition changes. Insulin response to a glucose challenge (IVGTT) tended to increase in scFOS group, but no other metabolic parameter was modified (lipid metabolism, basal glycaemia and insulinemia, insulin pancreatic content). Preliminary results showed a modulation of the pro-inflammatory cytokine secretion (IFNg , TNFa, IL-8) by ex vivo stimulated ileal explants and MLN cells, revealing a modification of local immunity orientation with perinatal scFOS supplementation. Our results underline the key role of early microbiota modulation on adult responses to a nutritional challenge.

International audience; The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.; Le microbiote intestinal est considéré de plus en plus comme un partenaire symbiotique contribuant au bon état de santé général de l’organisme. Les approches métagénomiques, en pleine expansion, permettent de mieux en mieux appréhender la complexité de l’écosystème intestinal et de son impact sur le développement et le fonctionnement du système nerveux central de son hôte. Elles pourraient permettre à l’avenir le développement de thérapeutiques spécifiques ciblant le microbiote intestinal, comme les probiotiques, les prébiotiques et les approches nutritionnelles chez les patients souffrant de troubles mentaux. Ces traitements existent déjà dans le traitement de certaines pathologies intestinales, mais l’efficacité, le type de souches, la quantité et la durée administrée restent à déterminer chez l’humain, alors que les résultats animaux sont très prometteurs dans les modèles de troubles anxieux et de stress chronique. Le but de la présente revue est de synthétiser les données actuelles, d’une part, sur l’association entre la dysbiose du microbiote intestinal et le déclenchement ou l’entretien de troubles psychiatriques, et d’autre part, d’explorer les thérapeutiques potentielles qui pourraient être proposées aux patients souffrant de troubles psychiatriques associés à une dysbiose intestinale.

Probiotics are live microorganisms, which when administered in adequate amounts confer a health benefit on the host. Bacillus probiotic strains are not able to colonize the gut, and are considered as transient residents of the microbiota. Prebiotic are non-digestible food ingredients that could stimulate growth of bacteria in the gut. This work investigates the in vitro effect of a prebiotic isomaltooligosaccharide (IMOS) on the growth of a probiotic strain Bacillus subtilis. This study highlights the ability of the strain to use IMOS as unique carbon source. A comparative proteomic analysis investigates the main enzymes implicated in the prebiotic metabolism, and biomarkers possibly involved in probiotic effects. This preliminary work, which studies the synbiotic association between a probiotic and a prebiotic, will lead to in vivo assays. Beneficial effects of probiotic Bacilli, mainly modulation of intestinal immune system, result from interaction between bacterial cell-wall molecules and intestinal cells. The molecular origin of immunomodulatory mechanisms are poorly understood, while understanding is needed to optimize the use of probiotics. A second part of this work consists in comparing the structure of a molecular cell-wall component named lipoteichoic acids (LTA) from three Bacillus probiotic, a molecular cell-wall component of Gram positive bacteria, and their immunological activity. A structural study, using biochemical determinations and NMR spectroscopic analysis, highlights the structural diversity between LTAs from different Bacillus species. The key role of D-alanine substituents in the biological activity of these bacterial antigens has been demonstrated.; Les probiotiques sont des microorganismes vivants qui, lorsqu’ils sont ingérés en quantité adéquate, peuvent exercer des propriétés bénéfiques sur la santé de l’hôte. Les souches de Bacillus utilisées en tant que probiotiques ne sont pas colonisatrices du tractus intestinal, mais sont des résidents transitoires du microbiote. Ce travail fait l’investigation in vitro de l’association, qualifiée de synbiotique, entre une souche probiotique de Bacillus subtilis et une source carbonée prébiotique, composé alimentaire peu digéré par les enzymes intestinales mais utilisable par les bactéries dans l’intestin. L’étude de cette association met en évidence la capacité de la souche à utiliser les isomaltooligosaccharides (IMOS) prébiotiques comme unique substrat carboné. L’effet positif de ce substrat sur la tolérance à la bile de la souche a été démontré in vitro. Les résultats d’une analyse protéomique faisant l’étude des enzymes clés impliquées dans le métabolisme des IMOS, ainsi que d’autres biomarqueurs d’intérêt probiotique, sont en cours d’exploitation. Ce travail préliminaire d’investigation de l’association synbiotique entre les IMOS prébiotiques et la souche probiotique B. subtilis, aboutira à des essais in vivo. Les effets bénéfiques des probiotiques du genre Bacillus, notamment au niveau de la modulation du système immunitaire, résultent de l’interaction entre les molécules de la surface bactérienne et les cellules de l’intestin. Les mécanismes moléculaires à l’origine de l’immunomodulation sont mal connus, alors que leur compréhension est nécessaire à l’optimisation de l’utilisation du probiotique. Un deuxième volet de ce travail concerne la comparaison des structures d’entités moléculaires de surface de trois Bacilli probiotiques, les acides lipotéichoïques (LTAs), et leurs activités immunologiques respectives. Une étude structurale des LTAs par des méthodes biochimiques et par RMN a permis de mettre en évidence la diversité structurale au sein du même genre Bacillus. Le rôle clé de la D-alanine dans l’activité biologique de ces antigènes bactériens a été démontré.

International audience; Food allergies are increasing, and no treatment exists, thus a strategy to prevent or reduce allergies would consist of modulating the host microbiota using either allochthonous bacteria (probiotics) or nondigestible food ingredients that can regulate the autochthonous microbiota (composition and metabolism), such as prebiotics. This study aimed to analyze the preventive effects of prebiotic feeding during perinatal and postweaning periods in a mouse model of food allergy.

Le côlon ou gros intestin est la partie terminale de notre tube digestif qui est essentiellement dédiée à l’absorption d’eau mais qui se charge aussi de dégrader les composés alimentaires qui n’ont pas été digérés et absorbés en amont dans l’estomac et l’intestin grêle. Ce compartiment digestif est très dense en microorganismes et ce sont eux (et non pas nos propres enzymes) qui métabolisent les résidus alimentaires. En effet, une des principales fonctions de cette communauté microbienne colique, récemment renommée microbiote colique, est de dégrader puis fermenter les fibres alimentaires. Les fibres alimentaires sont des glucides plus ou moins complexes (cellulose, hémicelluloses, pectines, amidon résistant…) et sont retrouvées dans les fruits, les légumes ou les céréales que nous consommons. L’apport de fibres dans notre alimentation a des effets bénéfiques sur notre santé et ces effets sont en grande partie dus à l’activité des microorganismes que nous hébergeons dans notre tube digestif., The colon or large intestine is the distal segment of our digestive tract that is essentially dedicated to water absorption but that also supports the degradation of the food compounds that are not digested and absorbed upstream in the stomach and the small intestine. This digestive compartment is rich in microorganisms, and it is them (and not our own enzymes) that metabolize dietary residues. Indeed, one main function of this colonic microbial community, recently renamed colonic microbiota, is to degrade and ferment dietary fibres. Dietary fibres correspond to more or less complex carbohydrates (cellulose, hemicelluloses, pectins, resistant starch…) that are found in fruits, vegetables and cereals that we consume. The addition of fibres in our diet has several beneficial health effects, and these effects are for a major part due to the activity of the microorganisms that we harbor in our digestive tract.

Prebiotics and probiotics are used for treatment of GI disorders, such inflammatory bowel disease, irritable bowel syndrome, and recently, obesity; these disorders have altered gut microbiota, impaired intestinal barrier function, and inflammation. A synergistic relationship has been shown between prebiotic bovine milk oligosaccharides (BMO) and probiotic Bifidobacterium longum subsp. infantis (B. infantis) in vitro (Garrido et al, Plos One, 2011). The aim of the study was to assess the ability of BMO and B. infantis to restore intestinal permeability in vivo. Mice were fed a western diet (WD, 20% fat) or normal chow (NC, 10% fat) for seven weeks. For the final two weeks of the study, the diet of a subgroup of WD-fed mice was supplemented with BMO (7%). Weekly gavage of B. infantis was performed in all mice starting at week three. The presence of B. infantis was confirmed in the large intestine of all mice at the completion of the study. Intestinal tissue was mounted in Ussing chambers to evaluate intestinal permeability. Ingestion of WD compared to NC increased paracellular and transcellular flux in the large intestine; barrier function was restored by BMO supplementation. mRNA of the inflammatory marker TNFα was lower in intestine of BMO-supplemented compared to WD mice. Conditioned medium from B. infantis+BMO but not from B. infantis+lactose cultures protected against pro-inflammatory cytokine-induced alteration of barrier function in Caco-2 cells. The data support the hypothesis that B. infantis+BMO restores intestinal barrier function, thereby decreasing the passage of detrimental luminal contents causing inflammation.

Rotifers (Brachionus plicatilis), commonly used at first feeding in commercial fish hatcheries, carry a large bacteria load. Because they are relatively poor in essential fatty acids, it is common practice to enrich them with fatty acids, including arachidonic acid (AA). This study aims to determine whether prey enrichment with AA may act as a prebiotic and modify the microbial community composition either in AA-enriched rotifer cultures or in larval-rearing water using winter flounder (Pseudopleuronectes americanus) as a larval fish model. AA enrichment modified the bacterial community composition in both the rotifer culture tanks and the larval-rearing tanks. We observed an increase in the number of cultivable bacteria on TCBS (thiosulfate-citrate-bile salts-sucrose) agar, used as a proxy for the abundance of Vibrio sp. The results suggest that AA may also play an indirect role in larval health., Les rotifères (Brachionus plicatilis), fréquemment utilisés comme première source alimentaire dans les piscicultures commerciales, portent une charge bactérienne importante. Parce qu’ils sont relativement pauvres en acides gras essentiels, il est de pratique courante de les enrichir en acides gras, notamment en acide arachidonique (AA). Cette étude vise à déterminer si l’enrichissement des proies à l’AA peut agir comme prébiotique et modifier la composition de la communauté microbienne non seulement dans les cultures de rotifères enrichies à l’AA, mais aussi dans l’eau d’élevage des larves, en utilisant la plie rouge (Pseudopleuronectes americanus) comme modèle de larves de poisson. L’enrichissement en AA a modifié la composition de la communauté microbienne tant dans les bassins de culture de rotifères que dans les bassins d’élevage des larves. Un accroissement du nombre de bactéries cultivables sur la gélose TCBS (thiosulfate – citrate – sels biliaires – sucrose), utilisée pour estimer l’abondance de Vibrio sp., a également été observé. Les résultats suggèrent que l’AA peut aussi jouer un rôle indirect dans la santé des larves

We read with great interest the recent study by Dewulf and coworkers1 reporting encouraging results on a prebiotic-based dietary intervention trial in obese patients. This work enlightens that even subtle changes in the gut microbiota may influence the metabolomic signature both inside and outside the gut. Interplay among diet, immunity and microbial and host metabolism results in a complex multidirectional signalling that is critical in the maintenance of a healthy gut functionality, reducing risks for inflammatory bowel diseases and metabo-inflammation states associated with obesity.2 ,3 In parallel, the ‘omics’ era has produced many observations associated with disease states,4 and the correlation among the presence, absence or specific ratios of certain bacterial phyla, orders or genera can be considered as a strategy to directly or indirectly manipulate the microbiome. However, a clear causal molecular link between a specific microbial community and a specific metabolic or immune profile is …

National audience

Recent advances in our understanding of the community structure and function of the human microbiome have implications for the potential role of probiotics and prebiotics in promoting human health. A group of experts recently met to review the latest advances in microbiota/microbiome research and discuss the implications for development of probiotics and prebiotics, primarily as they relate to effects mediated via the intestine. The goals of the meeting were to share recent advances in research on the microbiota, microbiome, probiotics, and prebiotics, and to discuss these findings in the contexts of regulatory barriers, evolving healthcare environments, and potential effects on a variety of health topics, including the development of obesity and diabetes; the long-term consequences of exposure to antibiotics early in life to the gastrointestinal (GI) microbiota; lactose intolerance; and the relationship between the GI microbiota and the central nervous system, with implications for depression, cognition, satiety, and mental health for people living in developed and developing countries. This report provides an overview of these discussions.

International audience

International audience

National audience

International audience

Salmonella entericaserovar Typhimurium is a facultative intracellular pathogen that causes inflammation, necrosis, and diarrhea in pigs, as well as being an important source of food-borne diseases in humans. Probiotics and prebiotics are promising alternatives to antibiotics to control and prevent intestinal infections. The present work investigated a recently developed β-galactomannan (βGM) prebiotic compared to the proven probioticSaccharomyces cerevisiaevar.boulardiion porcine ileum intestinal epithelial cells (IECs) of the IPI-2I line and monocyte-derived dendritic cells (DCs) coculturedin vitrowithSalmonella. We observed that bothS. cerevisiaevar.boulardiiand βGM inhibited the association ofSalmonellawith IECsin vitro. Our data indicated that βGM has a higher ability thanS. cerevisiaevar.boulardiito inhibitSalmonella-induced proinflammatory mRNA (cytokines tumor necrosis factor alpha [TNF-α], interleukin-1α [IL-1α], IL-6, and granulocyte-macrophage colony-stimulating factor [GM-CSF] and chemokines CCL2, CCL20, and CXCL8) and at protein levels (IL-6 and CXCL8). Additionally, βGM andS. cerevisiaevar.boulardiiinduced some effects on DCs that were not observed on IECs: βGM andS. cerevisiaevar.boulardiishowed slight upregulation of mRNA for TNF-α, GM-CSF, and CCR7 receptor on porcine monocyte-derived dendritic cells (DCs). Indeed, the addition of βGM orS. cerevisiaevar.boulardiion DCs cocultured withSalmonellashowed higher gene expression (mRNA) for TNF-α, GM-CSF, and CXCL8 compared to that of the control withSalmonella. In conclusion, the addition of βGM inhibitsSalmonella-induced proinflammatory profiles in IECs but may promote DC activation, although associated molecular mechanisms remain to be elucidated.

Source : Etude de l’effet d’un mélange d’oligosaccharides prébiotiques sur le système immunitaire, la barrière intestinale et la prévention d’une allergie, au moyen d’un modèle souris d’allergie au blé. Thèse de Pascal Gourbeyre sous la direction de Sandra Denery et Marie Bodinier (soutenue le 09 novembre 2011); National audience

Ruminococcus gnavus belongs to the 57 most common species present in 90% of individuals. Previously, we identified an α-galactosidase (Aga1) belonging to glycoside hydrolase (GH) family 36 from R. gnavus E1 (M. Aguilera, H. Rakotoarivonina, A. Brutus, T. Giardina, G. Simon, and M. Fons, Res. Microbiol. 163:14–21, 2012). Here, we identified a novel GH36-encoding gene from the same strain and termed it aga2 . Although aga1 showed a very simple genetic organization, aga2 is part of an operon of unique structure, including genes putatively encoding a regulator, a GH13, two phosphotransferase system (PTS) sequences, and a GH32, probably involved in extracellular and intracellular sucrose assimilation. The 727-amino-acid (aa) deduced Aga2 protein shares approximately 45% identity with Aga1. Both Aga1 and Aga2 expressed in Escherichia coli showed strict specificity for α-linked galactose. Both enzymes were active on natural substrates such as melibiose, raffinose, and stachyose. Aga1 and Aga2 occurred as homotetramers in solution, as shown by analytical ultracentrifugation. Modeling of Aga1 and Aga2 identified key amino acids which may be involved in substrate specificity and stabilization of the α-linked galactoside substrates within the active site. Furthermore, Aga1 and Aga2 were both able to perform transglycosylation reactions with α-(1,6) regioselectivity, leading to the formation of product structures up to [Hex] 12 and [Hex] 8 , respectively. We suggest that Aga1 and Aga2 play essential roles in the metabolism of dietary oligosaccharides and could be used for the design of galacto-oligosaccharide (GOS) prebiotics, known to selectively modulate the beneficial gut microbiota.

The fos region of the avian pathogenic Escherichia coli strain BEN2908 is involved in fructan metabolism, prebiotics widely used commercially in food products for both humans and animals. This metabolism contributes to the establishment of BEN2908 in its reservoir, the intestine. The fos region, located within the genomic island AGI-3, is composed of six genes encoding a sugar transporter and enzymes involved in fructan metabolism, and of a divergently transcribed gene encoding a transcriptional regulator, FosR, belonging to the Laci/GalR family. We demonstrated that the expression of fos genes is repressed by FosR, controlled by catabolite repression and induced in the presence of fructans. FosR binds to two operator sequences of the fos operon promoter region. This binding to DNA is inhibited in the presence of fructans, especially by 1-kestose. The fos region strongly benefits growth on cecal content and colonization of the ceca in vivo. Moreover, AGI-3 is mobile and transferable, suggesting a possible dissemination of fructan metabolism within the species E. coli., La région fos de la souche d' Escherichia coli pathogène aviaire BEN2908 permet le métabolisme des fructanes, des prébiotiques largement utilises en alimentation humaine et animale. Ce métabolisme contribue a l'implantation de BEN2908 dans son réservoir, l'intestin. La région fos, située au sein de l'ilot génomique AGI-3, est composée de 6 gènes codant pour un transporteur de sucre et des enzymes impliquées dans le métabolisme des fructanes, et d'un gène transcrit de façon divergente codant pour FosR, un régulateur transcriptionnel de la famille Laci/GalR. Nous avons montre que l' expression des gènes fos est réprimée par FosR, contrôlée par la répression catabolique et induite en présence de fructanes. FosR se lie a 2 séquences opératrices de la région promotrice de l' opéron fos et cette liaison est inhibée en présence de fructanes, surtout par le 1-kestose. La region fos confère un avantage de croissance en présence de contenu caecal et contribue a la colonisation des caeca in vivo. De plus, AGI-3 est mobile et transférable, ce qui suggère une possible diffusion du métabolisme des fructanes au sein de l’espèce E. coli.

National audience

National audience

National audience