Suchergebnisse

The human body is host to a large number of microorganisms which conform the human microbiota, that is known to play an important role in health and disease. Although most of the microorganisms that coexist with us are located in the gut, microbial cells present in other locations (like skin, respiratory tract, genitourinary tract, and the vaginal zone in women) also play a significant role regulating host health. The fact that there are different kinds of microbiota in different body areas does not mean they are independent. It is plausible that connection exist, and different studies have shown that the microbiota present in different zones of the human body has the capability of communicating through secondary metabolites. In this sense, dysbiosis in one body compartment may negatively affect distal areas and contribute to the development of diseases. Accordingly, it could be hypothesized that the whole set of microbial cells that inhabit the human body form a system, and the dialogue between the different host microbiotas may be a contributing factor for the susceptibility to developing diseased states. For this reason, the present review aims to integrate the available literature on the relationship between the different human microbiotas and understand how changes in the microbiota in one body region can influence other microbiota communities in a bidirectional process. The findings suggest that the different microbiotas may act in a coordinated way to decisively influence human well-being. This new integrative paradigm opens new insights in the microbiota field of research and its relationship with human health that should be taken into account in future studies. ; A.V. has been granted by the predoctoral grant provided by the European Union's H2020 research and innovation programme under Marie Sklodowska-Curie grant agreement No801586. (Campus Iberus/UPNA).

This work was supported by Grants from Comisi´on Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2017-84894-R), Junta de Andalucía (CTS-164) with funds from the European Union, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV), Spain. M.T. is a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program). I.R.-V. is a predoctoral fellow of MINECO. The cost of this publication was paid in part with funds from the European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa"). ; Microbiota has a role in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzes whether MMF improves dysbiosis in a genetic model of hypertension. Twenty weeks old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were randomly divided into three groups: untreated WKY, untreated SHR, and SHR treated with MMF for 5 weeks. MMF treatment restored gut bacteria from the phyla Firmicutes and Bacteroidetes, and acetate- and lactate-producing bacteria to levels similar to those found in WKY, increasing butyrate-producing bacteria. MMF increased the percentage of anaerobic bacteria in the gut. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. MMF increased the lower regulatory T cells proportion in mesenteric lymph nodes and Th17 and Th1 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that MMF reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity due to reduced sympathetic drive in the gut associated to the reduced brain neuroinflammation. ; Comision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad SAF201784894R ; Junta de Andalucia CTS-164 ; European Commission ; Spanish Government ; Instituto de Salud Carlos III (CIBERCV) , Spain ; European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa")

In piglets, weaning is a critical event associated with acute social, environmental and dietary stress engendering fairly often post-weaning diarrhea and enterotoxigenic Escherichia coli infections. Current strategies imply the systematic use of antimicrobials now raising public health concerns due to the massive increase of antibiotic resistance genes among bacteria. Non-pharmacological preventive and curative strategies are necessary to fight against post-weaning diarrhea in piglets. In compliance with the European Union directive aiming to reduce, refine and replace the use of animals in research, the principal aim of this PhD project was to develop a new in vitro fermentation model of the weaning piglet colon implemented with mucin beads to simulate both luminal and mucosal microbiota. Following its development and validation towards in vivo data, the presently designed in vitro model was used to evaluate the impact of two of the major stress encountered at weaning: a dietary change and transient anorexia as well as an enterotoxigenic Escherichia coli strain responsible for post-weaning diarrhea on the composition and activity of the microbiota. Finally, the effects of a Saccharomyces live yeast strain to fight against microbiota dysbiosis and ETEC infections in weaning piglets was evaluated using the newly developed in vitro model and cell culture experiments. The data collected throughout this PhD thesis participated to a better understanding of microbiota dysbiosis associated with weaning and gave interesting insights about the interest of a probiotic strategy in the critical period of weaning in piglets. ; Chez les porcelets, le sevrage est une étape cruciale associée avec d'importants stress d'ordres sociaux, environnementaux et alimentaires qui engendrent fréquemment des diarrhées post-sevrage majoritairement d'origine colibacillaire. Actuellement, ces infections sont traitées de manière systématique à l'aide d'antibiotiques. Toutefois, le nombre de bactéries multi-résistantes aux antibiotiques ...

In piglets, weaning is a critical event associated with acute social, environmental and dietary stress engendering fairly often post-weaning diarrhea and enterotoxigenic Escherichia coli infections. Current strategies imply the systematic use of antimicrobials now raising public health concerns due to the massive increase of antibiotic resistance genes among bacteria. Non-pharmacological preventive and curative strategies are necessary to fight against post-weaning diarrhea in piglets. In compliance with the European Union directive aiming to reduce, refine and replace the use of animals in research, the principal aim of this PhD project was to develop a new in vitro fermentation model of the weaning piglet colon implemented with mucin beads to simulate both luminal and mucosal microbiota. Following its development and validation towards in vivo data, the presently designed in vitro model was used to evaluate the impact of two of the major stress encountered at weaning: a dietary change and transient anorexia as well as an enterotoxigenic Escherichia coli strain responsible for post-weaning diarrhea on the composition and activity of the microbiota. Finally, the effects of a Saccharomyces live yeast strain to fight against microbiota dysbiosis and ETEC infections in weaning piglets was evaluated using the newly developed in vitro model and cell culture experiments. The data collected throughout this PhD thesis participated to a better understanding of microbiota dysbiosis associated with weaning and gave interesting insights about the interest of a probiotic strategy in the critical period of weaning in piglets. ; Chez les porcelets, le sevrage est une étape cruciale associée avec d'importants stress d'ordres sociaux, environnementaux et alimentaires qui engendrent fréquemment des diarrhées post-sevrage majoritairement d'origine colibacillaire. Actuellement, ces infections sont traitées de manière systématique à l'aide d'antibiotiques. Toutefois, le nombre de bactéries multi-résistantes aux antibiotiques augmente de façon alarmante et le besoin de stratégies alternatives aux antibiotiques pour lutter contre ces diarrhées post-sevrage devient urgent. En accord avec la directive européenne visant à réduire, remplacer et raffiner le nombre d'animaux utilisés à des fins de recherche, le principal objectif de ce projet de thèse était de développer un modèle in vitro reproduisant les paramètres physicochimiques et microbiens de l'environnement colique du porcelet au sevrage, le MPigut-IVM. Ce système permet, de manière unique, de distinguer les microenvironnements coliques luminaux et mucosaux et leurs microbiotes associés. Une fois validé comparativement à des données in vivo chez le porcelet, ce modèle innovant a été utilisé pour étudier l'effet des principaux stress rencontrés au sevrage, un jeûne alimentaire, suivi d'un changement d'alimentation et d'une infection par une souche d'Escherichia coli entérotoxigénique responsable de diarrhées sur la composition et l'activité du microbiote. Enfin, l'intérêt d'un traitement préventif à base de levures Saccharomyces a été évalué in vitro en utilisant une approche originale combinant le modèle colique développé et des cellules épithéliales intestinales en culture. Les données de cette thèse ont permis à la fois de mieux comprendre l'étiologie de la dysbiose du microbiote observé au sevrage chez les porcelets et d'évaluer in vitro l'intérêt d'une stratégie probiotique lors de cette phase critique de la vie de l'animal.

Diets rich in (poly)phenols are associated with a reduced reduction in the incidence of cardiovascular disorders. While the absorption and metabolism of (poly)phenols has been described, it is not clear how their metabolic fate is affected under pathological conditions. This study evaluated the metabolic fate of berry (poly)phenols in an in vivo model of hypertension as well as the associated microbiota response. Dahl salt-sensitive rats were fed either a low-salt diet (0.26% NaCl) or a high-salt diet (8% NaCl), with or without a berry mixture (blueberries, blackberries, raspberries, Portuguese crowberry and strawberry tree fruit) for 9 weeks. The saltenriched diet promoted an increase in the urinary excretion of berry (poly)phenol metabolites, while the abundance of these metabolites decreased in faeces, as revealed by UPLC¿MS/MS. Moreover, salt and berries modulated gut microbiota composition as demonstrated by 16S rRNA analysis. Some changes in the microbiota composition were associated with the high-salt diet and revealed an expansion of the families Proteobacteria and Erysipelotrichaceae. However, this effect was mitigated by the dietary supplementation with berries. Alterations in the metabolic fate of (poly)phenols occur in parallel with the modulation of gut microbiota in hypertensive rats. Thus, beneficial effects of (poly)phenols could be related with these interlinked modifications, between metabolites and microbiota environments. ; C.B., C.N.d.S., C.O. were funded by ANR (ANR-13-ISV1-0001-01) and FCT (FCTANR/BEX-BCM/0001/2013). D.B. was funded by the Austrian Science Fund (FWF P26127-B20) and European Research Council (Starting Grant: FunKeyGut 741623). D.S. and A.F. acknowledge support from Scottish Government: Rural and Environment Science and Analytical Services. We also acknowledge the Investment for the Future program ANR-11-IDEX-0003-01 within the LABEX ANR-10-LABX-0033 (C.B., C.O.), Fundação para a Ciência e Tecnologia financial support of A.G. (SFRH/BD/103155/2014) and C.N.d.S. (IF/01097/2013). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofounded by FCT through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged.