CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8αα T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8αα T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8αα colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system

Probiotics, gut microbiota and their influence on host health and disease

The gastrointestinal tract (GIT) of mammals hosts a high and diverse number of different microorganisms, known as intestinal microbiota. Many probiotics were originally isolated from the GIT, and they were defined by the FAO/WHO as live microorganisms which when administered in adequate amounts confer a health benefit on the host. Probiotics exert their beneficial effects on the host through four main mechanisms: interference with potential pathogens, improvement of barrier function, immunomodulation and production of neurotransmitters, and their host targets vary from the resident microbiota to cellular components of the gut-brain axis. However, in spite of the wide array of beneficial mechanisms deployed by probiotic bacteria, relatively few effects have been supported by clinical data. In this regard, different probiotic strains have been effective in Antibiotic-Associated Diarrhea or Inflammatory Bowel Disease for instance. The aim of this review was to compile the molecular mechanisms underlying the beneficial effects of probiotics, mainly through their interaction with the intestinal microbiota and with the intestinal mucosa. The specific benefits discuss in this paper include among others those elicited directly through dietary modulation of the human gut microbiota.This article is protected by copyright. All rights reservedResearch in our lab is funded by Grants AGL2013-44039R and AGL2013-44761-P from the Spanish “Plan Estatal de I+D+I.” Part of the authors is also partially funded by the [15VI013] Contract-Programme from the University of Vigo and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273). B. S. was recipient of a Ramón y Cajal postdoctoral contract from the Spanish Ministry of Economy and Competitiveness

In silico approach for unveiling the glycoside hydrolase activities in Faecalibacterium prausnitzii through a systematic and integrative large-scale analysis

This work presents a novel in silico approach to the prediction and characterisation of the glycolytic capacities of the beneficial intestinal bacterium Faecalibacterium prausnitzii. Available F. prausnitzii genomes were explored taking the glycolytic capacities of F. prausnitzii SL3/3 and F. prausnitzii L2-6 as reference. The comparison of the generated glycolytic profiles offered insights into the particular capabilities of F. prausnitzii SL3/3 and F. prausnitzii L2-6 as well as the potential of the rest of strains. Glycoside hydrolases were mostly detected in the pathways responsible for the starch and sucrose metabolism and the biosynthesis of secondary metabolites, but this analysis also identified some other potentially interesting, but still uncharacterised activities, such as several hexosyltransferases and some hydrolases. Gene neighbourhood maps offered additional understanding of the genes coding for relevant glycoside hydrolases. Although information about the carbohydrate preferences of F. prausnitzii is scarce, the in silico metabolic predictions were consistent with previous knowledge about the impact of fermentable sugars on the growth promotion and metabolism of F. prausnitzii. So, while the predictions still need to be validated using culturing methods, the approach holds the potential to be reproduced and scaled to accommodate the analysis of other strains (or even families and genus) as well as other metabolic activities. This will allow the exploration of novel methodologies to design or obtain targeted probiotics for F. prausnitzii and other strains of interest.This work was supported by the Spanish "Programa Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad" (Grant AGL2016-78311-R); and, the Asociacion Espanola Contra el Cancer (" Obtencion de peptidos bioactivos contra el Cancer Colo-Rectal a partir de secuencias geneticas de microbiomas intestinales," Grant PS-2016). This work was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER006684). This work was partially supported by the Conselleria de Educacion, Universidades e Formacion Profesional (Xunta de Galicia) under the scope of the strategic funding of ED431C2018/55-GRC Competitive Reference Group.info:eu-repo/semantics/publishedVersio

Le microbiote intestinal : description, rôle et implication physiopathologique

International audienceThe human gut contains 1014 bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real “hidden organ”. In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads.Le microbiote intestinal humain est composé de 1014 bactéries ainsi que d’autres micro-organismes comme les virus, les champignons et les archées. L’étude du microbiote intestinal a dévoilé le rôle fondamental qu’il joue dans la physiologie intestinale mais aussi dans la santé humaine de façon plus générale, comme un véritable« organe caché ». Dans cette revue, nous exposons la structure et le rôle du microbiote intestinal ainsi que son implication en pathologie humaine. Après la colonisation bactérienne du tube digestif chez le nourrisson, la composition du microbiote intestinal est unique à chaque individu bien que plus de 95 % des bactéries le composant puissent être réparties en 4 phyla majeurs. Des approches culture-indépendantes et, plus récemment, l’avènement du séquençage haut débit ont permis de décrire précisément la structure et la diversité du microbiote intestinal ainsi que son altération en pathologie. Le microbiote intestinal est impliqué dans la maturation du système immunitaire et dans de nombreuses voies métaboliques fondamentales comme la fermentation des sucres et des protéines ainsi que le métabolisme des acides biliaires et des xénobiotiques. Le déséquilibre des populations du microbiote intestinal ou dysbiose a des conséquences fonctionnelles importantes et est impliqué dans de nombreuses pathologies digestives (maladies inflammatoires chroniques intestinales, cancer colorectal, etc.) mais aussi dans l’obésité et l’autisme. Ces observations ont conduit à l’émergence de nombreuses études sur les traitements visant à restaurer l’équilibre du microbiote intestinal comme les probiotiques ou la transplantation du microbiote fécal. Mais des travaux récents sur l’activité de métabolites issus du microbiote pourraient conduire à des perspectives thérapeutiques prometteuses

Méliès et l’âge d’or du cinéma forain en France (1896-1914)

« On ne sait guère que c’est sur les champs de foire qu’est né le cinéma, longtemps ambulant […]. Et pourtant, quel meilleur berceau pour l’usine à rêve qu’est le film, que la fête foraine ? ». De retour de Londres où il a appris la prestidigitation, Georges Méliès se produit sur scène dès l’âge de 23 ans, dans un théâtre de la Galerie Vivienne et dans le Cabinet Fantastique du musée Grévin. C’est comme illusionniste qu’il acquiert l’expérience du public, dans un registre spécifique, celui du..

Novel natural parabens produced by a Microbulbifer bacterium in its calcareous sponge host Leuconia nivea

A broad variety of natural parabens, including four novel structures and known ethyl and butyl parabens, were obtained from culture of a Microbulbifer sp. bacterial strain isolated from the temperate calcareous marine sponge Leuconia nivea (Grant 1826). Their structures were elucidated from spectral analysis, including mass spectrometry and 1D and 2D nuclear magnetic resonance. Their antimicrobial activity evaluated against Staphylococcus aureus was characterized by much higher in vitro activity of these natural paraben compounds 3-9 than commercial synthetic methyl and propyl parabens, usually used as antimicrobial preservatives. Compounds 4 and 9 revealed a bacteriostatic effect and compounds 6 and 7 appeared as bactericidal compounds. Major paraben compound 6 was also active against Gram positive Bacillus sp. and Planococcus sp. sponge isolates and was detected in whole sponge extracts during all seasons, showing its persistent in situ production within the sponge. Moreover, Microbulbifer sp. bacteria were visualized in the sponge body wall using fluorescence in situ hybridization with a probe specific to L4-n2 phylotypes. Co-detection in the sponge host of both paraben metabolites and Microbulbifer sp. L4-n2 indicates, for the first time, production of natural parabens in a sponge host, which may have an ecological role as chemical mediators. © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd