A fibrolytic potential in the human ileum mucosal microbiota revealed by functional metagenomic

The digestion of dietary fibers is a major function of the human intestinal microbiota. So far this function has been attributed to the microorganisms inhabiting the colon, and many studies have focused on this distal part of the gastrointestinal tract using easily accessible fecal material. However, microbial fermentations, supported by the presence of short-chain fatty acids, are suspected to occur in the upper small intestine, particularly in the ileum. Using a fosmid library from the human ileal mucosa, we screened 20,000 clones for their activities against carboxymethylcellulose and xylans chosen as models of the major plant cell wall (PCW) polysaccharides from dietary fibres. Eleven positive clones revealed a broad range of CAZyme encoding genes from Bacteroides and Clostridiales species, as well as Polysaccharide Utilization Loci (PULs). The functional glycoside hydrolase genes were identified, and oligosaccharide break-down products examined from different polysaccharides including mixed-linkage β-glucans. CAZymes and PULs were also examined for their prevalence in human gut microbiome. Several clusters of genes of low prevalence in fecal microbiome suggested they belong to unidentified strains rather specifically established upstream the colon, in the ileum. Thus, the ileal mucosa- associated microbiota encompasses the enzymatic potential for PCW polysaccharide degradation in the small intestine

Guide technique Interactions nappe/rivière: Des outils pour comprendre et mesurer les échanges

National audienceLa démarche et les outils présentés dans ce guide permettent de diagnostiquer qualitativement et quantitativement les échanges nappe/rivière en tenant compte du degré plus ou moins élevé d’anthropisation. De tels diagnostics contribueront à la préservation de la ressource en eau, des nappes phréatiques et de la biodiversité aquatique sur les bassins versants à enjeux importants. Ils sont issus de travaux de recherche et applicables en contexte alluvionnaire et sédimentaire. Le guide propose une démarche (parties A et B) qui aidera le lecteur à choisir les outils adaptés à son terrain et à ses enjeux et à en interpréter les résultats. Les outils (partie C) sont présentés sous forme de fiches techniques donnant un accès rapide à l’information nécessaire pour les comprendre et les mettre en œuvre : principe, données nécessaires, protocole de mesure, interprétation, exemple de résultats, valeurs guides, points forts et points faibles... Les outils proposés sont les suivants : analyse géomatique des niveaux d’eau, modèles hydrodynamiques distribués à base physique, modèles hydrothermiques à base physique et dispositifs de mesure de température et d’écoulements d’eau, image thermique infrarouge, géochimie, végétation aquatique, invertébrés souterrains. Ce guide s’adresse avant tout aux gestionnaires de l’eau qui, pour gérer de façon durable leurs ressources en eau, doivent s’intéresser aux interactions nappe/rivière. Les informations et la démarche proposées ont donc pour objectif principal d’aider l’utilisateur à mettre en œuvre et réaliser par lui-même une étude pour caractériser les échanges nappe/rivière ou à rédiger le cahier des charges pour la sous-traiter

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

43siAside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.reservedopenDerosa, Lisa; Routy, Bertrand; Thomas, Andrew Maltez; Iebba, Valerio; Zalcman, Gerard; Friard, Sylvie; Mazieres, Julien; Audigier-Valette, Clarisse; Moro-Sibilot, Denis; Goldwasser, François; Silva, Carolina Alves Costa; Terrisse, Safae; Bonvalet, Melodie; Scherpereel, Arnaud; Pegliasco, Hervé; Richard, Corentin; Ghiringhelli, François; Elkrief, Arielle; Desilets, Antoine; Blanc-Durand, Felix; Cumbo, Fabio; Blanco, Aitor; Boidot, Romain; Chevrier, Sandy; Daillère, Romain; Kroemer, Guido; Alla, Laurie; Pons, Nicolas; Le Chatelier, Emmanuelle; Galleron, Nathalie; Roume, Hugo; Dubuisson, Agathe; Bouchard, Nicole; Messaoudene, Meriem; Drubay, Damien; Deutsch, Eric; Barlesi, Fabrice; Planchard, David; Segata, Nicola; Martinez, Stéphanie; Zitvogel, Laurence; Soria, Jean-Charles; Besse, BenjaminDerosa, Lisa; Routy, Bertrand; Thomas, Andrew Maltez; Iebba, Valerio; Zalcman, Gerard; Friard, Sylvie; Mazieres, Julien; Audigier-Valette, Clarisse; Moro-Sibilot, Denis; Goldwasser, François; Silva, Carolina Alves Costa; Terrisse, Safae; Bonvalet, Melodie; Scherpereel, Arnaud; Pegliasco, Hervé; Richard, Corentin; Ghiringhelli, François; Elkrief, Arielle; Desilets, Antoine; Blanc-Durand, Felix; Cumbo, Fabio; Blanco, Aitor; Boidot, Romain; Chevrier, Sandy; Daillère, Romain; Kroemer, Guido; Alla, Laurie; Pons, Nicolas; Le Chatelier, Emmanuelle; Galleron, Nathalie; Roume, Hugo; Dubuisson, Agathe; Bouchard, Nicole; Messaoudene, Meriem; Drubay, Damien; Deutsch, Eric; Barlesi, Fabrice; Planchard, David; Segata, Nicola; Martinez, Stéphanie; Zitvogel, Laurence; Soria, Jean-Charles; Besse, Benjami

Dossier de presse INRA 2017 : microbiote, la révolution intestinale

Dossier de presse INRAil s'agit d'un type de produit dont les métadonnées ne correspondent pas aux métadonnées attendues dans les autres types de produit : REPORTDossier de presse INRA 2017 : microbiote, la révolution intestinal

Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

International audienceIn recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported(1,2). In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis(3,4). Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa(3,4). These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication

Human gut microbes impact host serum metabolome and insulin sensitivity

MetaHIT Consortium: Almeida M, Antolin M, Artiguenave F, Batto JM, Bertalan M, Blottiere H, Boruel N, Brechot C, Bruls T, Burgdorf K, Casellas F, Cultrone A, de Vos WM, Delorme C, Denariaraz G., Derrien M, Dervyn R, Feng Q, Grarup N, Guarner F, Guedon E, Haimet F, Jamet A, Juncker A, Juste C, Kennedy S, Khaci G, Kleerebezem M, Knoll J, Layec S, Leclerc M, Leonard P, LePaslier D, m'Rini C, Maguin E, Manichanh C, Mende D, Merieux A, Oozer R, Parkhill J, Pelletier E, POns N, QinJ, rasmussen S, Renault P, Rescigno M, Sanchez N, Sicheritz-Ponten T, Tap J, Tims S, Torrejon A, Turner K, van de Guchet M, van hylckama Vlieg JE, Vandemeulebrouck G, Varela E, Veiga P, Weissenbach J, Winogradski Y, Yamada T, Zoetendal EGInsulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders