Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Les déterminants de santé globale perçus et exprimés par des enfants et adolescents âgés de 6 à 17 ans : revue systématique des études qualitatives

International audienc

Déterminants de la santé et du cancer: investigation des conceptions des enfants de 6 à 11 ans

International audienceContext :Qualitative data on how children and adolescents view their health and its determinants are relatively few at the international level. This research is therefore part of a comprehensive and open-minded approach to better describe how elementary school children perceive the determinants of health and cancer.Objectives :Our main objective is to map, from a multiphase qualitative protocol, the conceptions and systems of conceptions on the determinants of health and cancers perceived within a 6 to 11 age group.The secondary objective is to analyze our ability to collect these healthy conceptions from children.Methodology :Four different tools were used in four schools for 320 students: (1) “photo expression”, (2) “QC (Questions / Certainties)”, (3) “photo narration” and (4) “focus group”. This open and exploratory method, combining the use of photographs and focus groups, provided data on the experiences, stated practices and knowledge of each student. The mobilization of image mediation methods plays an essential ethical role by ensuring the distance between the theme and the child. The informative value of data from qualitative collection tools coupled with a mixed analysis methodology (qualitative and quantitative) allows us to collect dense and efficient data needed to understand the perception of determinants by elementary school students.Conclusion:This study identifies promising methodological leads thanks to the complementarity of the different phases mobilized. It also provides us with elements of methodological understanding that can contribute to the development of prevention tools as part of the school health education journey.Contexte : Les données qualitatives sur la façon dont les enfants et adolescents considèrent leur santé et ses déterminants sont relativement peu nombreuses au plan international. Cette recherche s’inscrit donc dans une perspective compréhensive et ouverte visant à mieux décrire comment des enfants d’école élémentaire perçoivent les déterminants de la santé et des cancers.Objectifs : Notre objectif prioritaire est de cartographier, à partir d’un protocole qualitatif multiphasé, les conceptions et systèmes de conceptions sur les déterminants de la santé et des cancers perçus au sein d’une tranche d’âge de 6 à 11 ans.L’objectif secondaire est d’analyser notre capacité à recueillir ces conceptions en santé auprès d’enfants. Méthodologie : Quatre outils différents ont été utilisés, dans quatre écoles, auprès de 320 élèves : (1) le photo expression, (2) le QC (Questions/Certitudes), (3) le photo narration et (4) le groupe focal. Cette méthode ouverte et exploratoire, conjuguant l’usage de photographies et de groupes focaux a permis de recueillir des données relatives aux expériences, aux pratiques déclarées et aux connaissances propres à chaque élève. La mobilisation des méthodes de médiation par l’image jouent un rôle éthique indispensable en garantissant la mise à distance entre la thématique abordée et l’enfant. La valeur informative des données issues d’outils de recueil qualitatif couplée à une méthodologie mixte d’analyse (qualitative et quantitative) nous permet un recueil de données denses et efficientes nécessaires à la compréhension de la perception des déterminants par des élèves d’école élémentaire.Conclusion : Cette étude identifie des pistes méthodologiques prometteuses grâce à la complémentarité des différentes phases mobilisées. Elle nous fournit également des éléments de compréhension méthodologique pouvant contribuer au développement d’outils de prévention dans le cadre du parcours éducatif de santé en milieu scolaire

Certitudes et doutes d'enfants d'école primaire sur le cancer

International audienceThe objective of this research is to explore the phenomenon of doubt in children aged 6 to 11 by analyzing the questions and knowledge they formulate about cancer. This will make it possible to identify the recurring questions and the uncertainties expressed in order to adapt the methods of cancer prevention. Our methodology was based on a multiphase collection structured around 3 tools: e.Photoexpression ©, "QC" (questions / knowledge) and photo narration. We are more specifically interested here in the QC tool which involves asking children to write down 3 pieces of knowledge and 3 questions about cancer. 774 productions were collected from 387 children, ie 523 knowledge and 741 questions. We observe a lack of knowledge about health and cancer in the children we meet. The results are varied but remain focused on the symptoms or the consequences and ultimately very little on the causes. Their recurring questions, associated with the instability of the knowledge expressed, are consistent with the developmental characteristics of the child. This study provides elements of understanding on how children perceive cancer. This supply of information can contribute to the development of prevention tools intended for young people to improve their level of knowledge and thus help reduce their uncertainties.L'objectif de cette recherche est d'explorer le phénomène de doute chez des enfants âgés de 6 à 11 ans en analysant les questions et les connaissances qu'ils formulent sur le cancer. Ceci permettra d'identifier les interrogations récurrentes et les incertitudes exprimées pour adapter les modalités de prévention sur le cancer. Notre méthodologie s'est appuyée sur un recueil multiphasé articulé autour de 3 outils : e.Photoexpression©, « QC » (questions/connaissances) et photo narration. Nous nous intéressons plus spécifiquement ici à l'outil QC qui consiste à demander aux enfants d'écrire 3 connaissances et 3 questions à propos du cancer. 774 productions ont été recueillies auprès de 387 enfants soient 523 connaissances et 741 questions. Nous observons un déficit de connaissances sur la santé et le cancer chez les enfants rencontrés. Les résultats sont variés mais restent focalisés sur les symptômes ou les conséquences et finalement très peu sur les causes. Leurs interrogations récurrentes, associées à l'instabilité des connaissances exprimées, sont en cohérence avec les caractéristiques développementales de l'enfant. Cette étude fournit des éléments de compréhension sur la façon dont les enfants perçoivent le cancer. Cet apport d'informations peut contribuer au développement d'outils de prévention à destination des publics jeunes pour améliorer leur niveau de connaissances et ainsi participer à réduire leurs incertitudes

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis

Abstract The regulation of food intake, a sine qua non requirement for survival, thoroughly shapes feeding and energy balance by integrating both homeostatic and hedonic values of food. Unfortunately, the widespread access to palatable food has led to the development of feeding habits that are independent from metabolic needs. Among these, binge eating (BE) is characterized by uncontrolled voracious eating. While reward deficit seems to be a major contributor of BE, the physiological and molecular underpinnings of BE establishment remain elusive. Here, we combined a physiologically relevant BE mouse model with multiscale in vivo integrative approaches to explore the functional connection between the gut-brain axis and the reward and homeostatic brain structures. Our results show that BE elicits compensatory adaptations requiring the gut-to-brain axis which, through the vagus nerve, relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling. Selective inhibition of peripheral CB1 receptors resulted in a vagus-dependent increased hypothalamic activity, modified metabolic efficiency, and dampened activity of mesolimbic dopamine circuit, altogether leading to the suppression of palatable eating. We provide compelling evidence for a yet unappreciated physiological integrative mechanism by which variations of peripheral eCBs control the activity of the vagus nerve, thereby in turn gating the additive responses of both homeostatic and hedonic brain circuits which govern homeostatic and reward-driven feeding. In conclusion, we reveal that vagus-mediated eCBs/CB1R functions represent an interesting and innovative target to modulate energy balance and food-reward disorders

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis

International audienceThe regulation of food intake, a sine qua non requirement for survival, thoroughly shapes feeding and energy balance by integrating both homeostatic and hedonic values of food. Unfortunately, the widespread access to palatable food has led to the development of feeding habits that are independent from metabolic needs. Among these, binge eating (BE) is characterized by uncontrolled voracious eating. While reward deficit seems to be a major contributor of BE, the physiological and molecular underpinnings of BE establishment remain elusive. Here, we combined a physiologically relevant BE mouse model with multiscale in vivo approaches to explore the functional connection between the gut-brain axis and the reward and homeostatic brain structures. Our results show that BE elicits compensatory adaptations requiring the gut-to-brain axis which, through the vagus nerve, relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling. Selective inhibition of peripheral CB1 receptors resulted in a vagus-dependent increased hypothalamic activity, modified metabolic efficiency, and dampened activity of mesolimbic dopamine circuit, altogether leading to the suppression of palatable eating. We provide compelling evidence for a yet unappreciated physiological integrative mechanism by which variations of peripheral eCBs control the activity of the vagus nerve, thereby in turn gating the additive responses of both homeostatic and hedonic brain circuits which govern homeostatic and reward-driven feeding. In conclusion, we reveal that vagus-mediated eCBs/CB1R functions represent an interesting and innovative target to modulate energy balance and counteract food-reward disorders

First characterization of the parasite Haplosporidium costale in France and development of a real‐time PCR assay for its rapid detection in the Pacific oyster, Crassostrea gigas

The Pacific cupped oyster Crassostrea gigas is one of the most “globalized” marine invertebrates and its production is predominant in many parts of the world including Europe. However, it is threatened by mortality events associated with pathogenic microorganisms such as the virus OsHV-1 and the bacteria Vibrio aestuarianus. C. gigas is also a host for protozoan parasites including haplosporidians. In contrast with Haplosporidium nelsoni previously detected in Europe, H. costale was considered exotic although its presence in French oysters was suggested in the 1980s based on ultrastructural examination. Here, a combination of light and transmission electron microscopy, PCR and sequencing allowed characterizing the presence of the parasite in the context of low mortality events which occurred in 2019 in France. Histological observation revealed the presence of uninucleated, plasmodial and spore stages within the connective tissues of some oysters. Ultrastructural features were similar to H. costale ones in particular the presence of axe-shaped haplosporosomes in spore cytoplasms. Three fragments of the genome including partial small subunit rRNA gene, the ITS-1, 5.8S and ITS-2 array and part of the actin gene were successfully sequenced and grouped with H. costale homologous sequences. This is the first time that the presence of H. costale was confirmed in C. gigas in France. Furthermore, a TaqMan real-time PCR assay was developed and validated (DSe = 92.6% (78.2-99.8) and DSp = 95.5% (92.3-98.6)) to enable the rapid and specific detection of the parasite. The application of the PCR assay on archived samples revealed that the parasite has been present in French oyster populations at least since 2008. Considering the little information available on this parasite, the newly developed TaqMan assay will be very helpful to investigate the temporal and geographic distribution and the life cycle of the parasite in France and more generally in C. gigas geographic range

Antibody-Dependent NK Cell Activation Is Associated with Late Kidney Allograft Dysfunction and the Complement-Independent Alloreactive Potential of Donor-Specific Antibodies

International audienceAlthough kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1(+) cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1-year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of immunosuppressive treatments, robust ADCC responsiveness can be maintained in some KTRs. Because it evaluates both the Fab recognition of alloantigens and Fc-driven NK cell activation, the NK-CHAT represents a potentially valuable tool for the non-invasive and individualized evaluation of humoral risk during transplantation

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n\ua0=\ua0888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n\ua0=\ua02,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics

Combinatorial, additive and dose-dependent drug–microbiome associations

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker\ua0discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects,\ua0and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic\ua0agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease