Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

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

Un rhizome khmer à la frontière khméro-thaïlandaise : une étude sur les travailleurs illégaux de Rong Klua et de Poipet

Between the town of Poipet and the Rong Klua market, at the border of Thailand and Cambodia, we oberved the movements of illegal populations or those living at the fringes of the society. We realize a sketche of a «geographical» map which allows us to locate and classify the multiple activities in a protean market. In order to know how many persons live in this market, permanently or not, legally or not, we observed various border locations and illegal passages to better understand the relationships and the differences, locally accepted, between legal and illegal workers. Thus, we find out from where these inhabitants came from and why did they come. It seems fundamental to analyze their own reconstitution of a history based on a resilience, a history which became their history, even if it had emerged from poverty and on debris of another history as much significant than misery, because the Khmer Rouge camps where built here. Economic and social relations are re-interpreted within a framework of mental cartography based on myths and rituals, specifically khmer which regains force here. This cartography, build upon a teared apart social network, from a ritual territory, helped by the use of khmer language, allow the Cambodian workers to carry on a symbolic struggle which they daily conduct in order to resist to the Thai domination

Deux combats pour une même idéologie. L’aide humanitaire, un vecteur de la mondialisation ?

1- Un nouveau débat ? Le débat sur l’aide humanitaire est aussi ancien que la volonté d’aider les autres. Il ne s’agit pas ici de reprendre ce débat mais de l’éclairer à travers l’analyse des situations thaïlandaise (le tsunami) et birmane (le cyclone). Notre présence et notre travail sur les lieux de ces drames nous donnent une responsabilité morale et scientifique, celle de partager nos expériences, d’analyser les faits en chercheurs et d’ouvrir un débat. Les justifications de la non-interv..

L’Asie du Sud-Est 2009 : les évènements majeurs de l’année

Chaque année l'Institut de recherche sur l'Asie du Sud-Est contemporaine (Irasec), basé à Bangkok, analyse les principaux événements politiques, économiques, sociaux, environnementaux ou religieux survenus dans l'ensemble du sous-continent asiatique. Plus de dix après la crise qui ébranla les économies asiatiques, l'Asie du Sud-Est est de nouveau confrontée à de graves difficultés qui mettent à mal ses modèles de développement économique et politique. S'agit-il seulement d'une crise de croissance d'une région prise dans la tourmente de l'économie mondiale ou bien est-ce que cette nouvelle dépression qui affecte l'ensemble des pays de la zone a des racines plus profondes ? Etablissant une rétrospective des événements majeurs de l'année 2008 ce livre aide à mieux comprendre les principaux enjeux de l'année 2009 dans une région en perpétuelle évolution et dont les soubresauts peuvent avoir des conséquences jusqu'en Europe. Grâce au travail tout au long de l'année d'une quinzaine de chercheurs et d'experts européens et asiatiques, Asie du Sud-Est 2009 tente de démêler l'éphémère des grandes tendances historiques et offre un décryptage pertinent et contemporain d'une actualité asiatique dense et multiforme. Outre une analyse passionante, cet ouvrage propose de nombreux outils pratiques tels qu'une chronologie détaillée de l'année, les adresses des différents centres de recherche francophones et européens travaillant sur l'Asie du Sud-Est, une bibliographie rassemblant les ouvrages publiés l'année dernière ou encore une liste des centres de documentation et des formations relatives à l'Asie du Sud-Est ainsi que les adresses de librairies spécialisées

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

Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology (Nature Communications, (2020), 11, 1, (5881), 10.1038/s41467-020-19589-w)

The original version of this Article contained an error in the spelling of the author Judith Aron-Wisnewsky, which was incorrectly given as Judith Aron-Wisneswky. This has now been corrected in both the PDF and HTML versions of the Article.</p

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