Clinical Practice Guidelines for Childbearing Female Candidates for Bariatric Surgery, Pregnancy, and Post-partum Management After Bariatric Surgery

Emerging evidence suggests that bariatric surgery improves pregnancy outcomes of women with obesity by reducing the rates of gestational diabetes, pregnancy-induced hypertension, and macrosomia. However, it is associated with an increased risk of a small-for-gestational-age fetus and prematurity. Based on the work of a multidisciplinary task force, we propose clinical practice recommendations for pregnancy management following bariatric surgery. They are derived from a comprehensive review of the literature, existing guidelines, and expert opinion covering the preferred type of surgery for women of childbearing age, timing between surgery and pregnancy, contraception, systematic nutritional support and management of nutritional deficiencies, screening and management of gestational diabetes, weight gain during pregnancy, gastric banding management, surgical emergencies, obstetrical management, and specific care in the postpartum period and for newborns

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Objective: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with bodyfat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between fecal A. muciniphila abundance, fecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). Design: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilization (WS) diet in overweight and obese adults (N=49, including 41 women). Fecal A. muciniphila abundance, fecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and WS. Results: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio, and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. A. muciniphila was associated with microbial species known to be related to health. Conclusion: A. muciniphila is associated with a healthier metabolic status and better clinicaloutcomes after CR in overweight/obese adults, however the interaction between gut microbiota ecology and A. muciniphila has to be taken into account

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

Combinatorial, additive and dose-dependent drug–microbiome associations

Data availability: The source data for the figures are provided at Zenodo (https://doi.org/10.5281/zenodo.4728981). Raw shotgun sequencing data that support the findings of this study have been deposited at the ENA under accession codes PRJEB41311, PRJEB38742 and PRJEB37249 with public access. Raw spectra for metabolomics have been deposited in the MassIVE database under the accession codes MSV000088043 (UPLC–MS/MS) and MSV000088042 (GC–MS). The metadata on disease groups and drug intake are provided in Supplementary Tables 1–3. The demographic, clinical and phenotype metadata, and processed microbiome and metabolome data for French, German and Danish participants are available at Zenodo (https://doi.org/10.5281/zenodo.4674360).Code availability: The new drug-aware univariate biomarker testing pipeline is available as an R package (metadeconfoundR; Birkner et al., manuscript in preparation) at Github (https://github.com/TillBirkner/metadeconfoundR) and at Zenodo (https://doi.org/10.5281/zenodo.4721078). The latest version (0.1.8) of this package was used to generate the data shown in this publication. The code used for multivariate analysis based on the VpThemAll package is available at Zenodo (https://doi.org/10.5281/zenodo.4719526). The phenotype and drug intake metadata, processed microbiome, and metabolome data and code resources are available for download at Zenodo (https://doi.org/10.5281/zenodo.4674360). The code for reproducing the figures is provided at Zenodo (https://doi.org/10.5281/zenodo.4728981).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 discovery1,2,3,4,5. 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, and 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 agents 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.This work was supported by the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312 (METACARDIS). Part of this work was also supported by the EMBL, by the Metagenopolis grant ANR-11-DPBS-0001, by the H2020 European Research Council (ERC-AdG-669830) (to P.B.), and by grants from the Deutsche Forschungsgemeinschaft (SFB1365 to S.K.F. and L.M.; and SFB1052/3 A1 MS to M.S. (209933838)). Assistance Publique-Hôpitaux de Paris is the promoter of the clinical investigation (MetaCardis). M.-E.D. is supported by the NIHR Imperial Biomedical Research Centre and by grants from the French National Research Agency (ANR-10-LABX-46 (European Genomics Institute for Diabetes)), from the National Center for Precision Diabetic Medicine – PreciDIAB, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001), by the European Union (FEDER), by the Hauts-de-France Regional Council (Agreement 20001891/NP0025517) and by the European Metropolis of Lille (MEL, Agreement 2019_ESR_11) and by Isite ULNE (R-002-20-TALENT-DUMAS), also jointly funded by ANR (ANR-16-IDEX-0004-ULNE), the Hauts-de-France Regional Council (20002845) and by the European Metropolis of Lille (MEL). R.J.A. is a member of the Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Bioscience. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research institution at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation

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 discovery. 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, and 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 agents 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

Grossesse et diabète prégestationnel (étude de 142 femmes suivies dans le service de diabétologie de la Pitié entre 1999 et 2004)

La grossesse chez une femme diabétique est une situation à risque tant sur le plan fœtal que maternel. Nous avons étudié 142 patientes prises en charge consécutivement dans le service de Diabétologie de la Pitié pendant leur grossesse, entre 1999 et 2004, et présentant un diabète prégestationnel : 78 patientes diabétiques de type 1 (55%), et 64 patientes diabétiques de type 2 (45%). Nous avons mis en évidence un taux de malformations, de prématurité et de césariennes respectivement 1.5, 3 et 3 fois plus élevés que dans la population générale, sans augmentation par contre de la mortalité maternelle et périnatale. Le taux de programmation est stable depuis 10 ans : 54% pour les patientes diabétiques de type 1 et 22,2% pour celles de type 2, significativement liés aux caractéristiques sociodémographiques des patientes. Notre travail manque de puissance pour montrer de façon significative un lien entre la programmation et les différents paramètres du pronostic maternel et fœtal. Mais, chez les patientes diabétiques de type 1, la programmation réduit significativement le nombre d'hospitalisations et assure l'obtention d'une meilleure HbA1c tout au long de la grossesse ; une HbA1c préconceptionnelle inférieure ou égale à 7% permet quant à elle de réduire le taux de prématurité, de malformations, et d'hospitalisations. Les taux de macrosomie sont très hétérogènes (de 15 à 28%) selon les définitions employées. L'index pondéral nous paraît être la définition la plus pertinente compte-tenu de son lien avec l'HbA1c des 2ème et 3ème trimestres, et la morbidité néonatale. Un effort particulier est indispensable dans la prise en charge des patientes diabétiques de type 2 : leur prévalence a augmenté de 25% en 10 ans, et il existe un retard au diagnostic (15,6% découvert après la période d'embryogenèse). Nous encourageons le dépistage du diabète chez toutes les femmes ayant des facteurs de risque en âge de procréer, et une adaptation des messages de programmation, également en extra hospitalier, envers une population jusqu'ici peu concernée.PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Contraception dans le contexte de l’obésité

La question de l’influence de l’obésité sur la contraception peut être envisagée sous plusieurs angles : comme facteur de risque d’échec d’une contraception hormonale ; comme facteur de risque cardio-vasculaire, pouvant majorer ce risque lors de l’association à une contraception hormonale. Les modifications métaboliques observées au cours de l’obésité et la masse corporelle plus importante des femmes présentant une obésité peuvent en effet être à l’origine d’une réduction de l’efficacité de la contraception hormonale. Néanmoins, les données, mêmes peu nombreuses, laissent penser que l’efficacité de la plupart des méthodes de contraception n’est a priori pas diminuée chez ces femmes. La chirurgie bariatrique, utilisée pour remédier à l’obésité, constitue une situation complexe, qui impose une contraception dans la première année post-opératoire afin d’éviter toute grossesse. Si la technique chirurgicale induit une malabsorption (comme le bypass), toute contraception administrée par voie orale verra son efficacité fortement diminuée et sera donc déconseillée en raison d’un haut risque d’échec

How Can Maternal Lifestyle Interventions Modify the Effects of Gestational Diabetes in the Neonate and the Offspring? A Systematic Review of Meta-Analyses

International audienceGestational diabetes (GDM) has deleterious effects on the offspring. Maternal obesity and excessive gestational weight gain (GWG), often associated with diabetes, also contribute to these adverse outcomes.OBJECTIVES:To assess the benefit for the offspring of maternal lifestyle interventions, including diets and physical activity, to prevent or to improve GDM and to limit excessive GWG.METHOD:Systematic review of meta-analyses published in English between December 2014 and November 2019.RESULTS:Lifestyle interventions to reduce the risk of GDM reported a decreased risk of 15% to 40%, with a greater effect of exercise compared to diet. Combined lifestyle interventions specifically designed to limit GWG reduced GWG by 1.6 kg in overweight and obese women, and on average by 0.7 to 1 kg in all pregnant women. In these trials, adverse neonatal outcomes were poorly studied. Combined lifestyle interventions in women with GDM significantly reduced fetal growth. Altogether, lifestyle interventions reduced the risk of preterm birth and shoulder dystocia, but individually, diets or exercise alone had no effect on neonatal adverse outcomes.CONCLUSION:Specific maternal, neonatal and offspring benefits of lifestyle interventions during pregnancy to prevent or improve GDM control or to limit GWG still require clarification