Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study.

AIMS: Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. METHODS AND RESULTS: We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. CONCLUSION: Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.

French National Authority for Health assessment of metabolic surgery for type 2 diabetes remission-A meta-analysis in patients with class I to III obesity.

OBJECTIVE: Randomized controlled trials (RCTs) have demonstrated the superiority of metabolic surgery (MS) over medical therapy (MT) in patients with obesity and type 2 diabetes, leading, to a joint statement in 2016 proposing MS to patients with class I obesity and uncontrolled glycemia. Yet, these RCTs included few patients with class I obesity (body mass index 30-35 kg/m2) and even fewer patients with overweight. Our aim was to provide an updated systematic review (SR) with meta-analysis (MA) of RCTs reporting diabetes remission (DR) after MS in these patients. RESEARCH DESIGN AND METHODS: We included in the SR with MA only RCTs with at least 24-month follow-up found in Medline, Cochrane Library, Embase, and LiSSA between January 2008 and September 2022 comparing DR post-MT versus post-MS. We calculated relative risk (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel random-effects approach to examine differences in DR between patients allocated to MS versus MT. RESULTS: DR was significantly higher in MS versus MT after 36 months' follow-up in patients with obesity (RR = 6.65 [95 %CI 2.24;19.79]; I² = 27 %; 5 trials, 404 patients), but also specifically in patients with class I obesity (RR = 5.27 [1.31;21.23]; I² = 0 %; 4 trials, 80 patients). Furthermore, and in line with previous results, all additional MAs performed in patients with obesity in this work favor MS (specifically Roux-en-Y gastric bypass) over MT at 24, 36 (only) and 60 months of follow-up. CONCLUSIONS: Although the data available in patients with class I obesity and type 2 diabetes remains limited, MA shows higher rates of DR after MS compared with MT after 36 months' follow-up in these patients. Consequently, the French National Authority for Health French (HAS) recommends MS for these patients.

Osteoarthritis in patients with obesity: The bariatric surgery impacts on its evolution.

Obesity is one of the main modifiable risk factors for osteoarthritis (OA). Moreover, obesity is associated with greater pain intensity and functional limitation, but also with a significantly lower responder rate to intra-articular treatments. Consequently, an arthroplasty is indicated earlier and more frequently in patients with obesity. However, pain and functional symptoms improve slightly less after arthroplasty in patients with obesity, who display higher incidence of early and late complications following prosthetic surgery. Bariatric surgery (BS) has increased worldwide and is efficient to induce major and sustainable weight-loss. Importantly, BS significantly reduces pain and functional limitation in patients with symptomatic knee OA. Biomarkers analysis also revealed a decrease in catabolic factors and an increase in anabolic one after BS suggesting a structural protective effect in knee OA. Nevertheless, the impact of BS prior to arthroplasty remains unclear. BS seems to decrease short- and mid-term complications such as infections or thrombosis. However, BS does not appear to modify long-term complications rate, and may even increase it, especially revisions and infections. Although few studies have compared the symptomatic and functional outcomes of joint replacement with or without BS, these are not significantly improved by prior BS. Despite these heterogeneous results, medico-economic studies found that BS prior to arthroplasty was cost-effective. To conclude, BS could significantly reduce the symptoms of OA and potentially slow its progression, but appears more disappointing in preventing long-term complications of arthroplasties and improving their functional results.

Management of Severe Malnutrition Post-bariatric Surgery Using Artificial Nutrition.

BACKGROUND: Bariatric surgery (BS) results in major and sustained weight loss and improves comorbidities in patients with obesity but can also lead to malnutrition, especially through severe malabsorption and/or surgical complications. Little is known about the efficacy of artificial nutrition (AN) in this setting. METHODS: In this case series, we describe data from consecutive severely malnourished patients after BS (resectional and non-resectional), managed by AN at our hospital unit over a 4-year period. RESULTS: Between January 2018 and June 2022, 18 patients (mean ± SD age 42.2 ± 10.4 years, 94% women) required AN following BS complications. At the time of AN initiation, more than half of the patients (53%) had multiple revisional surgeries (up to four). Mean BMI was 49.7 ± 11.3 kg/m2 before BS and 29.6 ± 9.6 kg/m2 when AN was initiated. Most patients (n=16, 90%) received enteral nutrition. AN management resulted in weight regain (+4.7kg ± 8.0, p=0.034), increased serum albumin (+28%, p=0.02), pre-albumin (+88%, p=0.002), and handgrip strength (+38%, p=0.078). No major AN complication nor death was observed. Median total AN duration was 4.5 months [1-12]. During follow-up, the cumulative duration of hospitalization was 33 days [4-88] with a median of 2.5 hospitalizations [1-8] per patient. CONCLUSION: Malnutrition can occur after any BS procedure, and AN when required in this setting appears safe and effective on nutritional parameters. It is important to recognize the potential risk factors for malnutrition, which include excessive weight loss resulting from surgical complications, eating disorders, multiple revisional BS, and pregnancy.

Out-of-Pocket Expenses in Households of People Living with Obesity in France.

BACKGROUND/OBJECTIVES: Overweight and obesity result in a substantial economic burden in both low- and high-income countries. Moreover, this burden is often underestimated because it only partially accounts for unreimbursed out-of-pocket expenses (OOPE) related to obesity. The objective of our study was not only to evaluate OOPE incurred by people with obesity in relation to their disease with respect to direct medical expenditures and direct non-medical expenditures but also the proportion of people living with obesity who have forgone obesity-related healthcare due to the costs of such care. METHODS: An observational descriptive survey was conducted among people with class II/III obesity attending six obesity treatment centers in France. Volunteer adult participants completed a written/phone questionnaire on their related expenditures over the last 6 months for current expenditures and over the last 5 years for occasional ones. The costs were expressed in 2022 EUR. RESULTS: 299 people participated (age: 46 years [SD: 13.9], women: 72%, BMI ≥40 kg/m2: 62% and 48% with comorbidities). 65% had a professional activity. 83% declared that they had OOPE related to obesity representing annually EUR 2027/individual on average (5% of the household revenue), including weight loss and nutritional products, vitamins, meal programs, gym memberships, psychologists, but mainly adapted clothing, additional travel costs, and others. 15% of the respondents had to modify their professional activity due to obesity and 15% forwent some medical care in the last 12 months. CONCLUSIONS: OOPE is a significant part of the economic burden of obesity. Despite some limitations due to the specificities of the participants and because some costs may be more related to social activities affected by obesity than to healthcare, it seems important to consider these expenditures in cost estimates for obesity.

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.

Revisional Roux-en-Y Gastric Bypass After Sleeve Gastrectomy for Gastro-esophageal Reflux Disease and or Insufficient Weight-Loss: a Comparative Study.

INTRODUCTION: Sleeve gastrectomy (SG) is a popular surgical weight-loss procedure, but there are increasing reports of revisional Roux-Y-gastric-bypass (R-RYGB) to manage weight-loss failure (WLF) or proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) after SG, with little data available in these settings. METHODS: This retrospective study included all consecutive patients undergoing R-RYGB for WLF or RGERD after SG in two bariatric care centers from 2012 to 2018. RESULTS: Of 720 patients, 46 (3.6%) underwent R-RYGB (RGERD, n = 25; 54.4%; WLF, n = 21; 45.6%) within 44.8 ± 27.5 months post-SG. SG had enabled 27% ± 11.6 total weight loss (TWL) in the RGERD group vs. 7.2% ± 12.5% TWL in the WLF group (p < 0.001). At R-RYGB, WLF-group patients had a higher BMI (47.8 ± 8.4 vs. 34.7 ± 6.1 kg/m2; p < 0.001) and a higher number of comorbidities (2.4 ± 1.5 vs 1.5 ± 1.2; p < 0.02) compared to RGERD-group patients, while severe morbidity (Clavien-Dindo ≥ IIIb) was not significantly different between groups (6.5% vs 2.1%, p = 0.6). %TWL was still higher in the RGERD group at 12 months post-R-RYGB (35.6% ± 10.4 vs. 23.8% ± 9.2; p < 0.01) but not after 24 months post-R-RYGB. R-RYGB corrected reflux symptoms in 32 (94%) patients and reduced PPI use in 29 (97%) patients (p < 0.001), with no significant between-group difference. A history of adjustable gastric banding (AGB) (N = 8;17.4%) prior to SG was associated with a similar prevalence of GERD at R-RYGB and a lower %TWL (AGB:13.1 ± 10.2 vs. No AGB:31.6 ± 8.5; p < 0.05) at 3 years post-R-RYGB. CONCLUSION: R-RYGB following SG provides remission of reflux symptoms in 94% of patients and extra weight loss in patients with WLF, except in patients with a history of AGB prior to SG.

Associations of aortic stiffness and intra-aortic flow parameters with epicardial adipose tissue in patients with type-2 diabetes.

Background: It has been shown that increased aortic stiffness is related to type-2 diabetes (T2D) which is considered as a risk factor for cardiovascular disease. Among other risk factors is epicardial adipose tissue (EAT) which is increased in T2D and is a relevant biomarker of metabolic severity and adverse outcome. Purpose: To assess aortic flow parameters in T2D patients as compared to healthy individuals and to evaluate their associations with EAT accumulation as an index of cardiometabolic severity in T2D patients. Materials and methods: Thirty-six T2D patients as well as 29 healthy controls matched by age and sex were included in this study. Participants had cardiac and aortic MRI exams at 1.5 T. Imaging sequences included cine SSFP for left ventricle (LV) function and EAT assessment and aortic cine and phase-contrast imaging for strain and flow parameters quantification. Results: In this study, we found LV phenotype to be characterized by concentric remodeling with decreased stroke volume index despite global LV mass within a normal range. EAT was increased in T2D patients compared to controls (p<0.0001). Moreover, EAT, a biomarker of metabolic severity, was negatively correlated to ascending aortic (AA) distensibility (p=0.048) and positively to the normalized backward flow volume (p=0.001). These relationships remained significant after further adjustment for age, sex and central mean blood pressure. In a multivariate model, presence/absence of T2D and AA normalized backward flow (BF) to forward flow (FF) volumes ratio are both significant and independent correlates of EAT. Conclusion: In our study, aortic stiffness as depicted by an increased backward flow volume and decreased distensibility seems to be related to EAT volume in T2D patients. This observation should be confirmed in the future on a larger population while considering additional biomarkers specific to inflammation and using a longitudinal prospective study design.

Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality.

BACKGROUND: Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure. OBJECTIVES: The authors aimed to explore whether ImP is associated with heart failure and mortality. METHODS: ImP serum measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates. RESULTS: ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01). CONCLUSIONS: The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.

Precision Bariatric/Metabolic Medicine and Surgery.

Indications and techniques of bariatric surgery (BS) have constantly evolved in recent decades and now face new challenges [...].

Follow-Up, Safety, and Satisfaction with Tele-bariatric Follow-Up Implemented During the COVID-19 French Lockdown: a 2-Year Follow-Up Study.

BACKGROUND: The COVID-19 pandemic was initially responsible for a global restricted access to healthcare resources including the follow-up of at-risk populations such as bariatric patients. We substituted face-to-face bariatric follow-up outpatient clinics (FTFC) with teleclinics (TC) during the lockdown. MATERIAL AND METHODS: We retrospectively reviewed data collected on all patients scheduled for TC during the French lockdown period (March 15 to May 15, 2020) (N = 87). Our aims were to present the patients' outcomes at one and 2 years post-TC implementation and describe patient/practitioner satisfaction. RESULTS: Seven (8%) patients required FTFC, and 80 (92%) underwent TC (study population) for preoperative bariatric assessment (N = 3) and postoperative follow-up (N = 77) after 23.6 ± 29 months following surgery. TC was performed with video and audio (N = 46; 57.5%) or audio alone when video was impossible (N = 34; 42.5%). Sixteen (20%) patients presented at least one complication identified at the first TC and were managed accordingly. There were no readmissions at 30/90 days post-TC. At 1-year after the first TC, overall follow-up rate was 94.9% (TC: 73% vs FTFC: 27%). Patients surveyed on the main advantages of TC over FTFC (N = 46) cited: saving time (97.8%) at a mean 3.9 ± 6.4 h saved per TC, work-advantages (94.3%), and comparable relevance of TC (84.8%). At 2 years post-TC implementation, follow-up rate was 93.5% and satisfaction rate was 80%, with 33% of patients preferring to return to FTFC. CONCLUSIONS: TC is a satisfactory substitute for FTFC, enabling continued bariatric follow-up during and beyond the pandemic setting without compromising patient safety. However, the modest satisfaction outcomes at 2 years highlight a need to discuss follow-up preferences in order to achieve optimal outcomes.

Impaired Function of Solute Carrier Family 19 Leads to Low Folate Levels and Lipid Droplet Accumulation in Hepatocytes.

Low serum folate levels are inversely related to metabolic associated fatty liver disease (MAFLD). The role of the folate transporter gene (SLC19A1) was assessed to clarify its involvement in lipid accumulation during the onset of MAFLD in humans and in liver cells by genomic, transcriptomic, and metabolomic techniques. Genotypes of 3 SNPs in a case-control cohort were initially correlated to clinical and serum MAFLD markers. Subsequently, the expression of 84 key genes in response to the loss of SLC19A1 was evaluated with the aid of an RT2 profiler-array. After shRNA-silencing of SLC19A1 in THLE2 cells, folate and lipid levels were measured by ELISA and staining techniques, respectively. In addition, up to 482 amino acids and lipid metabolites were semi-quantified in SLC19A1-knockdown (KD) cells through ultra-high-performance liquid chromatography coupled with mass spectrometry. SNPs, rs1051266 and rs3788200, were significantly associated with the development of fatty liver for the single-marker allelic test. The minor alleles of these SNPs were associated with a 0.6/-1.67-fold decreased risk of developing MAFLD. When SLC19A1 was KD in THLE2 cells, intracellular folate content was four times lower than in wild-type cells. The lack of functional SLC19A1 provoked significant changes in the regulation of genes associated with lipid droplet accumulation within the cell and the onset of NAFLD. Metabolomic analyses showed a highly altered profile, where most of the species that accumulated in SLC19A1-KD-cells belong to the chemical groups of triacylglycerols, diacylglycerols, polyunsaturated fatty acids, and long chain, highly unsaturated cholesterol esters. In conclusion, the lack of SLC19A1 gene expression in hepatocytes affects the regulation of key genes for normal liver function, reduces intracellular folate levels, and impairs lipid metabolism, which entails lipid droplet accumulation in hepatocytes.

From Dyspnea to Skin Grafting: The Difficulties of Managing a Patient with Extreme Obesity.

While the prevalence of severe obesity is increasing worldwide, caregivers are often challenged with the management of patients with extreme weight. A 30-year-old woman (weight 245 kg, body mass index 85 kg/m2) presented with dyspnea, for which investigations led to suspect pulmonary embolism. The patient's weight made it impossible to perform adapted imaging; thus, an empirical anticoagulant treatment was initiated. A hematoma of the thigh occurred as a consequence of a transient antivitamin K overdose, leading to a 15-cm necrotic wound worsened by a state of malnutrition. Multidisciplinary and comprehensive care was performed including wound trimming, antibiotics, skin grafting, treatment of malnutrition, and psychological support, but with marked difficulties due to the lack of adapted medical equipment and facilities as well as appropriate medical guidelines. Overall, 7 months of hospitalization including 4 months of physiotherapy and rehabilitation were needed before the patient could return home. This case highlights how difficult managing patients with extreme obesity can be and points to the importance for healthcare systems to adapt to the specific needs of these patients and to design specific guidelines for treatment dosage and malnutrition prevention and treatment in this setting.

Effect of exercise training after bariatric surgery: A 5-year follow-up study of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: We previously showed in a 6-month randomized controlled trial that resistance training and protein supplementation after bariatric surgery (Roux-en-Y gastric bypass, RYGB) improved muscle strength without significant effect on weight loss and body composition changes. We performed a 5-year follow-up study in these subjects with the aim 1) to assess the long-term effect of this exercise training intervention and 2) to analyze associations between habitual physical activity (PA) and weight regain at 5 years. METHODS: Fifty-four out of 76 initial participants (follow-up rate of 71%) completed the 5-year follow-up examination (controls, n = 17; protein supplementation, n = 22; protein supplementation and resistance training, n = 15). We measured body weight and composition (DXA), lower-limb strength (leg-press one-repetition maximum) and habitual PA (Actigraph accelerometers and self-report). Weight regain at 5 years was considered low when <10% of 12-month weight loss. RESULTS: Mean (SD) time elapse since RYGB was 5.7 (0.9) y. At 5 years, weight loss was 32.8 (10.1) kg, with a mean weight regain of 5.4 (SD 5.9) kg compared with the 12-month assessment. Moderate-to-vigorous PA (MVPA) assessed by accelerometry did not change significantly compared with pre-surgery values (+5.2 [SD 21.7] min/d, P = 0.059), and only 4 (8.2%) patients reported participation in resistance training. Muscle strength decreased over time (overall mean [SD]: -49.9 [53.5] kg, respectively, P<0.001), with no statistically significant difference between exercise training intervention groups. An interquartile increase in MVPA levels was positively associated with lower weight regain (OR [95% CI]: 3.27 [1.41;9.86]). CONCLUSIONS: Early postoperative participation in a resistance training protocol after bariatric surgery was not associated with improved muscle strength after 5 years of follow-up; however, increasing physical activity of at least moderate intensity may promote weight maintenance after surgery. PA may therefore play an important role in the long-term management of patients with obesity after undergoing bariatric procedure.

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.

Effect of COVID-19 Lockdowns on Physical Activity, Eating Behavior, Body Weight and Psychological Outcomes in a Post-Bariatric Cohort.

PURPOSE: Little is known about the consequences of COVID-19 lockdowns on physical activity (PA), eating behavior, and mental health in post-bariatric surgery (BS) patients. We aimed to analyze the relations between changes in PA during COVID-19 lockdowns and changes in body weight and a comprehensive set of lifestyle and psychological outcomes in patients who have undergone BS. MATERIAL AND METHODS: In April-May 2020 (lockdown#1), we performed an online survey in a cohort of 937 adults who underwent BS and were followed-up at our university medical center for at least one year. We assessed changes in PA, eating behavior, body weight, fatigue, and depression (PHQ-9). In November-December 2020 (lockdown#2), we recorded body weight in 280 patients who had reported decreased PA during lockdown #1. RESULTS: During lockdown #1 (N = 420 patients included, 44% response rate), decreased PA was reported by 67% patients. Compared to those who reported increased or unchanged PA, patients with decreased PA were more likely to report a ≥ 5% weight gain (OR (95% CI): 3.15 (1.46-7.65), increased fatigue (2.08 (1.36-3.23)), a worsening of eating behavior (2.29 (1.47-3.58)), and moderate-to-severe depressive symptoms (4.74 (2.14-11.76)). During lockdown #2 (N = 225 patients, 80% response rate), significant weight gain since before lockdown #1 was reported (+ 2.8 (95% CI: 1.7-3.8) kg, p < 0.001), with 36% patients reporting a ≥ 5% weight gain. CONCLUSIONS: PA may counteract detrimental effects of COVID-19 lockdown on post-BS weight trajectories and mental health outcomes. Follow-up measures are needed in this setting to assess the long-term impact of lockdown.

[new recommandation for medical and surgical care of obesity]. / Chirurgie bariatrique : vers de nouvelles recommandations.

BARIATRIC SURGERY: TOWARDS NEW RECOMMANDATIONS The french NICE has produced a document describing the current limits to the optimal care of obesity, in particular concerning bariatric surgery. This document also states the perspectives and work that needs to be undergone to improve obesity care. Since october 2020, a working group appointed by the French NICE is writing the clinical recommandations for obesity care in 2nd and 3rd care referral, addressing both the medical and surgical care of obesity. This work has known some delay mainly due to the several waves of COVID-19.

CHIRURGIE BARIATRIQUE: VERS DE NOUVELLES RECOMMANDATIONS La Haute Autorité de santé (HAS) s'est autosaisie pour produire une note de cadrage « Parcours obésité ¼ rappelant les limites actuelles de la prise en charge de cette maladie et établir une liste de propositions et de travaux à conduire pour l'améliorer. L'un d'entre eux est la production de recommandations de « prise en charge de l'obésité de l'adulte dans les 2e et 3e recours de soin ¼, travail en cours depuis octobre 2020, mais retardé par la pandémie de Covid-19. Ces recommandations concerneront la prise en charge non seulement médicale mais aussi chirurgicale de l'obésité.

Intermittent Hypoxia Rewires the Liver Transcriptome and Fires up Fatty Acids Usage for Mitochondrial Respiration.

Sleep Apnea Syndrome (SAS) is one of the most common chronic diseases, affecting nearly one billion people worldwide. The repetitive occurrence of abnormal respiratory events generates cyclical desaturation-reoxygenation sequences known as intermittent hypoxia (IH). Among SAS metabolic sequelae, it has been established by experimental and clinical studies that SAS is an independent risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). The principal goal of this study was to decrypt the molecular mechanisms at the onset of IH-mediated liver injury. To address this question, we used a unique mouse model of SAS exposed to IH, employed unbiased high-throughput transcriptomics and computed network analysis. This led us to examine hepatic mitochondrial ultrastructure and function using electron microscopy, high-resolution respirometry and flux analysis in isolated mitochondria. Transcriptomics and network analysis revealed that IH reprograms Nuclear Respiratory Factor- (NRF-) dependent gene expression and showed that mitochondria play a central role. We thus demonstrated that IH boosts the oxidative capacity from fatty acids of liver mitochondria. Lastly, the unbalance between oxidative stress and antioxidant defense is tied to an increase in hepatic ROS production and DNA damage during IH. We provide a comprehensive analysis of liver metabolism during IH and reveal the key role of the mitochondria at the origin of development of liver disease. These findings contribute to the understanding of the mechanisms underlying NAFLD development and progression during SAS and provide a rationale for novel therapeutic targets and biomarker discovery.

Microbiome and metabolome features of the cardiometabolic disease spectrum.

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.