Nathalie Vionnet

Background/Objectives: Despite recognized physiological limitations, serum prealbumin continues to be measured during nutritional follow-up after bariatric surgery, and low concentrations may be interpreted as indicating inadequate lean-mass preservation. We aimed to evaluate the clinical utility of serum prealbumin for identifying disproportionate DXA-derived lean mass loss during the first three years after Roux-en-Y gastric bypass (RYGB) and to examine its association with DXA-derived lean-mass measurements at long-term follow-up. Methods: In a longitudinal cohort of 178 adults, serum prealbumin and dual-energy X-ray absorptiometry (DXA)-derived body composition were assessed preoperatively, at 6 months, 1 year, and 3 years after surgery. Disproportionate lean mass loss was defined as lean mass accounting for >25% of total body weight lost. A complementary cross-sectional analysis examined associations between prealbumin and body composition in 310 participants assessed at a median of 8.8 years after RYGB. Results: Prealbumin decreased from an estimated 0.260 g/L preoperatively to 0.203 g/L at 6 months and partially recovered thereafter, while absolute lean mass continued to decline through 3 years. Prealbumin showed poor discrimination of disproportionate lean mass loss, with AUCs of 0.36, 0.28, and 0.48 at 6 months, 1 year, and 3 years, respectively, although estimates were imprecise because of the small number of participants meeting the criterion. The <0.20 g/L prealbumin threshold showed low sensitivity of 12–27%. Lower prealbumin concentrations were not significantly associated with the percentage of preoperative lean mass lost at any time point. In the long-term analysis, prealbumin was not meaningfully associated with DXA-derived lean mass measures after adjustment for sex, age, and time since surgery. Conclusions: Serum prealbumin showed limited discriminatory performance for identifying disproportionate DXA-derived lean mass loss during the first three years after RYGB, although estimates were imprecise because of the small number of events. In the long-term cross-sectional cohort, associations with DXA-derived lean-mass measurements were weak. These findings do not support the use of serum prealbumin as a surrogate marker of DXA-derived lean mass preservation after RYGB.

Despite major progress in understanding the impact of the triplicated chromosome 21 on the brain and behaviour in Down syndrome, our knowledge of the underlying neurobiology in humans is still limited. We sought to address some of the pertinent questions about the drivers of brain structure differences and their associations with cognitive function in Down syndrome. To this aim, in a pilot magnetic resonance imaging (MRI) study, we monitored brain anatomy in individuals with Down syndrome receiving pulsatile gonadotropin-releasing hormone (GnRH) therapy over 6 months in comparison with typically developed age- and sex-matched healthy controls. We analysed cross-sectional (Down syndrome/healthy controls n = 11/27; Down syndrome—2 females/9 males, age 26.7 ± 5.0 years old; healthy controls—8 females/19 males, age 24.1 ± 2.5 years old) and longitudinal (Down syndrome/healthy controls n = 8/13; Down syndrome—1 female/7 males, age 26.4 ± 5.3 years old; healthy controls—4 females/9 males, 24.7 ± 2.2 years old) relaxometry and diffusion-weighted MRI data alongside standard cognitive assessment. The statistical tests looked for cross-sectional baseline differences and for differential changes over time between Down syndrome and healthy controls. The post hoc analysis confined to the Down syndrome group, tested for potential time-dependent interactions between individuals’ overall cognitive performance and associated brain anatomy changes. The brain MRI statistical analyses covered both grey and white matter regions across the whole brain allowing for investigation of regional volume, macromolecular/myelin and iron content, additionally to diffusion tensor and neurite orientation and dispersion density characterization across major white matter tracts. The cross-sectional analysis showed reduced frontal, temporal and cerebellar volumes in Down syndrome with only the cerebellar differences remaining significant after adjustment for the presence of microcephaly (Pfamily-wise-corrected < 0.05). The volume reductions were paralleled by decreased cortical and subcortical macromolecular/myelin content confined to the cortical motor system, thalamus and basal ganglia (Pfamily-wise-corrected < 0.05). All major white matter tracts showed a ubiquitous mean diffusivity and intracellular volume fraction reduction contrasted with no differences in magnetization transfer saturation metrics (Pfamily-wise-corrected < 0.05). Compared with healthy controls over the same period, Down syndrome individuals under GnRH therapy showed cognitive improvement (Montreal Cognitive Assessment from 11.4 ± 5.5 to 15.1 ± 5.6; P < 0.01) on the background of stability of the observed differential neuroanatomical patterns. Despite the lack of adequate Down syndrome control group, we interpret the obtained cross-sectional and longitudinal findings in young adults as evidence for predominant neurodevelopmental neuronal loss due to dysfunctional neurogenesis without signs for short-term myelin loss.

Objective: This study investigated the effectiveness of liraglutide 3.0 mg daily in combination with a standardized multidisciplinary intervention on body weight and body composition changes in a real‐life setting.Methods: A prospective, observational cohort study design was used. Adult patients with BMI > 35 kg/m², or BMI > 28 kg/m² with greater than or equal to one metabolic comorbidity, were included (n = 54, 65% women). Liraglutide treatment was covered by Swiss health insurance. Clinical and biological data were collected at baseline, 4 months, and 10 months. Body composition was assessed by dual‐energy x‐ray absorptiometry at baseline and 10 months.Results: At 10 months, mean (SD) percentage weight loss (WL%) was −12.4% (5.5%) or −14.1 (6.6) kg. WL% was ≥5% in 87% of patients at 4 months and in 96% at 10 months. WL% was higher in women (−9.5% [3.1%] vs. men −7.2% [2.5%], p = 0.02) at 4 months and persisted at 10 months (−13.7% [5.2%] vs. −9.6% [5.1%], p = 0.006). WL% was associated with baseline percentage fat mass but not with age or BMI. Body composition showed a decrease in fat mass, visceral adipose tissue, and absolute lean mass.Conclusions: In a real‐world setting, liraglutide 3.0 mg led to beneficial changes in WL and body composition, with a greater impact in women.

The identification of molecular biomarkers that can be used to quantitatively link dietary intake to phenotypic traits in humans is a key theme in modern nutritional research. Although dairy products (with and without fermentation) represent a major food group, the identification of markers of their intake lags behind that of other food groups. Here, we report the results from an analysis of the metabolites in postprandial serum and urine samples from a randomized crossover study with 14 healthy men who ingested acidified milk, yogurt, and a non-dairy meal. Our study confirms the potential of lactose and its metabolites as markers of lactose-containing dairy foods and the dependence of their combined profiles on the fermentation status of the consumed products. Furthermore, indole-3-lactic acid and 3-phenyllactic acid are two products of fermentation whose postprandial behaviour strongly discriminates yogurt from milk intake. Our study also provides evidence of the ability of milk fermentation to increase the acute delivery of free amino acids to humans. Notably, 3,5-dimethyloctan-2-one also proves to be a specific marker for milk and yogurt consumption, as well as for cheese consumption (previously published data). These molecules deserve future characterisation in human interventional and observational studies.

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction—gonadotropin-releasing hormone (GnRH)—and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS.

Objective: Bariatric surgery (BS) induces loss of body fat mass (FM) with an inexorable loss of lean mass (LM). Menopause leads to deleterious changes in body composition (BC) related to estrogen deficiency including LM loss and increase in total and visceral adipose tissue (VAT). This study aims to describe the long-term weight evolution of post-menopausal women after Roux-en-Y gastric bypass (RYGB) and to compare the BC between BS patients vs post-menopausal non-operated women. Design: Cross-sectional study of 60 post-menopausal women who underwent RYGB ≥2 years prior to the study with nested case–control design. Methods: Post-menopausal BS women were matched for age and BMI with controls. Both groups underwent DXA scan, lipids and glucose metabolism markers assessment. Results: Median follow-up was 7.5 (2–18) years. Percentage of total weight loss (TWL%) was 28.5 ± 10%. After RYGB, LM percentage of body weight (LM%) was positively associated with TWL% and negatively associated with nadir weight. Forty-one post-BS women were age- and BMI-matched with controls. Post-BS patients showed higher LM% (57.7% (±8%) vs 52.5% (±5%), P = 0.001), reduced FM% (39.4% (±8.4%) vs 45.9% (±5.4%), P < 0.01) and lower VAT (750.6 g (±496) vs 1295.3 g (±688), P < 0.01) with no difference in absolute LM compared to controls. While post-BS women showed a better lipid profile compared to controls, no difference was found in glucose markers. Conclusions: Post-menopausal women after RYGB have a lower FM and VAT, preserved LM and a better lipid profile compared to controls. Weight loss after RYGB seems to have a persistent positive impact on metabolic health.

The use of biomarkers of food intake (BFIs) in blood and urine has shown great promise for assessing dietary intake and complementing traditional dietary assessment tools whose use is prone to misreporting. Untargeted LC-MS metabolomics was applied to identify candidate BFIs for assessing the intake of milk and cheese and to explore the metabolic response to the ingestion of these foods. A randomized controlled crossover study was conducted in healthy adults [5 women, 6 men; age: 23.6 ± 5.0 y; BMI (kg/m²): 22.1 ± 1.7]. After a single isocaloric intake of milk (600 mL), cheese (100 g), or soy-based drink (600 mL), serum and urine samples were collected postprandially up to 6 h and after fasting after 24 h. Untargeted metabolomics was conducted using LC-MS. Discriminant metabolites were selected in serum by multivariate statistical analysis, and their mass distribution and postprandial kinetics were compared. Serum metabolites discriminant for cheese intake had a significantly lower mass distribution than metabolites characterizing milk intake (P = 4.1 × 10⁻⁴). Candidate BFIs for milk or cheese included saccharides, a hydroxy acid, amino acids, amino acid derivatives, and dipeptides. Two serum oligosaccharides, blood group H disaccharide (BGH) and Lewis A trisaccharide (LeA), specifically reflected milk intake but with high interindividual variability. The 2 oligosaccharides showed related but opposing trends: subjects showing an increase in either oligosaccharide did not show any increase in the other oligosaccharide. This result was confirmed in urine. New candidate BFIs for milk or cheese could be identified in healthy adults, most of which were related to protein metabolism. The increase in serum of LeA and BGH after cow-milk intake in adults calls for further investigations considering the beneficial health effects on newborns of such oligosaccharides in maternal milk. The trial is registered at clinicaltrials.gov as NCT02705560.

Trimethylamine-N-oxide (TMAO) can be produced by the gut microbiota from dietary substrates and is associated with cardiovascular disease. While dairy products contain TMAO precursors, the effect of fermented dairy on TMAO metabolism remains unclear. We used plasma and urine samples collected for two randomised cross-over studies to evaluate the effects of fermented dairy consumption on TMAO metabolism. In Study 1, thirteen healthy young men tested a yogurt and an acidified milk during postprandial tests and a two-week daily intervention. In Study 2, ten healthy adults tested milk and cheese during postprandial tests. TMAO and five related metabolites were measured in plasma and urine by LC-MS/MS and NMR. Faecal microbiota composition was assessed in Study 1 (16S rRNA metagenomics sequencing). Fermented milk products were associated with lower postprandial TMAO responses than non-fermented milks in urine (Study 1, p = 0.01; Study 2, p = 0.02) and in plasma, comparing yogurt and acidified milk (Study 1, p = 0.04). Daily consumption of dairy products did not differentially affect fasting TMAO metabolites. Significant correlations were observed between microbiota taxa and circulating or urinary TMAO concentrations. Fermentation of dairy products appear, at least transiently, to affect associations between dairy products and circulating TMAO levels.