Critical Flicker Fusion Frequency: A Marker of Cerebral Arousal During Modified Gravitational Conditions Related to Parabolic Flights

In situ evaluation of human brain performance and arousal remains challenging during operational circumstances, hence the need for a rapid, reliable and reproducible tool. Here we hypothesized that the Critical flicker fusion frequency (CFFF) reflecting/requiring visual integration, visuo-motor skills and decision-taking process might be a powerful, fast and simple tool in modified gravity environments. Therefore 11 male healthy volunteers were assessed for higher cognitive functions with CFFF during parabolic flights. They were assessed at different time points: upon arrival to the base, 30 min after subcutaneous scopolamine administration, before parabolas, during hypergravity and microgravity at break time (between the 16th and the 17th parabola), on the return flight and on the ground after landing. First, a stable, and consistent measurement of CFFF could be obtained within 12 s. Second, under modified gravitational conditions, the perceptual ability of participants is significantly modified. Compared to the baseline, evolution is characterized by a significant increase of CFFF when in microgravity (0g: 106.9 ± 5.5%), and a significant decrease of CFFF while in hypergravity (2g: 94.5 ± 3.8%). Other time-points were not statistically different from the baseline value. Although the underlying mechanism is still debated, we suggest that the CFFF test is a global marker of cerebral arousal as the result of visuo-motor and decision taking testing based on a simple visual stimulus with an uncomplicated set up that could be used under various environmental conditions. The authors express an opinion that it would be advisable to introduce CFFF measurement during spaceflights as it allows individual longitudinal assessment of individual ability even under conditions of incomplete physiological compensation, as shown here during parabolic flights

Impact of metformin and Dysosmobacter welbionis on diet-induced obesity and diabetes: from clinical observation to preclinical intervention.

peer reviewed[en] AIMS/HYPOTHESIS: We aimed to investigate the association between the abundance of Dysosmobacter welbionis, a commensal gut bacterium, and metabolic health in human participants with obesity and diabetes, and the influence of metformin treatment and prebiotic intervention. METHODS: Metabolic variables were assessed and faecal samples were collected from 106 participants in a randomised controlled intervention with a prebiotic stratified by metformin treatment (Food4Gut trial). The abundance of D. welbionis was measured by quantitative PCR and correlated with metabolic markers. The in vitro effect of metformin on D. welbionis growth was evaluated and an in vivo study was performed in mice to investigate the effects of metformin and D. welbionis J115T supplementation, either alone or in combination, on metabolic variables. RESULTS: D. welbionis abundance was unaffected by prebiotic treatment but was significantly higher in metformin-treated participants. Responders to prebiotic treatment had higher baseline D. welbionis levels than non-responders. D. welbionis was negatively correlated with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and fasting blood glucose levels in humans with obesity and type 2 diabetes. In vitro, metformin had no direct effect on D. welbionis growth. In mice, D. welbionis J115T treatment reduced body weight gain and liver weight, and improved glucose tolerance to a better level than metformin, but did not have synergistic effects with metformin. CONCLUSIONS/INTERPRETATION: D. welbionis abundance is influenced by metformin treatment and associated with prebiotic response, liver health and glucose metabolism in humans with obesity and diabetes. This study suggests that D. welbionis may play a role in metabolic health and warrants further investigation. CLINICAL TRIAL: NCT03852069

Microbiota and Metabolite Profiling as Markers of Mood Disorders: A Cross-Sectional Study in Obese Patients

Obesity is associated with an increased risk of several neurological and psychiatric diseases, but few studies report the contribution of biological features in the occurrence of mood disorders in obese patients. The aim of the study is to evaluate the potential links between serum metabolomics and gut microbiome, and mood disturbances in a cohort of obese patients. Psychological, biological characteristics and nutritional habits were evaluated in 94 obese subjects from the Food4Gut study stratified according to their mood score assessed by the Positive and Negative Affect Schedule (PANAS). The fecal gut microbiota and plasma non-targeted metabolomics were analysed. Obese subjects with increased negative mood display elevated levels of Coprococcus as well as decreased levels of Sutterella and Lactobacillus. Serum metabolite profile analysis reveals in these subjects altered levels of several amino acid-derived metabolites, such as an increased level of L-histidine and a decreased in phenylacetylglutamine, linked to altered gut microbiota composition and function rather than to differences in dietary amino acid intake. Regarding clinical profile, we did not observe any differences between both groups. Our results reveal new microbiota-derived metabolites that characterize the alterations of mood in obese subjects, thereby allowing to propose new targets to tackle mood disturbances in this context. Food4gut, clinicaltrial.gov: NCT03852069

Gut microbiome composition is linked to whole grain-induced immunological improvements

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans

La traversée de rue chez le piéton sénior : conception d'un simulateur, étude biomécanique et comportementale

In the framework of population ageing and increased importance attached to walking in urban cities, the aim of this PhD work is to better understand behavioral and biomechanical characteristics of older pedestrian road crossing. We mostly used the experimental method. Some data were collected in laboratory or natural environment, but the main study was performed in an immersive road crossing simulator with projected reality: the Simulator of Road for Pedestrians (SRP). The curb height was adjustable. The device integrated various biomechanical measurement tools such as force plates and 3D-gait analysis systems. The real and the imagined crossing times were compared in a task performed outside the simulator. It reveals that some seniors underestimated their crossing time. The experiment within the simulator confirmed the relevance of the age-related modulation of the crossing time perception, which was indirectly estimated by the feeling of endangerment. Inside the simulator, the road crossing behavior of the elderly participants was safe, requiring longer temporal intervals for deciding to initiate the crossing. In favorable traffic gap conditions, they walked more quickly than the younger participants and their safety margins were larger. The biomechanical approach revealed intergroup differences, some of which inducing potential risks (e.g., plantar flexion) while others (e.g., exploratory rotations) participated in the coping.Dans un contexte de vieillissement démographique et de mutation des modes de déplacements urbains majorant la place du piéton, ce travail de thèse vise à mieux comprendre les caractéristiques comportementales et biomécaniques de la traversée de rue des piétons âgés. La méthodologie est essentiellement expérimentale. Si quelques données ont été recueillies en laboratoire ou en environnement naturel, l'étude principale a été conduite dans un simulateur immersif de réalité projetée, outil dénommé Simulateur de Rues pour Piétons (SRP). La hauteur de trottoir est modulable. Le dispositif intègre différents outils de mesures, tels des plates-formes de force et un système d'analyse gestuelle en trois dimensions. Hors simulateur, la comparaison des temps de traversée réelle et estimée, sur un champ de marche, révèle l'occurrence d'un risque de sous-estimation a priori du temps nécessaire chez certains seniors. L'expérience en simulateur confirme l'importance de la modulation exercée par le vieillissement sur la perception du temps en tant que déterminant des estimations a posteriori des temps de traversées quantifiées via la sensation de mise en danger. En simulateur, les seniors adoptent un comportement sécuritaire, requérant des intervalles temporels plus longs pour décider d'initier une traversée. Dans des conditions de trafic favorables, ils marchent plus rapidement que les jeunes. Leurs marges de sécurité sont plus grandes. L'approche biomécanique, révèle des différences intergroupes, dont certaines sont potentiellement à risque (ex. la flexion plantaire) alors que d’autres (ex. les rotations exploratoires) participent à l’adaptation

Road crossing by the elderly pedestrian : simulator design, biomechanical and behavioral analyses.

Dans un contexte de vieillissement démographique et de mutation des modes de déplacements urbains majorant la place du piéton, ce travail de thèse vise à mieux comprendre les caractéristiques comportementales et biomécaniques de la traversée de rue des piétons âgés. La méthodologie est essentiellement expérimentale. Si quelques données ont été recueillies en laboratoire ou en environnement naturel, l'étude principale a été conduite dans un simulateur immersif de réalité projetée, outil dénommé Simulateur de Rues pour Piétons (SRP). La hauteur de trottoir est modulable. Le dispositif intègre différents outils de mesures, tels des plates-formes de force et un système d'analyse gestuelle en trois dimensions. Hors simulateur, la comparaison des temps de traversée réelle et estimée, sur un champ de marche, révèle l'occurrence d'un risque de sous-estimation a priori du temps nécessaire chez certains seniors. L'expérience en simulateur confirme l'importance de la modulation exercée par le vieillissement sur la perception du temps en tant que déterminant des estimations a posteriori des temps de traversées quantifiées via la sensation de mise en danger. En simulateur, les seniors adoptent un comportement sécuritaire, requérant des intervalles temporels plus longs pour décider d'initier une traversée. Dans des conditions de trafic favorables, ils marchent plus rapidement que les jeunes. Leurs marges de sécurité sont plus grandes. L'approche biomécanique, révèle des différences intergroupes, dont certaines sont potentiellement à risque (ex. la flexion plantaire) alors que d’autres (ex. les rotations exploratoires) participent à l’adaptation.In the framework of population ageing and increased importance attached to walking in urban cities, the aim of this PhD work is to better understand behavioral and biomechanical characteristics of older pedestrian road crossing. We mostly used the experimental method. Some data were collected in laboratory or natural environment, but the main study was performed in an immersive road crossing simulator with projected reality: the Simulator of Road for Pedestrians (SRP). The curb height was adjustable. The device integrated various biomechanical measurement tools such as force plates and 3D-gait analysis systems. The real and the imagined crossing times were compared in a task performed outside the simulator. It reveals that some seniors underestimated their crossing time. The experiment within the simulator confirmed the relevance of the age-related modulation of the crossing time perception, which was indirectly estimated by the feeling of endangerment. Inside the simulator, the road crossing behavior of the elderly participants was safe, requiring longer temporal intervals for deciding to initiate the crossing. In favorable traffic gap conditions, they walked more quickly than the younger participants and their safety margins were larger. The biomechanical approach revealed intergroup differences, some of which inducing potential risks (e.g., plantar flexion) while others (e.g., exploratory rotations) participated in the coping

Modulation of the gut microbiota-adipose tissue-muscle interactions by prebiotics.

The gut microbiota is now widely recognized as an important factor contributing to the regulation of host metabolic functions. Numerous studies describe an imbalance in the gut microbial ecosystem in response to an energy-dense diet that drives the development of metabolic disorders. In this context, the manipulation of the gut microbiota by food components acting as prebiotics appears as a promising strategy. Several studies have already investigated the beneficial potency of prebiotics, mostly inulin-type fructans, on host metabolism and key intestinal functions including gut hormone release. For the last 20 years, several non-digestible compounds present in food have been shown to modulate the gut microbiota and influence host metabolism in essential organs involved in the control of energy homeostasis. To date, numerous reviews summarize the impact of prebiotics on the liver or the brain. Here we propose to describe the mechanisms by which prebiotics, through modulation of the gut microbiota and endocrine functions, modulates the metabolic cross-talk communication between the gut, the adipose tissue and skeletal muscles

Nutrition and Microbiome.

The prevalence of overweight and obesity has reached epidemic proportions globally over the past few decades. The search for new management approaches continues and among them, targeting the gut microbiota can be envisioned. To date, numerous data showed the involvement of the gut microbes in the regulation and control of host metabolism. There are also increasing evidences highlighting the interactions between environmental factors, intrinsic factors, gut microbiota, and metabolic diseases. Diet emerges as the most relevant factor influencing the gut microbiome. Eating habits, as well as short-term consumption of specific diets, alter the gut microbiota composition. Moreover, nutritional disorders are associated with changes of the gut microbiota composition and/or function, as shown in obesity or type 2 diabetic patients versus healthy lean subjects. Targeting the gut microbiota for improving metabolic health appears as a new approach to manage obesity and cardio-metabolic risk. In this review, we have detailed the results of human interventions targeting the gut microbiome by prebiotic supplementation, prebiotics being defined as "substrates that are selectively utilized by the host microorganisms conferring a health benefit." If the potential benefit of this approach is obvious in preclinical models, the efficacy of prebiotics in humans is less reproducible. The inter-individual variability of response to dietary intervention can be dependent on the gut microbiota and we summarized the basal gut microbiota characteristics driving the metabolic response to dieting, prebiotic and dietary fiber intervention in the context of obesity and related metabolic diseases

Metformin: old friend, new ways of action-implication of the gut microbiome?

PURPOSE OF REVIEW: Gut dysbiosis was recently associated with the occurrence of type 2 diabetes (T2D). In addition to this finding, an increasing number of studies performed upon the last 5 years have also shown that metformin treatment leads to changes in gut bacterial composition in diabetic patients. This review focuses on the articles describing the effects of metformin on gut homeostasis (including the gut microbiota) and proposes potential mechanisms involved in those effects. RECENT FINDINGS: Several human and animal studies emphasized that metformin alters the gut microbiota composition by enhancing the growth of some bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and by decreasing the levels of some other ones like Intestinibacter. In-vitro studies also demonstrated a direct action of metformin on the growth of A. muciniphila and Bifidobacterium adolescentis. Moreover, in the intestines, metformin does not only improve the glucose uptake, but it also promotes the short-chain fatty acid (SCFA) production, protects the intestinal barrier and regulates the secretion of gut peptides SUMMARY: It is now clear that gut microbiota participates to the glucose-lowering effects of metformin in the context of diabetes. Further work is now needed to determine the exact mechanisms of action of the drug and to understand by which processes metformin is able to enhance the growth of some bacteria exhibiting beneficial effects for the host