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International audience; A multispecies Lactobacillus- and Bifidobacterium-containing probiotic mixture significantly reduced the adverse metabolic and inflammatory effects of a 14-week high-fat diet in wild-type C57/BL6J mice gavaged 5 days a week with the probiotic mixture or vehicle. Recent evidence indicates that the gut microbiome may play a decisive role in the onset of obesity and associated chronic metabolic diseases, such as type 2 diabetes, by modulating nutrient absorption and factors conducive to development of a persistent low-grade inflammatory state. By modifying the gut microbiome, probiotics might constitute an effective dietary strategy for managing these metabolic disorders. The tested probiotic mixture significantly attenuated the increase in body weight, serum glucose concentration and insulin resistance induced by the high-fat diet. Furthermore, it significantly reduced the up-regulation of expression of several genes encoding pro-inflammatory adipokines and leukotriene pathway enzymes (CCL-2, IL-6 and leukotriene C4 synthase in adipose tissue, leukotriene C4 synthase and leukotriene A4 hydrolase in the gut). It also significantly counteracted the down-regulation of adipose tissue gene expression related to the anti-inflammatory adipokine adiponectin in mice fed the high-fat diet. These results suggest that the mechanism underlying the beneficial metabolic effects of the probiotic mixture might involve inhibition of gut and adipose tissue inflammation.

International audience; A role of the gut microbiota in psychiatric disorders is supported by a growing body of literature. The effects of a probiotic mixture of four bacterial strains were studied in two models of anxiety and depression, naturally stress-sensitive Fischer rats and Long Evans rats subjected to maternal deprivation. Rats chronically received either the probiotic mixture (1.10(9) CFU/day) or the vehicle. Anxiety- and depressive-like behaviors were evaluated in several tests. Brain monoamine levels and gut RNA expression of tight junction proteins (Tjp) and inflammatory markers were quantified. The gut microbiota was analyzed in feces by 16S rRNA gene sequencing. Untargeted metabolite analysis reflecting primary metabolism was performed in the cecal content and in serum. Fischer rats treated with the probiotic mixture manifested a decrease in anxiety-like behaviors, in the immobility time in the forced swimming test, as well as in levels of dopamine and its major metabolites, and those of serotonin metabolites in the hippocampus and striatum. In maternally deprived Long Evans rats treated with the probiotic mixture, the number of entries into the central area in the open-field test was increased, reflecting an anxiolytic effect. The probiotic mixture increased Tjp1 and decreased Ifn gamma mRNA levels in the ileum of maternally deprived rats. In both models, probiotic supplementation changed the proportions of several Operational Taxonomic Units (OTU) in the gut microbiota, and the levels of certain cecal and serum metabolites were correlated with behavioral changes. Chronic administration of the tested probiotic mixture can therefore beneficially affect anxiety- and depressive-like behaviors in rats, possibly owing to changes in the levels of certain metabolites, such as 21-deoxycortisol, and changes in brain monoamines.

Epilepsy is a neurological condition that affects 1% of the world population. Conventional treatments of epilepsy use drugs targeting neuronal excitability, inhibitory or excitatory transmission. Yet, one third of patients presents an intractable form of epilepsy and fails to respond to pharmacological anti-epileptic strategies. The ketogenic diet is a well-established non-pharmacological treatment that has been proven to be effective in reducing seizure frequency in the pharmaco-resistant patients. This dietary solution is however extremely restrictive and can be associated with complications caused by the high [fat]:[carbohydrate + protein] ratio. Recent advances suggest that the traditional 4:1 ratio of the ketogenic diet is not a requisite for its therapeutic effect. We show here that combining nutritional strategies targeting specific amino-acids, carbohydrates and fatty acids with a low [fat]:[proteins + carbohydrates] ratio also reduces excitatory drive and protects against seizures to the same extent as the ketogenic diet. Similarly, the morphological and molecular correlates of temporal lobe seizures were reduced in animals fed with the combined diet. These results provide evidence that low-fat dietary strategies more palatable than the ketogenic diet could be useful in epilepsy.

International audience; Rhodiola rosea L. (R. rosea) is an adaptogenic plant increasing body resistance to stress. Its efficacy has been evidenced mainly in chronic stress models, data concerning its effect in acute stress and underlying mechanisms being scarce. The objective was to investigate the effect of repeated doses of a R. rosea hydroethanolic root extract (HRE) on hypothalamic pituitary adrenal response in a murine model of acute mild stress and also the mechanisms involved. Stress response was measured in Balb/c mice having received by gavage HRE (5 g/kg) or vehicle daily for 2 weeks before being submitted to an acute mild stress protocol (open‐field test then elevated plus maze). Corticosterone was measured in plasma from mandibular vein blood drawn before and 30, 60, and 90 min after initiation of the stress protocol. Mice were sacrificed at 90 min, and the hippocampus, prefrontal cortex, and amygdala were excised for high‐frequency RT‐PCR gene expression analysis. At 30 min after acute mild stress induction, corticosterone level in mice having received the HRE was lower than in control mice and comparable to that in nonstressed mice in the HRE group. HRE administration induced brain structure‐dependent changes in expression of several stress‐responsive genes implicated in neuronal structure, HPA axis activation, and circadian rhythm. In the acute mild stress model used, R. rosea HRE decreased corticosterone level and increased expression of stress‐responsive genes, especially in the hippocampus and prefrontal cortex. These findings suggest that R. rosea HRE could be of value for modulating reactivity to acute mild stress.

International audience; SCOPE: Targeting gut microbiota dysbiosis by prebiotics is effective, though side-effects such as abdominal bloating and flatulence may arise following high prebiotic consumption over weeks. Our aim was therefore to optimize the current protocol for prebiotic use. METHODS AND RESULTS: To examine the prebiotic properties of plant extracts, we conducted two independent studies in ob/ob mice, over two weeks. In the first study, we evaluated Porphyra umbilicalis and Melissa officinalis L. extracts; in the second study, we assessed a high- vs. low-dose of an Emblica officinalis Gaertn extract. These plant extracts affected gut microbiota, caecum metabolome and induced a significant lower plasma triacylglycerols (TG) following the treatment with P. umbilicalis and significant higher plasma free fatty acids (FFA) following treatment with the low-dose of E. officinalis Gaertn. Glucose- and insulin-tolerance were not affected but white adipose tissue and liver gene expression were modified. In the first study, IL-6 hepatic gene expression was significantly (adjusted P = 0.0015) and positively (r = 0.80) correlated with the bacterial order Clostridiales in all mice. CONCLUSION: Our data show that a 2-week treatment with plant extracts affects the dysbiotic gut microbiota and changes both caecum metabolome and markers of lipid metabolism in ob/ob mice.

International audience; Increasing evidence suggests that polyphenols have a significant potential in the prevention and treatment of risk factors associated with metabolic syndrome. The objective of this study was to assess the metabolic outcomes of two polyphenol-containing extracts from cinnamon bark (CBE) and grape pomace (GPE) on C57BL/6J mice fed a high-fat diet (HFD) for 8 weeks. Both CBE and GPE were able to decrease fat mass gain and adipose tissue inflammation in mice fed a HFD without reducing food intake. This was associated with reduced liver steatosis and lower plasma non-esterified fatty acids levels. We also observed a beneficial effect on glucose homeostasis as evidenced by an improved glucose tolerance and a lower insulin resistance index. These ameliorations of the overall metabolic profile were associated to a significant impact on the microbial composition, which was more profound for the GPE than for the CBE. At the genus level, Peptococcus were decreased in the CBE group. In the GPE treated group, several key genera that have been previously found to be linked with HFD, metabolic effects and gut barrier integrity were affected: we observed a decrease of Desulfovibrio, Lactococcus, whereas Allobaculum and Roseburia were increased. In addition, the expression of several antimicrobial peptides and tight junction proteins was increased in response to both CBE and GPE supplementation, indicating an improvement of the gut barrier function. Collectively, these data suggest that CBE and GPE can ameliorate the overall metabolic profile of mice on a high-fat diet, partly by acting on the gut microbiota.

International audience; Lutein is recovered at high concentration in the human macula lutea. Recent studies suggest that this micronutrient might be implicated in prevention of age-related macular degeneration. Objective. To identify genes which affect blood and retina lutein concentrations among candidate genes (intestinal sterol transporters and carotenoid oxygenases). Design. A comparative plus an observational study. Participants. Twenty-nine healthy subjects for the comparative study and 622 subjects for the observational study. Intervention and methods. All the participants were genotyped for single nucleotide polymorphisms (SNPs) in the candidate genes. Fasting plasma lutein concentrations were measured in all the participants and after 6 months' supplementation, with either a lutein-rich supplement or a placebo, in the 29 subjects who participated in the comparative study. Macular pigment optical density (MPOD), which is a measure of macula concentration of lutein, was measured before and after the dietary intervention in the 29 subjects. Associations between SNPs and plasma lutein and MPOD were assessed by partial least square (PLS) regression followed by univariate analysis. Observed associations between SNPs and plasma lutein were verified by haplotype-based association analysis in the cohort of 622 subjects. Main outcome measures. Plasma lutein levels and MPOD. Results. Six SNPs in four genes (ABCG8, BCMO1, CD36, and NPC1L1) explained 25% and 38% of the plasma and MPOD variance, respectively. Subjects with TT at the BCMO1 rs7501331 locus had lower (P < 0.05) plasma lutein than CT subjects. Subjects with CC at the CD36 rs13230419 locus had lower (P < 0.05) plasma lutein than subjects who carried a T allele. The association between CD36 and plasma lutein was confirmed in the cohort of 622 subjects. Subjects with TT at the BCMO1 rs7501331 locus had a higher (P < 0.05) MPOD, and subjects with GG at rs1761667 CD36 locus had a higher (P < 0.05) MPOD than those with an A allele. Conclusions. These results suggest that BCMO1 and CD36 are implicated in plasma and retina concentrations of lutein and that genetic variants in these genes can modulate blood and retina concentrations of lutein.

Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. Methods In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Results Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Conclusions Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. Trial Registration ClinicalTrials.gov NCT01530685