Effect of the dietary supplement PERMEAPROTECT+ TOLERANCE© on gut permeability in a human co-culture epithelial and immune cells model.

Background and objective: The leaky gut syndrome is characterized by an intestinal hyperpermeability observed in multiple chronic disorders. Alterations of the gut barrier are associated with translocation of bacterial components increasing inflammation, oxidative stress and eventually dysfunctions of cellular interactions at the origin pathologies. Therapeutic and/or preventive approaches have to focus on the identification of novel targets to improve gut homeostasis. In this context, this study aims to identify the role of PERMEAPROTECT + TOLERANE©, known as PERMEA, a food complement composed of a combination of factors (including l-Glutamine) known to improve gut physiology. Methods: We tested the effects of PERMEA or l-Glutamine alone (as reference) on gut permeability (FITC dextran method, expression of tight junctions) and its inflammatory/oxidative consequences (cytokines and redox assays, RT-qPCR) in a co-culture of human cells (peripheral blood mononuclear cells and intestinal epithelial cells) challenged with TNFα. Results: PERMEA prevented intestinal hyperpermeability induced by inflammation. This was linked with its antioxidant and immunomodulatory properties showing a better efficacity than l-Glutamine alone on several parameters including permeability, global antioxidant charge and production of cytokines. Conclusion: PERMEA is more efficient to restore intestinal physiology, reinforcing the concept that combination of food constituents could be used to prevent the development of numerous diseases.

Limosilactobacillus reuteri BIO7251 administration improves metabolic phenotype in obese mice fed a high fat diet: an inter-organ crosstalk between gut, adipose tissue and nervous system.

Gut microbiota is implicated in the control of host physiology by releasing bioactive actors that could exert a direct or indirect effect on tissue. A dysfunction of the gut microbiota to tissue axis could participate in the development of pathological states such as obesity and diabetes. The aim of this study was to identify the metabolic effect of Limosilactobacillus reuteri (known as Lactobacillus reuteri) BIO7251 (L. reuteri BIO7251) isolated from Corsican clementine orange. Body weight gain, adiposity, glucose tolerance, glucose absorption and food intake were measured in mice fed a high-fat diet in response to a preventive oral administration of L. reuteri BIO7251. This strain of bacteria exerts a beneficial effect on body weight gain by decreasing the subcutaneous adipose tissue mass. The treatment with L. reuteri BIO7251 decreases glucose absorption and food intake in obese/diabetic mice. L. reuteri BIO7251 could be tested as new probiotic strain that could manage body weight during obesity.

Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release.

Background and objective: Pasteurized Akkermansia muciniphila cells have shown anti-diabetic effects in rodents and human. Although, its primary site of action consists in maintaining the gut barrier function, there are no study exploring if A. muciniphila controls glycemia via a gut to brain axis. Targeting the gut motility represents an alternative pathway to treat hyperglycemia. Here, we tested the impact of pasteurized A. muciniphila on gut motility, gut-brain axis and glucose metabolism. Methods: We used mice fed a 45% high-fat (HFD) treated or not with pasteurized A. muciniphila MucT during 12 weeks. We measured the effects of the treatment on body weight gain, glucose metabolism (insulin, glycemia, glucose tolerance), gut contraction and enteric neurotransmitter release, and hypothalamic nitric oxide (NO) release. Results: We show that pasteurized A. muciniphila exerts positive effects on different metabolic parameters such as body weight, fat mass, insulin, glycemia and glucose tolerance. This could be explained by the ability of pasteurized A. muciniphila supplementation to decrease duodenal contraction and to increase hypothalamic NO release in HFD mice. Conclusion: We demonstrate a novel mode of action of pasteurized A. muciniphila explaining its beneficial impact on the control of glycemia in a preclinical model of type 2 diabetes via gut-brain axis signaling.

Camu-Camu Reduces Obesity and Improves Diabetic Profiles of Obese and Diabetic Mice: A Dose-Ranging Study.

Overweight, obesity, and their comorbidities are currently considered a major public health concern. Today considerable efforts are still needed to develop efficient strategies able to attenuate the burden of these diseases. Nutritional interventions, some with plant extracts, present promising health benefits. In this study, we evaluated the action of Camu-Camu (Myrciaria dubia), an Amazonian fruit rich in polyphenols and vitamin C, on the prevention of obesity and associated disorders in mice and the abundance of Akkermansia muciniphila in both cecum and feces. Methods: We investigated the dose-response effects of Camu-Camu extract (CCE) in the context of high-fat-diet (HFD)-induced obesity. After 5 weeks of supplementation, we demonstrated that the two doses of CCE differently improved glucose and lipid homeostasis. The lowest CCE dose (62.5 mg/kg) preferentially decreased non-HDL cholesterol and free fatty acids (FFA) and increased the abundance of A. muciniphila without affecting liver metabolism, while only the highest dose of CCE (200 mg/kg) prevented excessive body weight gain, fat mass gain, and hepatic steatosis. Both doses decreased fasting hyperglycemia induced by HFD. In conclusion, the use of plant extracts, and particularly CCE, may represent an additional option in the support of weight management strategies and glucose homeostasis alteration by mechanisms likely independent from the modulation of A. muciniphila abundance.

Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice.

OBJECTIVE: The enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes. DESIGN: We measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human. RESULTS: We found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic. CONCLUSIONS: Using a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.