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Erica Yeo Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada

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Patricia L Brubaker Department of Physiology, University of Toronto, Toronto, ON, Canada
Department of Medicine, University of Toronto, Toronto, ON, Canada

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Deborah M Sloboda Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
Department of Obstetrics, Gynecology and Pediatrics, McMaster University, Hamilton, ON, Canada

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It is now well established that, beyond its role in nutrient processing and absorption, the intestine and its accompanying gut microbiome constitute a major site of immunological and endocrine regulation that mediates whole-body metabolism. Despite the growing field of host-microbe research, few studies explore what mechanisms govern this relationship in the context of pregnancy. During pregnancy, significant maternal metabolic adaptations are made to accommodate the additional energy demands of the developing fetus and to prevent adverse pregnancy outcomes. Recent data suggest that the maternal gut microbiota may play a role in these adaptations, but changes to maternal gut physiology and the underlying intestinal mechanisms remain unclear. In this review, we discuss selective aspects of intestinal physiology including the role of the incretin hormone, glucagon-like peptide 1 (GLP-1), and the role of the maternal gut microbiome in the maternal metabolic adaptations to pregnancy. Specifically, we discuss how bacterial components and metabolites could mediate the effects of the microbiota on host physiology, including nutrient absorption and GLP-1 secretion and action, and whether these mechanisms may change maternal insulin sensitivity and secretion during pregnancy. Finally, we discuss how these pathways could be altered in disease states during pregnancy including maternal obesity and diabetes.

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Nicole G Barra Department of Biochemistry and Biomedical Sciences, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Fernando F Anhê Department of Biochemistry and Biomedical Sciences, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Joseph F Cavallari Department of Biochemistry and Biomedical Sciences, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Anita M Singh Department of Biochemistry and Biomedical Sciences, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Darryl Y Chan Department of Biochemistry and Biomedical Sciences, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Jonathan D Schertzer Department of Biochemistry and Biomedical Sciences, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Micronutrients influence hormone action and host metabolism. Dietary minerals, trace elements, and vitamins can alter blood glucose and cellular glucose metabolism, and several micronutrients are associated with the risk and progression of type 2 diabetes. Dietary components, microbes, and host immune, endocrine, and metabolic responses all interact in the intestine. There has been a focus on macronutrients modifying the host-microbe relationship in metabolic disease. Micronutrients are positioned to alter host-microbe symbiosis that participates in host endocrine control of glucose metabolism. Minerals and trace elements can alter the composition of the intestinal microbiota, gut barrier function, compartmentalized metabolic inflammation, cellular glucose transport, and endocrine control of glucose metabolism, including insulin and thyroid hormones. Dietary vitamins also influence the composition of the intestinal microbiota and vitamins can be biotransformed by gut microbes. Host-microbe regulation of vitamins can alter immunity, lipid and glucose metabolism, and cell fate and function of pancreatic beta cells. Causal effects of micronutrients in host-microbe metabolism are still emerging, and the mechanisms linking dietary excess or deficiency of specific micronutrients to changes in gut microbes directly linked to metabolic disease risk are not yet clear. Dietary fiber, fat, protein, and carbohydrates are key dietary factors that impact how microbes participate in host glucose metabolism. It is possible that micronutrient and microbiota-derived factors also participate in host-microbe responses that tip the balance in the endocrine control of host glucose metabolism. Dietary micronutrients should be considered, tested, and controlled in pre-clinical and clinical studies investigating host-microbe factors in metabolic diseases.

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Julie Rodriguez Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium

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Nathalie M Delzenne Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium

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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.

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Fabio Arturo Iannotti Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Campania, Italy

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Vincenzo Di Marzo Director, Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition (JIRU-MicroMeNu) between the Consiglio Nazionale delle Ricerche (CNR, Institute of Biomolecular Chemistry) and Université Laval, Naples, Campania, Italy
Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Department of Medicine, Faculty of Medicine and School of Nutrition, Faculty of Agricultural and Food Sciences, CRIUCPQ, INAF and Centre NUTRISS, Université Laval, Québec City, Canada

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Two complex systems are emerging as being deeply involved in the control of energy metabolism. The intestinal microbiota, with its warehouse of genes, proteins and small molecules, that is, the gut microbiome; and the endocannabinoid system, with its recent extension to a more complex signalling apparatus including more than 100 lipid mediators and 50 proteins, that is, the endocannabinoidome. Both systems can become perturbed following bad dietary habits and during obesity, thus contributing to exacerbating this latter condition and its consequences in both peripheral organs and the brain. Here, we discuss some of the multifaceted aspects of the regulation and dysregulation of the gut microbiome and endocannabinoidome in energy metabolism and metabolic disorders, with special emphasis on the emerging functional interactions between the two systems. The potential exploitation of this new knowledge for the development of new pharmacological and nutritional approaches against obesity and its consequences is also briefly touched upon.

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Marion Régnier UCLouvain, Université Catholique de Louvain, WELBIO – Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium

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Matthias Van Hul UCLouvain, Université Catholique de Louvain, WELBIO – Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium

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Claude Knauf Université Paul Sabatier, Toulouse III, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan, Place du Docteur Baylac, Toulouse Cedex 3, France
European Associated Laboratory (EAL) ‘NeuroMicrobiota’, Brussels/Toulouse, Belgium

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Patrice D Cani UCLouvain, Université Catholique de Louvain, WELBIO – Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium
European Associated Laboratory (EAL) ‘NeuroMicrobiota’, Brussels/Toulouse, Belgium

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Overweight and obesity are associated with several cardiometabolic risk factors, including insulin resistance, type 2 diabetes, low-grade inflammation and liver diseases. The gut microbiota is a potential contributing factor regulating energy balance. However, although the scientific community acknowledges that the gut microbiota composition and its activity (e.g. production of metabolites and immune-related compounds) are different between healthy subjects and subjects with overweight/obesity, the causality remains insufficiently demonstrated. The development of low-grade inflammation and related metabolic disorders has been connected with metabolic endotoxaemia and increased gut permeability. However, the mechanisms acting on the regulation of the gut barrier and eventually cardiometabolic disorders are not fully elucidated. In this review, we debate several characteristics of the gut microbiota, gut barrier function and metabolic outcomes. We examine the role of specific dietary compounds or nutrients (e.g. prebiotics, probiotics, polyphenols, sweeteners, and a fructose-rich diet) as well as different metabolites produced by the microbiota in host metabolism, and we discuss how they control several endocrine functions and eventually have either beneficial or deleterious effects on host health.

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