ABSTRACT
Diabetes is rapidly emerging as one of the biggest health concerns worldwide, with profound implications for disability, mortality, and costs. This suddenly escalating rate of diabetes correlates with global industrialization and the production of plastics, pesticides, synthetic fertilizers, electronic waste, and food additives that release endocrine-disrupting chemicals (EDCs) into the environment and the food chain. Emerging evidence indicates an association between exposure of EDCs and diabetes. In humans, these chemicals are also metabolized by the gut microbiota and thereby their toxicodynamics are altered. In this review we highlight studies that focus on the role of gut microbiota in EDC-induced hyperglycemia and dysregulated glucose homeostasis. We also discuss the translational implications of understanding EDC-microbiota interactions for the diagnosis and treatment of diabetes.
Subject(s)
Diabetes Mellitus/epidemiology , Endocrine Disruptors/toxicity , Gastrointestinal Microbiome/physiology , Animals , Diabetes Mellitus/etiology , Diabetes Mellitus/microbiology , Endocrine Disruptors/metabolism , Environmental Pollutants/toxicity , Epidemics , Humans , Inactivation, Metabolic/physiology , IncidenceABSTRACT
The gastrointestinal nerves are crucial in the sensing of nutrients and hormones and its translation in terms of control of food intake. Major macronutrients like glucose and proteins are sensed by the extrinsic nerves located around the portal vein walls, which signal to the brain and account for the satiety phenomenon they promote. Glucose is sensed in the portal vein by neurons expressing the glucose receptor SGLT3, which activates the main regions of the brain involved in the control of food intake. Proteins indirectly act on food intake by inducing intestinal gluconeogenesis and its sensing by the portal glucose sensor. The mechanism involves a prior antagonism by peptides of the µ-opioid receptors present in the portal vein nervous system and a reflex arc with the brain inducing intestinal gluconeogenesis. In a comparable manner, short chain fatty acids produced from soluble fibers act via intestinal gluconeogenesis to exert anti-obesity and anti-diabetic effects. In the case of propionate, the mechanism involves a prior activation of the free fatty acid receptor FFAR3 present in the portal nerves and a reflex arc initiating intestinal gluconeogenesis.
