Beneficial effects of exercise on gut microbiota functionality and barrier integrity, and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease

• Published in: Disease models & mechanisms 2019-05, Vol.12 (5)
• Main Authors: Carbajo-Pescador, Sara, Porras, David, García-Mediavilla, María Victoria, Martínez-Flórez, Susana, Juarez-Fernández, María, Cuevas, María José, Mauriz, José Luis, González-Gallego, Javier, Nistal, Esther, Sánchez-Campos, Sonia
• Format: Article
• Language: English
• Subjects: Animals; Bile Acids and Salts - metabolism; Body weight gain; Childhood obesity; Diet; Diet, High-Fat; Disease Models, Animal; Enterohepatic Circulation; Exercise; Fatty acids; Fatty Acids - biosynthesis; Fecal metabolome; Feces; Fitness training programs; Gastrointestinal Microbiome; Gene expression; Gut-liver axis; Inflammation - pathology; Insulin resistance; Intestinal microbiota; Intestines - pathology; Lipid Metabolism; Lipids; Liver - injuries; Liver - pathology; Liver diseases; Male; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - complications; Metabolome; Microbiota; Non-alcoholic Fatty Liver Disease - microbiology; Obesity; Obesity - microbiology; Overweight; Oxidative Stress; Pediatrics; Physical Conditioning, Animal; Physical fitness; Principal Component Analysis; Rats, Wistar; Rodents
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.039206

Childhood obesity has reached epidemic levels, representing one of the most serious public health concerns associated with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). There is limited clinical experience concerning pediatric NAFLD patients, and thus the therapeutic options are scarce. The aim of this study was to evaluate the benefits of exercise on gut microbiota composition and functionality balance, and consequent effects on early obesity and NAFLD onset in an model. Juvenile (21-day-old) male Wistar rats fed a control diet or a high-fat diet (HFD) were subjected to a combined aerobic and resistance training protocol. Fecal microbiota was sequenced by an Illumina MiSeq system, and parameters related to metabolic syndrome, fecal metabolome, intestinal barrier integrity, bile acid metabolism and transport, and alteration of the gut-liver axis were measured. Exercise decreased HFD-induced body weight gain, metabolic syndrome and hepatic steatosis, as a result of its lipid metabolism modulatory capacity. Gut microbiota composition and functionality were substantially modified as a consequence of diet, age and exercise intervention. In addition, the training protocol increased , and genera, correlating with a beneficial metabolomic profile, whereas , and showed an opposite pattern. Exercise effectively counteracted HFD-induced microbial imbalance, leading to intestinal barrier preservation, which, in turn, prevented deregulation of the gut-liver axis and improved bile acid homeostasis, determining the clinical outcomes of NAFLD. In conclusion, we provide scientific evidence highlighting the benefits of gut microbiota composition and functionality modulation by physical exercise protocols in the management of early obesity and NAFLD development.