Targeting the Microbiota-Gut-Brain Axis for obesity-induced chronic pain

Abstract

Trabajo presentado en la 13th International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health, celebrado en Praga (República Checa), del 17 al 20 de junio de 2019[Introduction] Obesity is a global epidemic and is associated with increased risk for mortality and several medical morbidities that create a substantial burden on both the aƿicted patients and society. Chronic pain is more frequent and severe among overweight patients and given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying pain development under these particular conditions. Multiple studies have now revealed that the microbiota-gut-brain axis plays a critical role in health and disease. In agreement, modulation of the gut microbiota via probiotic treatment is postulated to be an effective adjunctive therapy for metabolic disorders. In contrast, the role of prebiotics is less investigated. Prebiotic Ƽbres like short-chain fructo-oligosaccharides (FOS) are known to selectively modulate the composition of the intestinal microbiota and specially to stimulate proliferation of the lactobacilli and biƼdobacteria in the gut. [Methods] A model of overweight-induced exposure chronic pain was used in this study. Mice (40 C57Bl6/J male) were randomly assigned to the different diets for an entire period of 8 weeks: hypercaloric high-fat diet (5.21 kcal/g) and control diet (3.87 kcal/g). We tested whether the prebiotic FOS, which increases intrinsic enteric microbiota, affected obesity-induced chronic pain development. Mice were exposed to by exposing the animals to drinking water containing or not FOS during the entire experimental period. The development of allodynia and hyperalgesia were evaluated by using the von Frey and the plantar tests, respectively. Plasma leptin, adiponectin and insulin were measured. Cecum microbiota composition was determined. [Results] High fat diet induced overweight and the development of chronic pain in mice, revealed in the von Frey test. The administration of FOS attenuated body weight and epididymal fat gain and revealed reduced obesity-induced pain development. The prebiotic increased the weight of he cecum and had a positive effect on metabolic hormones such as leptin, insulin and adiponectin. Microbiota composition was also affected by diet and by FOS administration. High-fat diet reduced microbiota diversity and the presence of Roseburia was associated with reduced pain response. [Discussion] These data show that FOS produced a positive impact on obesity-induced pain development in mice. Collectively, our results suggest that prebiotics can ameliorate the overall metabolic proƼle of mice exposed to high-fat diet, partly by acting on the gut microbiota. Future studies in animal models of disease and in humans are now warranted. These Ƽndings strengthen the role of gut microbiota supplementation as prebiotic-based strategies for metabolic related brain-gut axis disorders opening new avenues in the Ƽeld of neurogastroenterology and nutritional neuroscience