Effects of social stress and hypercaloric diet on depression, chronic pain and associated biological variables: what is the role of the microbiota?

Abstract

Depression and chronic pain are two conditions that present themselves as comorbidities. They share several behavioral characteristics and are associated with neuroplasticity processes, chronic subclinical inflammation and similar metabolic changes. In chronic pathologies, there is an interaction between genetic background and environmental factors or circumstances determining its development. Two very important environmental conditions are stress and diet. Thus, there is a complex interrelationship between environmental factors, such as chronic stress and diet quality, pathological conditions such as depression and chronic pain, and also some shared pathophysiological processes. A phenomenon that has recently gained scientific interest and clinical relevance is intestinal dysbiosis, that is, the condition of imbalance in the intestinal microbiota. Intestinal dysbiosis begins to be discussed in the context of depression and chronic pain, as well as in relation to metabolic and inflammatory processes, in addition to the gut-brain molecular communication. In this scenario, this study aims to investigate the effects of chronic social stress and cafeteria diet on the depressive-like behaviors and response to nociceptive stimuli in animal models addressing shared processes of neuroplasticity, chronic subclinical inflammation and metabolic changes . Special focus will be given to the role of intestinal dysbiosis in this complex interrelationship. Therefore, we will submit male mice to the social subjugation chronic stress model or access to the cafeteria diet, or even to the association of these conditions. Throughout the protocol, we will evaluate the composition of the intestinal microbiota, as well as behavioral, neuroplastic, inflammatory and metabolic changes. In a second step, we will evaluate the hypothesis of the participation of microbiota in the changes of the variables studied in the previous step, through experiments of faecal microbiota transplantation from stressed animals and exposed to cafeteria diet for naïve animals. Finally, in the third stage of the study, we will test whether the transplantation of faecal microbiota from control animals (no stress and standard diet) to animals that underwent stress combined with cafeteria diet can reverse the changes in the studied variables. (AU)