Effects of microbiota transplantation and the role of the vagus nerve in gut–brain axis in animals subjected to chronic mild stress

Currently, there is a growing emphasis on the study of intestinal signaling as an influencer in the pathophysiology of neuropsychiatric diseases, and the gut–brain axis is recognized as a communication route through endocrine, immune, and neural pathways (vagus nerve). Studies have shown that diets that modify the microbiota can reduce stress-related behavior and hypothalamic–pituitary–adrenal axis activation. Investigators have used fecal microbiota transplantation (FMT) approaches to demonstrate that stress-related microbiota composition plays a causal role in behavioral changes. We hypothesized that FMT may present immunomodulatory, biochemical, endocrine, cognitive, and behavioral benefits in stress situations and that these changes can be mediated via the vagus nerve. Animals were subjected to a chronic mild stress (CMS) protocol. In one experiment, animals were divided into five groups: control, control + FMT, control + FMT + CMS, CMS + saline, and CMS + FMT. The animals received FMT, and behavioral tests were performed; cytokine and carbonyl levels were measured. In a second experiment, animals were submitted to vagotomy and divided into two groups: CMS + FMT and CMS + vagotomy + FMT. Animals submitted to the CMS protocol or that received FMT from stressed animals showed behavioral changes and changes in neuroactive substances (increased IL-6 and TNF-α levels and carbonyl proteins). The FMT of healthy donors improved the analyzed parameters. In addition, vagotomy influenced beneficial FMT results, confirmed by behavioral testing and protein carbonyl in the hippocampus. Manipulation of the microbiota reversed the behavioral and biochemical changes induced by the CMS protocol, and the vagus nerve influenced the gut–brain axis response.