O circuito neural mediado pelo nervo vago regula o perfil proteômico do intestino ao longo do dia

Abstract

Circadian rhythms are fluctuations in physiology and behavior around 24 hours allowing the organisms to predict the environmental changes and to anticipate its responses to better adapt. Circadian rhythm disruption is associated to many gastrointestinal and metabolic disorders such as colitis, irritable bowel syndrome, obesity, and diabetes. Previously, it was shown that food, intestinal microbiota, and metabolites are determinants to the gastrointestinal circadian rhythm synchronization. However, the regulatory mechanism of intestinal biological rhythms is not fully elucidated. Then, we hypothesized that the vagus nerve temporarily organizes the gut physiology. To test it, we used mass spectrometry coupled to liquid chromatography and analyzed the proteome and phosphoproteome rhythms in the ileum, on vagotomized (VNX) or Sham operated mice. We identified that 4,2% of the proteome and 0,47% of the phosphoproteome oscillated through the day, as measured by the JTK cycle test, according to activity and feeding cycles. The identified proteins and phosphoproteins are associated to classical intestinal functions, such as digestion/absorption, metabolism, and epithelial barrier. Surprisingly, the gut-brain axis interruption by vagotomy abolished the protein rhythms. Curiously, in the absence of vagus nerve, some proteins related to immune functions acquired cyclic behavior. These results showed that the gut-brain axis regulates the proteins expression and phosphorylation rhythms related to basic intestinal function. Furthermore, many proteins rhythms were unknown until this moment. Therefore, this work expanded the knowledge about intestinal biological rhythms and will allow the future hypothesis formulation and investigation. Keywords: Intestine. Vagus nerve. Biological rhythms.