Local intestinal inflammatory response in stroke. As the first intestinal response to AIS, the enteric barrier is disrupted, thus compromising the ability of the microbiota to defend against intestinal pathogens. The microbiota stimulates release of metabolites, neurotransmitters, indoles, short-chain fatty acids, and bile acids that can reach the brain, thus modulating neurons, microglia, astrocytes, and neurovascular unit function. Vagal afference activate neuroendocrine system to release peptides [peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK)], as well as inflammatory response to enhance pro-inflammatory cytokines release (e.g., interleukin (IL)-21) from cluster of differentiation (CD)-4+ T-cells and IL-17 from γδT-cells. IL-17 acts to recall neutrophils by releasing chemokines. Moreover, T lymphocytes can migrate from the Peyer patches of the small intestine or from the intestinal lamina propria to the brain and/or the leptomeninges. As depicted in the inset, the loss of myeloid differentiation primary response protein (MYD)-88 in epithelial cells results in increased bacterial translocation and altered bacterial microbiota. Moreover, nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors-6 (NLRP6) are involved in the maintenance of a stable intestinal microbial community. Usually, NLR proteins create a multiprotein complex named the inflammasome, activating IL-1β and IL-18 secretion and changes in several immune cell populations. B-cells also play an important role in microbiotic homeostasis through secretion of immunoglobulin A, promoted by TCD4+ on plasma cells. Additionally, dendritic cells are stimulated by T regulatory cells to increase the secretion of IL-10. [PYY, peptide YY; GLP-1, glucagon-like peptide-1; CCK, cholecystokinin; IL, interleukin; CD, cluster of differentiation; MYD, myeloid differentiation primary response protein; NOD, nucleotide binding oligomerization domain-containing protein; NLRP, nucleotide-binding oligomerization domain-containing protein receptor; CRH, corticotropin releasing hormone; ACTH, adrenocorticotropic hormone].