An altered intestinal barrier leads to immune changes in the gut and the CNS. (1) Multiple sclerosis-associated microbiota and immune derangements lead to an altered barrier and increased permeability. (2) Microbiota diversity is reduced, as is production of SCFA’s, and some bacteria translocate to the lamina propria. (3) LPS produced by bacteria cause low-grade inflammation and endotoxaemia, and loss of SCFA signalling alters lymphocyte phenotypes. (4) LPS, microbial-associated molecular patterns (MAMPs) and reduced SCFAs alter the blood–brain barrier. (5) LPS and activated lymphocytes reach the CNS, where in absence of normal SCFA concentrations, microglia and astrocyte neuroimmune responses are affected. A = astrocytes; BBB = blood–brain barrier; M = microglia; TLR = Toll-like receptors.