Figure 1.

Redox signaling pathways involved in GIB/BBB integrity and inflammasome activation in MS. Gut dysbiosis, irrespective of its cause, leads to: (1) increased ROS/RNS concentration; (2) dysregulation of the Nrf2/Keap1 protective pathway; (3) decreased expression of Nrf2/ARE transcription factors, which leads to activation of the NFkB pathway, in turn promoting gut inflammation and leading to GIB disruption; (4) GIB disruption increases the permeability to small active compounds released by gut bacteria and makes it easier for bacteria to invade by lowering the local immune defense; (5) active gut microbiota metabolites trigger the BBB disruption and increase ROS/RNS and pro-inflammatory molecule levels through inhibition of Nrf2; and (6) increased ROS levels in the brain induce mitochondrial disfunction and inflammasome activation.