Leaky gut barrier leads to systemic inflammation
In healthy patients, the gut epithelia form a barrier, connected by tight junction proteins including claudins, occludins and ZO-1, to prevent molecules in the gut lumen from crossing into the blood. However, in diseases including asthma and obesity, tight junctions can become weak, allowing molecules of endotoxin (LPS) to cross into the circulatory system, which can cause an immune response and inflammation. This can occur through several mechanisms; firstly, LPS can bind to TLR-4, which activates the NF-κB signalling pathway and increases the expression of inflammatory cytokines. Secondly, when LPS binds to TLR-4 it can also lead to a signalling cascade that decreases the expression of tight junction proteins, weakening the gut barrier and allowing more LPS to cross. Finally, LPS can be transported into gut cells by chylomicrons, which usually transport fat to the liver and adipose tissues. LPS is taken up by the chylomicrons, they enter the cell and are packaged by the Golgi apparatus, before exiting the cells and into the circulatory system via vesicles.