IRS1 and Insulin resistance: Endotoxin (lypopolisaccharides—LPS) translocation in the systemic circulation due to gut dysbiosis cis one of the main drivers of immunomodulation: once entered into the bloodstream, LPS binds to the CD14/TLR4 complex on the macrophage’s surface and favors M1 macrophage proliferation with subsequent production of TNFα, IL-1β, and IL-6, which contribute to insulin resistance by phosphorylating serine of IRS-1; as a result, insulin signaling is reduced, triggering insulin resistance [71].