What is the role of swainsonine in inducing systemic inflammation in livestock and mice?

Swainsonine is an indolizidine alkaloid produced by the endophytic fungi Alternaria oxytropis in locoweed. It is known to cause various toxic reactions in livestock, including apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading to liver inflammation and neurological disorders. However, the specific mechanisms by which swainsonine induces systemic inflammation, particularly its effects on intestinal permeability, lipopolysaccharide (LPS) levels, and oxidative stress, were previously unclear.

From: "Increased intestinal permeability and lipopolysaccharide contribute to swainsonine-induced systemic inflammation", Ecotoxicology and Environmental Safety, Volume 284, 1 October 2024, 116912

Swainsonine increases intestinal permeability by down-regulating colonic goblet cells and Akkermansia muciniphila, and up-regulating intestinal permeability indicator proteins such as Ptprh. This leads to increased LPS biosynthesis and higher levels of free-form LPS in the blood, which in turn induces high levels of pro-inflammatory cytokines and oxidative stress, causing systemic inflammation.