Fig. 3
From: The digestive tract as the origin of systemic inflammation
Direct and indirect interactions between the gut and other organs in systemic inflammation. Luminal components of the small intestine can spread to the circulation via the portal vein (PV) and liver. This includes pro-inflammatory constituents such as lipopolysaccharide (LPS), bacterial DNA, whole bacteria, other bacterial products, and free fatty acids (FFAs). Toxic components of the gut lumen, including FFAs, inflammatory products of phospholipase A2 (PLA 2 ), pro-inflammatory cytokines (e.g., IL-17), and damage-associated molecular substrates such as high mobility group box 1 protein (HMGB1), can reach the pulmonary circulation via mesenteric lymph. Bile acids from the liver, including cholic acid, DCA, and chenodeoxycholic acid, mediate cytotoxic effects on intestinal epithelial cells. STAT3 signaling in Kupffer cells (KCs) of the liver maintains tolerance under homeostatic conditions, whereas KCs produce high levels of pro-inflammatory cytokines in systemic inflammation with toxic effects on the lung parenchyma. Finally, activated serine proteases, elastases, and lipases produced by the pancreas can cause local tissue destruction and activation of immune cells in intestinal tissues, leading to exacerbated systemic inflammatory responses