The digestive tract as the origin of systemic inflammation

Table 1 Gut-liver crosstalk in systemic inflammation

Major finding	Study type	Reference
Bacteremia due to bacterial translocation is associated with an increased risk of bacterial peritonitis	Human	[51]
Hepatic encephalopathy is associated with changes in the intestinal microbiota	Human	[52]
Acute liver rejection is associated with changes in intestinal microbiota, loss of gut barrier, and enhanced systemic inflammation	Rodent	[55, 56]
CX3CR1 signaling by intestinal macrophages regulates steatohepatitis	Rodent	[58]
A hepatic vascular and phagocytic network functions as a “secondary firewall” to filter escaped gut commensals	Rodent	[60]
Liver cirrhosis is associated with increased inflammasome activation in ascitic fluid macrophages	Human	[61]
Translocation of bacterial DNA in liver cirrhosis is associated with enhanced systemic inflammatory activity	Human	[62, 63]
Hepatic STAT3 signaling protects against systemic inflammation caused by polymicrobial sepsis	Rodent	[72]
Hepatic gp130-STAT3 signaling induces myeloid-derived suppressor cells that protect against polymicrobial sepsis	Rodent	[73]
Hepatic STAT3 signaling regulates cellular and humoral pulmonary immunity against bacterial infection	Rodent	[74]
The liver enhances and protects against systemic inflammation through Kupffer cell-mediated cytokine production and detoxification by parenchymal cells, respectively	Rodent	[76]
Kupffer cells aggravate lung damage in acute pancreatitis	Rodent	[78, 79]

Summary of key studies that addressed the bidirectional gut–liver crosstalk in the pathogenesis of systemic inflammation. The type of study (animal model or human) is indicated
STAT3 signal transducer and activator of transcription 3

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