The liver-gut-axis: initiator and responder to sepsis

The 'gut-liver axis' is thought to play an important role in pathogenesis of sepsis. Despite a wealth of experimental data to support the concept of reciprocal crosstalk between gut and liver through bacterial translocation and shaping of the microbiome by liver-derived molecules, for example bile acids, clinical data, and in particular diagnostic and therapeutic options, are limited.

Assessment of organ failure in the current definition of sepsis is operationalized by means of the Sequential Organ Failure Assessment (SOFA) score, including exclusively bilirubin to reflect the complex functions of the liver but ignoring the gut. However, our understanding of the intestinal microbiome and how it is affected by critical illness has clearly improved. Microbiota maintain gut-barrier function and modulate the innate and adaptive immune system. The best-defined intervention affecting the gut microbiome, that is selective decontamination of the digestive tract (SDD) is clinically studied regarding prevention of nosocomial lung infection and antibiotic resistance patterns, although its impact on liver function has not been systematically evaluated in critical illness.

Characterization of liver function beyond bilirubin and the microbiome can be achieved with contemporary sequencing and metabolomic techniques. Such studies are essential to understand how gut-liver crosstalk and 'dysbiosis' affect susceptibility to and outcome of sepsis.