New insights into lipopolysaccharide inactivation mechanisms in sepsis

The complex pathophysiology of sepsis makes it a syndrome with limited therapeutic options and a high mortality rate. Gram-negative bacteria containing lipopolysaccharides (LPS) in their outer membrane correspond to the most common cause of sepsis. Since the gut is considered an important source of LPS, intestinal damage has been considered a cause and a consequence of sepsis. Although important in the maintenance of the intestinal epithelial cell homeostasis, the microbiota has been considered a source of LPS. Recent studies have started to shed light on how sepsis is triggered by dysbiosis, and an increased inflammatory state of the intestinal epithelial cells, expanding the understanding of the gut-liver axis in sepsis. Here, we review the gut-liver interaction in Gram-negative sepsis, exploring the mechanisms of LPS inactivation, including the recently described contribution of an isoform of the cholesteryl-ester transfer protein (CETPI). Although several key questions remain to be answered when the pathophysiology of sepsis is reviewed, new contributions coming to light exploring the way LPS might be inactivated in vivo, suggest that new applications might soon reach the clinical setting. [Display omitted] •An inflammatory environment promotes disruption of the intestinal barrier and LPS translocation to plasma.•The gut-liver axis contains mechanisms to neutralize gut-derived LPS, limiting its presence in the bloodstream.•While important in the maintenance of intestinal epithelial cell homeostasis, the gut microbiota can be a source of LPS.•High-fat diets enhance intestinal permeability contributing to LPS plasma translocation and low-grade gut inflammation.•CETPI is a novel protein that might lead to the development of new biomarkers and therapeutic options in sepsis.