Gut-liver crosstalk in sepsis-induced liver injury

Abstract

Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.

Intestinal Barrier Dysfunction, Bacterial Translocation and Inflammation: Deathly Triad in Sepsis

“…The second mechanical barrier is the polarized single layer of gut epithelial cells (enterocytes-responsible for the absorption, goblet-specialized in mucus production, enteroendocrine cells-responsible for the secretion of the intestinal hormones, Paneth cells-responsible for expressing the microbicidal proteins and peptides among other properties, and microfold cells (M cells)) besides submucosal capillary endothelial cells [21,28,29], which act as a selectively permeable interface allowing the transmigration of the essential nutrients, water, electrolytes, and immune factors, and preventing the transfer of luminal pathogenic microorganisms, antigens, and toxins to the circulatory system [4,[12][13][14]30]. This feature of selectivity is coordinated by the paracellular pathway regulated by desmosomes, adherens junctions, and tight junctions (TJs), located at the apicolateral membrane junction, lateral membrane, and basolateral membrane, respectively, and the transepithelial pathway, which is maintained mainly by the selective transporters allowing the uptake of the nutrients [13,14,28,31] (for a recent review about mechanobiology of TJs, see reference [32]).…”

“…This response leads to an inflammation out of control and eventually multiple organ dysfunction syndrome (MODS), which is the primary cause of sepsis-related deaths. The propulsive force of the severe consequences of sepsis, such as MODS, is the intestines due to its potential to provoke systemic immune response via the injured intestinal epithelia losing its barrier function, and cannot prevent the pathogens and toxins to confined intraluminally and secreting and releasing the pro-inflammatory cytokines into the circulation [1,[3][4][5][6][7][8][9]. In this chapter, we aimed to cover the fate of the intestinal barrier (IB) and bacterial translocation (BT) during sepsis along with diagnostic methods and potential therapeutic options for IB dysfunction in the light of this information.…”

Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4

“…Acute liver injury (ALI) occurs at any stage of sepsis and is an independent risk factor for sepsis-induced death (Sun et al, 2020). Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection (Singer et al, 2016).…”

International Normalized Ratio to Albumin Ratio (PTAR): An Objective Risk Stratification Tool in Patients with Sepsis

“…According to previous studies, mortality rates of septic patients with hepatic dysfunction or failure range from 54 to 68%, which is higher than the mortality rates of septic patients with lung dysfunction or failure which is commonly observed in sepsis. 3 Therefore, recognizing liver injury and dysfunction in sepsis is of great importance to clinicians and scientists.…”