Revisiting the gut-liver axis: gut lymphatic system in liver cirrhosis and portal hypertension

Abstract

The lymphatic vascular system runs parallel to the blood vascular system, comprising a network of lymphatic vessels and secondary lymphoid organs. The intestinal lymphatic capillaries (lacteals) and the associated collecting vessels in the mesentery form the gut lymphatic system. The gut lymphatic vasculature comprises the longest-studied lymphatic vessel bed and plays a significant role in the uptake and transport of dietary fat, abdominal fluid balance, and gut immunosurveillance. Gut is closely connected to liver through the portal circulation. In several experimental and clinical studies, the 'gut-liver-axis' has been demonstrated to contribute to the pathogenesis of portal hypertension, liver cirrhosis, and its complications. Given a significant impact of gut health on the liver, in the current review, we highlight 'gut-liver axis' in context to the circulatory physiology of gut lymphatic vessels. Despite their paramount importance in maintaining fluid and immune homeostasis in the gut, gut lymphatic vessels remain one of the most understudied physiological systems in liver disease pathology. In the current review, we delineate the connections of gut lymphatics with abdominal fluid homeostasis and bacterial translocation in the pathogenesis of liver cirrhosis and portal hypertension. We describe mechanisms and factors that drive gut lymphangiogenesis and lymphatic vessel dysfunction during inflammation. The review also underscores the role of gut lymphatic endothelial cells in regulating gut and liver immunity. We finally discuss the prognostic and therapeutic prospects of studying gut lymphatic vessels in advanced liver cirrhosis.

Elevation of enterococcus-specific antibodies associated with bacterial translocation is predictive of survival rate in chronic liver disease

“…The gut-liver axis affects the progression of CLD and its complications, which leads to enhanced systemic inflammation 10.3389/fmed.2022.982128 via two routes (2). The first path carries bacterial products from the gut to the liver through portal circulation and eventually systemic circulation.…”

“…Fecal dysbiosis, small intestinal bacterial overgrowth, intestinal epithelial barrier dysfunction and increased permeability have been described as key events in patients with advanced chronic liver diseases (CLD) ( 1 ). Gut dysbiosis may contribute to translocation of pathological pathogen-associated molecular patterns including capsular polysaccharide (CPS), but a dysfunctional/leaky gut barrier plays a greater role, which has been shown to contribute particularly to bacterial translocation (BT) in alcohol-related cirrhosis ( 2 , 3 ). This gut-liver axis has been identified as a contributing factor to disease progression, increase of infection rates, development of complications, organ failure and generally poor outcomes related to CLD ( 3 ), although complex mechanisms remain poorly understood.…”

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

“…Clinically, liver cirrhosis comprises two stages as abovementioned: the fibrotic phase, often asymptomatic, also known as a compensated stage (CLC), and the cirrhotic phase or decompensated stage, characterized by complications arising from portal hypertension and hepatic insufficiency (DLC) [45,46]. The DLC is also considered a systemic disease because it affects most organs and systems of the body, including the immune system [47,48].…”

Lymphangiogenesis and Lymphatic Barrier Dysfunction in Renal Fibrosis

“…For digestive system, LVs intensify the trafficking of toxins from the gut to the systemic blood, enhancing immune reaction of the host, and thus contribute to the development of liver cirrhosis [8]. The increased number of LVs in heart appears to be beneficial in fibrosis of the cardiovascular system.…”