Toll-Like Receptors Recognize Intestinal Microbes in Liver Cirrhosis

Abstract

Liver cirrhosis is one major cause of mortality in the clinic, and treatment of this disease is an arduous task. The scenario will be even getting worse with increasing alcohol consumption and obesity in the current lifestyle. To date, we have no medicines to cure cirrhosis. Although many etiologies are associated with cirrhosis, abnormal intestinal microbe flora (termed dysbiosis) is a common feature in cirrhosis regardless of the causes. Toll-like receptors (TLRs), one evolutional conserved family of pattern recognition receptors in the innate immune systems, play a central role in maintaining the homeostasis of intestinal microbiota and inducing immune responses by recognizing both commensal and pathogenic microbes. Remarkably, recent studies found that correction of intestinal flora imbalance could change the progress of liver cirrhosis. Therefore, correction of intestinal dysbiosis and targeting TLRs can provide novel and promising strategies in the treatment of liver cirrhosis. Here we summarize the recent advances in the related topics. Investigating the relationship among innate immunity TLRs, intestinal flora disorders, and liver cirrhosis and exploring the underlying regulatory mechanisms will assuredly have a bright future for both basic and clinical research.

The Immune System through the Lens of Alcohol Intake and Gut Microbiota

“…B cells mature into plasma cells that produce antibodies (immunoglobulins, Ig), eliminating extracellular microorganisms and preventing the spread of infection [15,16] (Figure 1A). Both the innate and the adaptive immune system influences and shapes the composition and diversity of the gut microbiota [17], whereas the gut microbiota modulates the immune system via different metabolites and activation of TLRs signaling pathways [18].…”

Gut Microbiota—A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review

“…A 40% reduction in microbiome diversity was associated with low-grade systemic inflammation and adipokines production, mainly mediated by LPS production [ 63 ]. Similarly, other bacterial products may elicit inflammation and insulin resistance, activating the toll-like receptor (TLR) pathway [ 64 ]. The SCFA production also has a direct effect on insulin resistance, as butyrate and propionate may modulate gluconeogenesis and de novo lipogenesis [ 65 ].…”

Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001–2023)

“…In addition, TLRs can recognize the gut microbiota in cirrhotic patients, triggering signaling cascades linked with the progression of cirrhosis. TLRs hold a crucial position in the occurrence, development, and treatment of cirrhosis ( Fan et al, 2021 ). Furthermore, the gut microbiota and TLR4 are proposed as significant therapeutic targets to prevent hepatocellular carcinoma in individuals with severe liver conditions ( Darnaud et al, 2013 ).…”