Roles of the inflammasome in the gut‑liver axis (Review).

Abstract

The gut‑liver axis connects the liver with the intestine via bile acid metabolism. Bile acid dysregulation leads to intestinal dysbiosis, that allows enterogenous pathogenic bacteria, including Gram‑negative bacteria and their products lipopolysaccharide (LPS), into the liver via the portal vein, triggering inflammation in the liver. The inflammasome serves as an intracellular pattern recognition receptor that detects pathogens or danger signals and mediates innate immunity in the liver or gut. Specifically, the NACHT, LRR and PYD domains‑containing protein (NLRP)6 inflammasome maintains intestinal microbial balance, by promoting interleukin (IL)‑18‑dependent antimicrobial peptide synthesis and mucus secretion from goblet cells. The NLRP3 inflammasome, in contrast, primarily induces IL‑1β and aggravates inflammatory liver injury. Furthermore, the NLRP3 inflammasome affects the epithelial integrity of cholangiocytes by inducing the production of pro‑inflammatory cytokines. In addition, bile acids, including deoxycholic acid and chenodeoxycholic acid, are able to activate the NLRP3 inflammasome in macrophages; however, bile acids have the potential to exert the opposite role by interacting with the membrane‑bound Takeda G‑protein receptor 5 or by activating nuclear farnesoid‑X receptor. Therefore, further investigation of the molecular mechanisms underlying the inflammasome, involved in the gut‑liver axis, may provide important insights into the identification of a potential therapeutic target for the treatment of liver and gut diseases. The present review discusses the roles of the inflammasome in the gut‑liver axis, and the emerging associations between the inflammasome and the intestinal microbiota or the bile acids in the gut‑liver axis.

• Authors: Junfeng Wang, Rui Dong, Shan Zheng
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 19 Issue 1 Pg. 3-14 (01 2019) ISSN: 1791-3004 [Electronic] Greece
• PMID: 30483776 (Publication Type: Journal Article, Review)

Chemical References

• Bile Acids and Salts
• Inflammasomes

Topics

• Animals
• Bile Acids and Salts (metabolism)
• Humans
• Inflammasomes (metabolism)
• Intestinal Mucosa (metabolism)
• Intestines (physiology)
• Liver (metabolism)
• Macrophages (metabolism)
• Signal Transduction (physiology)