Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation

Area of Science:

• Immunology
• Gastroenterology
• Endocrinology

Background:

• Bile acids are crucial signaling molecules that activate specific receptors.
• Key receptors like Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) are known to modulate inflammation in liver and gut diseases.
• The role of other bile acid-responsive receptors in inflammatory conditions is an expanding area of research.

Purpose of the Study:

• To review recent advancements in understanding the immune-modulatory functions of bile acid-responsive receptors.
• To explore the involvement of specific receptors including Sphingosine-1-phosphate receptor 2 (S1PR2), Pregnane X receptor (PXR), Constitutive androstane receptor (CAR), Vitamin D receptor (VDR), and Retinoic acid-related orphan receptor γt (RORγt).
• To discuss the contribution of microbiota-derived bile acids to intestinal and hepatic inflammation via these receptors.

Main Methods:

• Literature review of recent scientific publications.
• Synthesis of current knowledge on bile acid signaling pathways.
• Analysis of the interplay between gut microbiota, bile acids, and immune responses.

Main Results:

• FXR and TGR5 are established modulators of inflammation in conditions like hepatitis, cholestasis, and inflammatory bowel disease.
• Evidence is emerging for the immune-regulatory roles of S1PR2, PXR, CAR, VDR, and RORγt in response to bile acids.
• Microbiota-derived bile acids play a significant role in mediating intestinal and hepatic inflammation through these various receptors.

Conclusions:

• Bile acid-responsive receptors represent a complex network influencing inflammatory processes.
• Targeting these receptors and modulating the gut microbiota offers promising avenues for novel therapeutic strategies against inflammatory syndromes.
• Further research into these pathways can lead to innovative treatments for chronic inflammatory conditions.