Review: insights into the bile acid-gut microbiota axis in intestinal failure-associated liver disease-redefining the treatment approach

Background Intestinal failure-associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid-gut microbiota (BA-GM) axis contributes to the development of IFALD. Aims To review the BA-GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. Methods We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. Results The BA-GM axis demonstrates a unique IF signature manifesting as an increase in primary-to-secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA-GM axis showed promising potential in the management of IFALD. Conclusions Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA-GM axis may provide optimal clinical benefits and requires future investigation.

Automated summary

The bile acid-gut microbiota axis is crucial in the pathogenesis of IFALD, serving as potential diagnostic markers and therapeutic targets. A multitarget, individualized therapy focused on the BA-GM axis may provide optimal clinical benefits and warrants further investigation.