Bile Acid Sensors for Cholestatic and Metabolic Liver Diseases, with Jessica Ferrell, PhD

Jessica Ferrell, PhD, assistant professor of integrative medical sciences at Northeast Ohio Medical University, sat down with HCPLive to discuss key takeaways from her presentation about primary sclerosing cholangitis (PSC), our current understanding of bile acids as metabolic sensors and activators of metabolic receptors, and areas where further research may be warranted.

Ferrell was a speaker during the session “AASLD Basic Science Symposium: Bile Acids at The Cross-Road of The Gut-Liver and Brain-Liver Axes” at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend, where she presented on the role of bile acid sensors in treating cholestatic and metabolic liver diseases.

“Bile acids themselves have been used to treat cholestatic and metabolic diseases for hundreds of years,” explained Ferrell. “They've really been used for a long time traditionally, but I think the more advanced role of bile acids now is understanding their roles as metabolic sensors and activators of metabolic receptors.”

Ferrell described the bidirectional relationship in which bile acids and the microbiome exist, noting how the gut microbes of the microbiome influence bile acid composition while bile acids themselves exhibit antibacterial and antimicrobial properties and can prevent dysbiosis and pathogenic bacterial overgrowth. She explained the relationship as “give and take” and “back and forth.”

Based on this knowledge of the more advanced role of bile acids and their bidirectional relationship with the microbiome, several clinical trials are currently ongoing to examine bile acids themselves and bile acid receptors as treatment for metabolic disease, MASLD, MASH, and alcohol-associated diseases.

“I think the biggest hope is to address the major increase in MASLD prevalence around the globe. Current estimates are that around 30% of the global population may be living with MASLD, which is typically considered a benign and reversible condition,” Ferrell explained. “We also don't really understand how patients progress to more serious liver disease, and so I think it's really important to target these bile acids and bile acid receptors at a reversible stage of disease so we can prevent irreversible and serious liver disease.”

During her portion of the session, Ferrell alluded to the use of bile acids and bile acid receptors for treating neurological disease, which she described as “something that people don't really think about that much.”

“These bile acids can actually exhibit anti-inflammatory effects and beneficial effects in the brain, not just in the liver and guts, so I think a new upcoming research area would be bile acids in neurological disease,” Ferrell said.

Still, she noted the main takeaway point from the session was bile acids remain relevant treatment targets for various liver and metabolic diseases and there's a lot that still needs to be explored regarding how bile acids and bile acid receptors work to mediate metabolism and liver cells.