Bile Acids in Gut, Brain and Liver Health: What Do We Know?

A daylong session at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend, sought to introduce hematologists and other specialty clinicians to the true impact and implication of bile acids in their patients. A common target for new and developing therapies in the space, bile acid remains a lesser prioritized barometer for patient status—and a potentially unheralded key to understand the interplay of gut, liver and central nervous system health.

In a panel discussion with HCPLive during The Liver Meeting, a trio of experts explained the design and intent of the conference symposium, “Bile Acids at The Cross-Road of The Gut-Liver and Brain-Liver Axes.” The panel included these experts:

• Grace Guo, MBBS, PhD, Assistant Professor, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University
• Huiping Zhou, PhD, MS, Professor, Department of Microbiology and Immunology, Medical College of Virginia, VCU
• Olivier Barbier, PhD, Research Center of the University of Laval, Quebec

“What we wanted to do when we wrote the agenda for this session was to make the audience realize bile acids are not only working in the liver,” Barbier explained to HCPLive. “These are hormones that work also in tissues such as in the gut and also the central nervous system.

Evidence is growing to indicate that bile acid receptors can influence several physiological and biological processes in the brain, Barbier said.

Zhou discussed her personal evolving understanding of bile acid, noting it wasn’t until recently when new bile acid receptors were identified that she and colleagues began to expand their view on function and influence on particular diseases.

“So, for a long time people only think of bile acids as just a detergent—it only helps us for nutrient absorption—until we realized that they are very important signaling molecules,” Zhou said. “They not only can activate the nuclear receptors, but we’ve also identified the G protein-coupled receptor.”

The discoveries have expanded the field to introduce potential new agents for hepatic disease, including FXR agonists, TGR5 receptor agonists, and FX-TGR5 dual agonists.

“I think this has really expanded the view for the functioning of bile acids and how they are linked to different diseases,” Zhou said. “At the very beginning, you would think metabolic disease is very important. But also, the organ cross-talk is very important, especially in terms of the bile acids in intrahepatic circulation, which is constantly linked between the liver and gut.”

Guo noted these discoveries are not too far from the observation that bile acids are endocirne molecules, just about 30 years ago.

“But now we also are getting into organ crosstalk and cell crosstalk mediated by bile acid or bile acid-activated pathways,” Guo explained. “Basically, bile acids are involved in the development of cholestasis, liver cancer, inflammatory bowel disease, gallstones, Parkinson and Alzheimer disease, and alcoholic liver disease.”

Though investigators remain uncertain whether this involvement is causative or associative, it warrants further investigation—as does the potential discovery of more bile acid types. There are currently approximately 140 known to exist in living creatures, and 40 specifically in humans, Guo said.

With the progression of this research, the panel emphasized the need for discovery to be reflected in real-world applications.

“We don’t even really put bile acids into the clinical practice right now—you look at the entire biochemical panel, no one is profiling bile acids,” Guo said. “If you look at patients’ liver status, nobody is really looking at their hepatic bile acid circulation, which is surely important for the study of bile acid biology, physiology and pathology.”