Prioritizing Gut Health, Bile Acid Research in Liver Disease Care

As previously covered in the first segment of an interview with HCPLive, the function and role of bile acids in hepatic disease is an emerging field of research that warrants more investment and clinical application.

A key question experts are trying to answer in current research is the causative versus correlative nature of the protein class in not only liver, but gut health in general.

In the second segment of a panel interview during The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend, a trio of scientists working in the field of liver research discussed strategies and avenues to apply bile acid research into clinical care strategies. The experts included:

• 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

Zhou highlighted recent research by her colleagues that which attempted to profile the role of not only serum bile acid, but microbiome-mediate bile acid, in patients with non-alcoholic steatohepatitis (NASH).

“So we already have interesting data which is indicating specific compositions of the bile acids, which is associated with liver disease,” Zhou said. “So overall, you can see that this regulation of bile acid, but if you compare NASH and an alcohol liver disease patient…then we can already see some of the trend of bile acid profiles that are specific to NASH or alcohol-related liver disease. So I think this is the starting point.”

Zhou explained that more broad and robust patient data is needed to help distinguish bile acid profiles, in order to tailor panels that would help identify biomarkers for one hepatic disease over another, as well as an understanding of disease prognosis.

Guo mentioned that only about 20% of know human bile acid types are adequately profiled—“but what are the rest of the bile acids doing in our body?

“What type of association algorithm should this develop in the future to put bile acids into the diagnosis, prognosis, or maybe even treatment?” Guo suggested. “It’s very sad—many of the drugs targeting bile acids right now either failed or stopped at early stage, but this is because the understanding of bile acids is not profound.”

Barbier highlighted a segment of the group’s symposium at The Liver Meeting which discussed the relation of bile acids and the microbiome, and how targeting the microbiome may help “not only in discerning the bile acids in liver disease progression, but also in further understanding how this bile acid can be used as a drug treatment.”

Another segment of the symposium discussed the alteration of the microbiota functioning to positively influence liver disease, Barbier mentioned.

On the subject of promoting better gut health in patients with liver disease, Zhou noted the challenges seen in disease spaces like C difficile, which turned an infection exacerbated by harm to the gut into an opportunity to develop highly effective live microbiota therapy.

“We still have a lot of questions about how we can control and make sure these treatments—which are really beneficial for the patients…we still have a lot of work to do in understanding the entire community in the gut, and not only bacteria,” Zhou said. “We also have other micro-organisms—these are really determining the entire consequence in the gut.”

A key component of unlocking the means to aiding patients with an informed understanding of bile acids is in better understanding its interaction overall with the microbiome.

“Secondary or tertiary bile acids are made in the microbiome; the appearance of certain classes of secondary bile acids in the circulation—are they really doing something to the body or are they actually reflecting the functions of the microbiome, especially in the gut?” Guo said.