Removing Bile Acid Receptor in Gut Blocks Intestinal Inflammation

Mouse study could lead to ways to prevent disease

Rockville, Md. (August 15, 2024)-Removing a nuclear bile acid receptor that regulates glucose and lipid stability from the intestine blocked gut inflammation in mice, according to researchers at Children's Hospital Los Angeles. The findings are published in the American Journal of Physiology-Gastrointestinal and Liver Physiology. The article has beenchosen as an APSselectarticle for August.

The farnesoid (FXR) bile acid receptor plays a significant role in gut inflammation. This is the first documented case of FXR deletion protecting the intestinal barrier in multiple models of acute intestinal inflammation. Failure of the intestinal barrier has long been associated with body-wide infection (sepsis) that originates in the gut. Intestinal barrier protection is due to lowered inflammatory cells and maintenance of tight junctions linking the intestinal lining. When these cells do not stick together, intestinal contents leak into the abdominal cavity and other areas of the body, resulting in disease.

Gut inflammation can cause a number of health conditions, including ulcerative colitis and Crohn's disease. The effects are wide-ranging and include:

• Stomach pain
• Diarrhea
• Weight loss
• Anemia
• Loss of appetite

In this study, physiologists measured the amount of inflammation in the intestine after FXR was removed. Then, they used advanced microscopy to see the molecules that link epithelial cells and observe how a lack of FXR affects the intestinal barrier in the presence of disease. The lack of this receptor kept the gut barrier intact and prevented the animals from becoming sick.

"Inflammatory diseases of the intestine are a hallmark of many pathologies, including inflammatory bowel disease and gut-origin sepsis," said Christopher Gayer, MD, PhD, the study's lead author and chief of pediatric surgery at Children's Hospital Los Angeles. "The purpose of this research is to better understand the role of FXR within the intestinal epithelium which could help control and manipulate inflammation."

Read the full article, "FXR deletion attenuates intestinal barrier dysfunction in murine acute intestinal inflammation." It is highlighted as one of this month's "best of the best" as part of the American Physiological Society's APSselect program. Read all of this month's selected research articles.

NOTE TO JOURNALISTS: To schedule an interview with a member of the research team, please contact APS Media Relations or call 301.634.7314. Find more research highlights in our Newsroom.

Physiology is a broad area of scientific inquiry that focuses on how molecules, cells, tissues and organs function in health and disease. The American Physiological Society connects a global, multidisciplinary community of more than 10,000 biomedical scientists and educators as part of its mission to advance scientific discovery, understand life and improve health. The Society drives collaboration and spotlights scientific discoveries through its 16 scholarly journals and programming that support researchers and educators in their work.

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