Many patients with alcoholic pancreatitis continued to drink during COVID-19. Researchers at the University of Miami Miller School of Medicine are studying the effects of long-term alcohol consumption and looking for better treatments for alcohol-related pancreatic diseases.

Researchers are looking for solutions to further consequences of alcohol use, its harmful effects and treatment. Understanding the mechanisms of alcohol abuse has gained importance, especially in the wake of the COVID-19 pandemic. Greater alcohol consumption has led to an increased burden of pancreatic disease in society.

In a study titled “Urolitin A reduces the severity of chronic pancreatitis is associated with chronic alcohol use by inhibiting PI3K/AKT/mTOR signaling,” published in American Journal of Physiology – Physiology of the Gastrointestinal Tract and LiverResearchers are studying the short- and long-term effects of this increased alcohol exposure on pancreatic disease and are working together on innovative approaches to better understand how to treat patients with pancreatitis who continue to drink alcohol.

Pancreatitis is inflammation of the pancreas, often associated with long-term alcohol consumption, a potential risk factor for acute pancreatitis. Repeated attacks of acute pancreatitis lead to chronic pancreatitis. According to statistics published by the National Institute of Diabetes and Digestive and Kidney Diseases, about 275,000 hospitalizations for acute pancreatitis and 86,000 for chronic pancreatitis occur each year in the United States.

Acute pancreatitis appears suddenly and in most patients can resolve within a few days after treatment. However, in some cases, acute pancreatitis can also cause severe, life-threatening conditions. Repeated episodes of acute pancreatitis cause permanent damage to the pancreas, causing weight loss, pain, diabetes and even pancreatic cancer.

Alcohol consumption has exploded during COVID-19

Total alcohol sales in the US have nearly tripled during the COVID-19 pandemic, leading to an increase in the number of patients diagnosed with alcohol-related pancreatitis. Excessive alcohol consumption is associated with 40-70% of cases of pancreatitis. Without moderation, alcohol consumption has a profound effect on the liver and pancreas, causing fat storage and inflammation, disrupting normal function.

With repeated episodes of binge drinking (four to five drinks in two hours), the pancreas eventually creates scar tissue with permanent inflammation, impairing its endocrine and exocrine functions needed to digest food and regulate blood sugar. This chronic organ damage can cause excruciating pain, malnutrition, diabetes and death.

“We are developing new models to study and prevent inflammation or reverse damage to the pancreas caused by excessive alcohol consumption,” said lead author Nagaraj Nagatihali, PhD, assistant professor of surgery in the DeVita Dotry Department of Family Surgery. surgical oncology.

Chronic alcohol consumption perpetuates pancreatic damage in mouse models

Accumulating scientific evidence suggests that long-term alcohol consumption in acute alcoholic pancreatitis causes permanent damage to the pancreas due to recurrent episodes acute pancreatitis contributing to a continuous fibro-inflammatory microenvironment in the pancreas.

” molecular mechanisms participation in the pathophysiology of alcoholic pancreatitis with continuous alcohol intake remains ambiguous; treatment options and prevention strategies are limited by limited experimental animal models that successfully recapitulate human pancreatitis resulting from chronic or continuous alcohol consumption after established pancreatic injury,” said Dr. Nagatihali.

“In this study, using an established murine model of alcoholic pancreatitis, we addressed two major unanswered questions regarding the pathogenesis of pancreatitis. We characterized the signaling pathways specific to the pancreas in this process and determined whether new therapeutic agents should be used. may attenuate the progression of alcoholic pancreatitis despite ongoing alcohol triggers,” said study first author Siddharth Mehra, Ph.D., a postdoctoral fellow in the Miller School’s Department of Surgery.

Prevention of chronic alcohol-related pancreatitis may benefit patients with difficulty abstaining from alcohol

The microbiome has been implicated in gastrointestinal inflammation as a critical mediator of overall gut health. Uralitin A is a naturally occurring compound synthesized by intestinal bacteria from ingested ellagitannins, a class of hydrolyzable tannins found primarily in pomegranates, berries, and nuts. Previous work by the group has shown that urolithin A is a potent anti-inflammatory agent in several preclinical disease models and exhibits antitumor activity in gastrointestinal cancer.

“Our studies have shown that urolithin A is well tolerated and does not cause any side toxic effects at clinically relevant doses in mice. However, despite the promising effect of urolithin A in several malignant tumors and inflammatory diseases, the benefit of this microbial metabolite in the prevention of pancreatitis is not researched,” says Dr. Nagatihali. The FDA recognizes Urolithin A as a “safe dietary supplement.”

“U animal experimentswe have shown that urolithin A can help to increase the effectiveness of the treatment of alcoholic pancreatitis, despite the continued alcohol consumption,” said Dr. Mehra.