by Matt Batcheldor
A research team at Vanderbilt University Medical Center led by Matthew Freiberg, MD, MSc, professor of Medicine and Dorothy and Laurence Grossman Professor of Cardiology, has received a $7 million grant from the National Institutes of Health (NIH) to understand how alcohol’s effect on the gut microbiome drives heart disease.
The team will study alcohol-associated changes in gut bacteria, also known as gut dysbiosis or leaky gut. Excessive alcohol use leads to leakage of gut bacteria and their products in the peripheral circulation, which is associated with multiple problems, including cardiovascular disease (CVD) and early death. This is an especially big problem in people who are already at high risk for CVD, such as those with HIV infection who drink heavily. The program project grant is distributed by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the NIH.
Freiberg and his team are studying whether probiotics — healthy bacteria contained in capsules that patients take by mouth —can help reduce risk of CVD.
The team will administer tailored probiotics or placebo to 250 people with HIV who are heavy drinkers. These probiotics contain bacteria that make butyrate, a bacterial product that is helpful to the enterocytes (cells lining the gut).
Study participants will be given a daily dose of the probiotic supplements or placebo for six months, and the team will study whether it stops leakage of gut bacteria and associated immune responses and related cardiovascular disease risk.
“In this randomized controlled trial, we are studying whether manipulating the gut microbiome with probiotics, as compared to placebo, can reduce alcohol-related gut damage,” Freiberg said. “In a second, larger study involving thousands of patients, we are attempting to quantify the extent of cardiovascular damage associated with very high levels of gut dysbiosis metabolites.
“That study will have greater statistical potential to associate leaky gut with clinical outcomes, such as having a heart attack, heart failure or peripheral arterial disease 10 years later,” Freiberg said.
This separate cohort will come from the Veterans Aging Cohort Study, an observational cohort of veterans with and without HIV.
If these tandem projects are successful, Freiberg said the next step would be to seek a large, 5,000- to 10,000-participant study to alter the gut bacteria of patients over a longer period, such as two to five years, to definitively study the efficacy of probiotics in reducing CVD events. If successful, giving tailored probiotics to such patients may become an important new therapy for people who are heavy drinkers at risk for heart disease, Freiberg said.
“The advantages of this intervention are several-fold,” he said. “We’re not giving you something new; we’re giving you something you already have, but you’re losing it. The body isn’t experiencing a new thing, per se. It’s not that expensive. In some cases, it could be a dollar a day. Also, these pills can be tailored to the individual patient’s needs.”
The study is a collaboration between Vanderbilt and multiple centers, including the University of Louisville, Veteran’s Administration, Yale University, Baylor College of Medicine, Boston University and Pavlov State Medical University in St. Petersburg, Russia, where the population of heavy drinkers with HIV infection will be studied.