A new study shows that a single drinking binge — roughly four drinks for women or five for men within about two hours — can weaken the gut lining, making it less able to perform one of its core jobs: keeping bacteria and toxins from entering the bloodstream, a phenomenon known as “leaky gut.”

Now, investigators at Harvard and Beth Israel Deaconess Medical Center have identified how binge drinking damages the gut, and why those leaks in the system may set off harmful inflammation long after the last drink is poured.

The findings are published in Alcohol: Clinical and Experimental Research.

Led by first author Scott Minchenberg, a clinical fellow in gastroenterology and hepatology at BIDMC and instructor in medicine at Harvard Medical School, the scientists examined how short bursts of high-dose alcohol affected different parts of the gut. Their findings suggested that even brief episodes of heavy drinking cause injury, calling in cells normally reserved for fighting invading germs to the lining of the gut.

Certain immune cells — neutrophils —  can release web-like structures known as NETs that directly damage the upper small intestine and weaken its barrier, helping explain the leaky gut that can let bacterial toxins slip into the bloodstream.

When the researchers blocked the NETs using a simple enzyme to break them down, they observed a reduced number of immune cells in the gut lining and less bacterial leakage; that is, the enzyme prevented gut damage.

“We know that excessive drinking can disrupt the gut and expose the liver to harmful bacterial products, but surprisingly little was known about how the upper intestine responds in the earliest stages,” said corresponding author Gyongyi Szabo, professor of medicine at Harvard Medical School and chief academic officer at BIDMC and Beth Israel Lahey Health. “Our study shows that even short bouts of binge drinking can trigger inflammation and weaken the gut barrier, highlighting a potential early step in alcohol-related gut and liver injury.”

The research was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.