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Health Information Under the Microscope: Connecting Sleep-Wake Cycles, Leaky Gut and Liver Disease

Could a liver condition in alcoholics offer clues to help those with allergies and asthma? Could sleep-wake cycles be related to intestinal permeability, which is also known as leaky gut? Researchers at Rush think so, which is why they are investigating the science behind alcohol-induced intestinal permeability.

Alcoholic Steatohepatitis and Leaky Gut
Thirty percent of alcoholics suffer from steatohepatitis Characterized by swelling of the abdomen, weight gain and loss of appetite, this liver disease can lead to cirrhosis, a life-threatening condition.

For alcoholic steatohepatitis (ASH) to occur, toxins must be released into the bloodstream by escaping the lining of the intestines, an escape made possible by increased permeability of the intestines, or leaky gut.

"What we wonder is why only some alcoholics are susceptible to ASH and the gut leakiness that can lead to it," says Christopher Forsyth, PhD, a researcher at Rush. Puzzled by this, he and other investigators at Rush collaborated to answer questions that could ultimately lead to an explanation and perhaps offer clues about ways to protect against ASH and other conditions that have been associated with intestinal permeability, such as allergies, asthma and even autism.

Exploration in the Laboratory
To help put the pieces of the puzzle together, the researchers— including gastroenterologists Garth Swanson, MD, and Ali Keshavarsian, MD — went to the laboratory to evaluate the relationship between alcohol, intestinal genes that can affect circadian rhythms controlled by the brain and gut leakiness.

They based their hypothesis of a relationship among these elements on previous research regarding the brain-gut connection and its possible role in causing gut permeability. They also applied their knowledge of how the intestinal "clock" genes interact with the brain's master clock. Intestinal circadian genes, they knew, play a role in sending signals to the body’s master clock in the brain, which controls the body's circadian rhythm — physical, mental changes that follow a 24-hour cycle— and keeps body functions in sync. Sleep-wake cycles, hormone release, body temperature and other important body functions all follow the circadian rhythm. Outside factors, such as physical and psychological stress, can affect the circadian rhythms that are controlled by the brain.

Brain, gut, circadian rhythms: They are all connected. Exactly how or why, however, isn't completely clear.

But by tweaking the intestinal circadian clock genes in tissue samples, the researchers found that alcohol could induce increases in gut permeability, or gut leakiness. They also found direct evidence showing that circadian genes have a central role in regulating intestinal permeability.

While further study is warranted, these findings suggest that disruptions or variations in alcoholics' sleep-wake cycles could account for the differences in susceptibility to ASH. This knowledge could lead to therapeutic approaches to prevent "leaky gut" (and the ASH that can result from it) not only in alcoholics but other people as well.

More Information at Your Fingertips …
  • Watch a video of gastroenterologist Garth Swanson, MD, and hear why helping patients get better is so important to him.
  • Watch a video of gastroenterologist Ali Keshavarazian, MD, and hear him discuss why gastrointestinal problems are often sensitive, hard-to-discuss topics.
  • Looking for a gastrointestinal specialist? Call (888) 352-RUSH (7874) or visit the University Gastroenterologists home page on the Rush website.
  • Stay in touch with Rush with Rush News Blog, Rush InPerson, Facebook, Twitter and YouTube.
Please note: All physicians featured in Discover Rush Online are on the medical faculty of Rush University Medical Center. Some of the physicians featured are in private practice and, as independent practitioners, are not agents or employees of Rush University Medical Center.

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Under the Microscope: Connecting Sleep-Wake Cycles, Leaky Gut and Liver Disease

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