by Kristin Hoddy, PhD
Postdoctoral fellow in the Department of Medicine
Section of Pulmonary and Critical Care
A good night’s sleep is not always easy. Lack of sleep may serve as badge of honor, a sign of productivity, or, a necessity—to get a job done. The number of sleepless Americans seems to be steadily increasing.
Poor sleep is not just a problem for night-owls. Approximately 24 to 50 percent of middle aged men and 9 to 23 percent of middle aged women face the day with a poor night’s sleep due to sleep-disordered breathing, a catch-all term that includes conditions like sleep apnea. The risk is higher in certain populations, including the elderly, those with high blood pressure or obesity, and those with a family history.
When the airway is repeatedly restricted, sleep disordered breathing occurs, causing a drop in blood oxygen, blood pressure fluctuation, and widespread stress. The brain senses the change in oxygen level and triggers arousal, a “wake-up now!” response, which generally lasts three to fifteen seconds; longer arousals typically cause the person to awaken fully.
This condition can go undetected and persist for years, but those affected may feel poorly rested and have trouble remembering things. As few as five arousals an hour may be enough to cause a person to feel chronically sleepy; some people with severe cases experience an average of 30 arousals hourly. Left untreated, the combination of low blood oxygen levels and poor sleep can have a disastrous effect on health, wellbeing—and potentially the gut microbiome.
Both population studies and experimental studies have shown a provocative connection between inadequate sleep and increased risk of both obesity and diabetes. “Good sleep is important for maintaining optimal health, but people don’t always realize the impact that sleep has,” says Erin Hanlon, PhD, from the University of Chicago Sleep Research Center.
Seminal work led by UChicago researcher Eve Van Cauter, PhD, showed that sleep deprivation hinders the body’s ability to control blood sugar. In fact, after about a week of sleeping only four hours a night, study participants showed their first meal of the day elicited peak blood sugar responses akin to aging about 30-40 years.
Interrupted breathing presents a major barrier to sleep quality. Every time an arousal occurs, the sleeper goes back to stages of lighter sleep—problematic, because the brain needs to cycle through specific sleep stages each night. In just three nights where subjects’ deepest sleep was disrupted, researcher Esra Tasali, MD, found a 25 percent decline in insulin sensitivity—a hallmark of type two diabetes—similar to gaining between 17 and 27 pounds.
“The mechanisms between sleep loss, body weight, and blood sugar control are not well understood,” Hanlon says. “Sleep loss might be affecting the function of the microbiome which, in turn, influences body weight and glucose regulation. It could possibly be the other way around, or perhaps a multi-directional relationship.”
A recent paper published by a UChicago team with international collaborators provided some clarity. They compared two groups of mice for four weeks, repeatedly disrupting sleep every two minutes (as in severe sleep apnea) in one group while the other slept undisturbed. Mice with repeatedly disrupted sleep demonstrated increased appetite, diminished insulin sensitivity, and an accumulation of fat concentrated underneath the abdominal muscles and around the organs in the gut. This particular fat also showed indications of elevated inflammation. The researchers noted changes in both the type of bacteria and the metabolic products those bacteria produced. Despite these interesting relationships, the exact mechanisms were unclear.
The team went on to create a model with cells that mimicked intestinal barrier tissue, the tissue critical for keeping waste and bacteria in the intestine while letting nutrients pass through. They exposed the model tissue to intestinal contents from both mouse groups. The tissue grown from sleep-disrupted mice proved to be leaky; that from the well-rested mice held its own.
Next, the team inoculated germ-free mice with microbiota from each of the mouse groups. The germ-free mice given bacteria from the sleep-disrupted group increased their food intake and went on to develop tell-tale signs of inflammation and insulin resistance—despite no disruption to their sleep and no change in body weight or visceral fat.
This work provides some tantalizing clues to the consequences of disrupted sleep, which raises some practical questions. Would a healthy gut microbiome protect against the development of obesity or diabetes in the face of a sleep-deprived world? Perhaps the answer to sound sleep is waiting deep within our guts.