Thirty years ago, scientists began researching the concept of multiple clocks in the digestive track. It has been a slow process with little research on the topic and little information has been gained until the last few years. We now know that multiple rhythms of the digestive tract exist and dictate healthy digestive function creating digestive breakdown if they are off. Last week’s newsletter Body Clocks and Weight Management – It’s All About Timing focused on the concept of how body clock function determines efficiency of metabolism. We now take a more in-depth look at gut clocks and their fundamental role in gut disorders. This has powerful implications for multiple digestive disorders like IBS, GERD, peptic ulcer disease, non-alcoholic fatty liver disease, obesity, and increased gut permeability, aka - Leaky Gut Syndrome.

The digestive tract has a rhythm called peristalsis. Peristalsis is the involuntary movement that pushes food thru the digestive tract. Peristalsis is highly dependant upon gut circadian rhythms and is far more complex than food simply passing thru a really long tube and coming out the other end completely unrecognizable. This gut circadian rhythm as well as the sensation of hunger and satiety comes from the central clock or pacemaker in the brain, i.e. the suprachiasmatic nucleus (SCN) of the brain’s limbic system. It receives information through neurological and hormonal (e.g. serotonin, ghrelin, cholecystokinin, motilin, and gastrin) signals found in the gut that then helps the gut’s rhythmic activity.

Related Disorders

There are several major areas of gut function that are affected by these circadian rhythms. These include gut motility, gastric acid secretion, maintenance and restoration of the protective mucosal barrier, production of digestive enzymes, nutrient transport in the small intestine, and the immunologic system of the gut. This has major implications for health across the board as you are what you eat, digest, detox, and respond to immunologically.

Researchers studying chronodisruption or the disruption or dampening of circadian rhythms due to shift work, sleep disruption, ambient light exposure at night, and aging are finding a link with gastrointestinal diseases. All of these activities or processes including aging are associated with a change in melatonin levels resulting in higher levels of oxidative stress or wear and tear. This chronodisruption affects the brain-gut communications and contributes to the development of GERD, gastric dyspepsia, peptic ulcers, inflammatory bowel syndrome and functional bowel disorders, non-alcoholic fatty liver disease, and even cancer of the gastrointestinal tract.

Leaky Gut Syndrome

The maintenance and restoration of the protective barrier in the digestive tract is a huge concept. The digestive tract has a surface area of about 3000 square feet or the size of a tennis court of which every inch has a highly complicated protective barrier more complicated than intense level security systems. A simple explanation of this extremely sophisticated system of the gut mucosa is that it is a barrier designed to prevent germs that we get from our food and environment and other metabolic waste products from entering into the body. At the same time, this barrier allows passage of nutrients into circulation to nourish the rest of the body. It does this with everything consumed throughout our entire life. This barrier has little doors called “tight junctions” and is regulated by a protein compound called zonulin. Zonulin tells the door to open or to close in the intestinal tract. It is vital to keep these tight junctions and zonulin of the mucosal barrier working well to keep inappropriate things from entering circulation from the digestive tract and causing stress.

When the door is inappropriately opened or damaged allowing wrong size particles to pass, it is called increased intestinal permeability, aka “Leaky Gut Syndrome”. It is considered an “open door for inflammation, autoimmunity, and cancer”. Leaky Gut Syndrome is associated with major diseases of many different types including neurodegeneration (Alzheimer’s, Parkinson, dementias, schizophrenia, and others), skin disorders, many types of arthritis, Celiac Disease, gluten intolerance, cardiovascular disease, autoimmune diseases, gut dysbiosis, food intolerances and allergies, mood disorders, and neoplastic disorders and many other health problems.

This is a major concept that mainstream medicine is finally starting to recognize and understand. Researchers are unraveling how these tight junctions and zonulin protein compounds work, how it applies, and why some develop illnesses and others don’t. Scientists have recently shown that circadian clock disorganization increases gut permeability.

Liver, Alcohol, Blood Sugar Metabolism – Oh My!

In another study, researchers looked at alcohol consumption which is known to cause injury to the intestinal barrier. They found that if the circadian rhythm was disrupted, there was more injury from the alcohol to the intestinal barrier as well as a higher risk for development alcoholic liver disease. Those who consume alcohol and have a history of sleep problems and IBS or other digestive concerns, may find themselves falling into a deep cycle of chronodisruption wreaking havoc on their health. It’s like an Alice in Wonderland effect – everything becomes distorted.

Researchers are also studying how the circadian clock plays a role in how the liver manages the metabolism of fats and carbohydrates. Intensive research has identified these principles and there are major concerns involving clocks, liver and metabolism. There is a significant number of genes in the liver that determine metabolic homeostasis or fitness that are turned on or off in response to balanced circadian rhythms. Certain receptors found in the liver for thyroid hormone and PPAR involved with glucose and lipid metabolism is also affected. The consequences of this disrupted metabolic rhythm in the liver results in development of metabolic syndrome, high blood sugar, high cholesterol, fatty liver disease and cirrhosis, and possibly diabetes mellitus.

GI Cancer

Researchers have also demonstrated that a disruption of the circadian rhythm may have a strong impact on the development of gastrointestinal cancer. The chronodisruption affects angiogenesis, cell proliferation, apoptosis and DNA repair in the gut. The researchers concluded that there are several findings with the gut clock and gastrointestinal tract cancer. Here are some of their conclusions. 1. Disruption of the gut clock due to shift work (working a rotating night shift at least 3 nights per month for 15 or more years) increases the risk of colorectal cancer. 2. Dampening or down-regulation of clock genes accelerates the development of tumors and may influence the response to anti-cancer drugs. 3. Circadian disruption has been shown with faster tumor growth and short survival in various studies. 4. Circadian clock genes regulate tumor cell proliferation or destruction 5. Clock gene polymorphisms or mutations are associated with an increased risk of cancer. 6. Effectiveness of chemotherapy drugs may be related with circadian based chemotherapy.

Natural Solutions

So now what? Your job requires shift work or traveling across the country, the tummy is in an uproar, your MD just told you your liver is getting a little fatty, and you’re not sleeping very well. On top of all that you just celebrated your birthday and you couldn’t see the cake with all the candles on top of it. There are some very basic things to focus on and then also there are more sophisticated support tools. The human body needs to keep a schedule. Whatever you can do to maintain a consistent meal pattern, sleep-wake pattern, and an exercise patterns are fundamental to the body clocks. Exposure to bright light, ideally sunlight or full spectrum lighting first thing in the morning sets the start point for the day. Open the shades or turn on full spectrum lights. This sends powerful signals to the SCN in the brain for orchestrating rhythms. Conversely at bedtime and ideally even a couple hours before, remove exposure to bright lights and ambient lighting in the bedroom. This helps the normal production and release of melatonin. Individual often find that the trip to the cabin where they unplug from late nights and bright lights, they feel their bodies unwinding, the sleep is delicious, and the body just has this sense of getting balance. While some will say this is simply due to removal of external stress, we now know there may be something deeper to this.

The Leptin Diet lifestyle cannot be emphasized enough. As you read earlier in this newsletter, ghrelin, cholecystokinin, and many other digestive hormones require a circadian rhythm to function properly. If one grazes, skip meals, or the weekends are thrown off by sleeping in, this leads to chronodisruption in the gut. Eating late at night must be avoided.

For individuals dealing with gastric bypass, banding, or other digestive weight loss surgeries, gut clocks and its rhythm are apt to become quite handicapped with metabolic clock efficiency. This will happen not only because of the inability to eat more than a couple ounces of food at a time, requiring multiple small meals per day, but also theoretically due to the section of stomach that was removed mediates some of the clock signals. While there are no research studies on the concept of gut clocks and gastric bypass, common sense tells you that disrupting clocks and neuroendocrine hormones in the digestive tract from the bariatric procedure is going to be consequential rhythmic disruption. This is going to be a major conundrum facing these individuals. They will have to work that much harder at restoring other rhythms in their body and being proactive with reducing the expression of oxidative stress.

Researchers clearly recommend improving melatonin levels for gut chronodisruption. Melatonin has been found to be beneficial in regulation functional motility disorders and reducing acute inflammation in disorders like IBS, GERD, Peptic Ulcer Disease, gastritis, and even acute gastric hemorrhage. Melatonin also acts as a powerful antioxidant that helps down-regulate oxidative stress that occurs when the body clock is off. It is vital to the master clock (SCN) function.

If you suffer from GERD, IBS, have a family risk history of colon, stomach, or other gastrointestinal cancers, metabolic syndrome, non-alcoholic or alcoholic fatty liver disease, Leaky Gut Syndrome, etc. you must understand this fundamental concept of body clocks and disease expression. Chronodisruption also opens the door for profound implications with diseases and management. In this case – timing is everything!