The Gut–Circadian Rhythm Connection

In past articles, I’ve covered the importance of the circadian rhythm to good health. I’ve also written a lot about the gut microbiome. But you may be surprised to learn that gut bacteria can directly influence your circadian rhythm. Imbalances in your gut can disrupt your circadian rhythm and affect your sleep, hormones, and immune system. Read on to learn more about how these two systems are interconnected and how you can keep your gut and “body clock” happy.

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What Is the Circadian Rhythm?

The term “circadian rhythm” refers to the internal organization of biochemical processes within our bodies that follows an approximately 24-hour cycle and regulates many aspects of our behavior and physiology. Our circadian rhythms are produced by collections of genes and proteins within our bodies that exhibit rhythmic activity and are referred to as “body clocks.”

The “master” body clock is a structure in the brain called the suprachiasmatic nucleus (SCN). Additional body clocks, called “peripheral body clocks,” are distributed throughout organs such as the liver and pancreas. The master clock in the SCN regulates the activities of peripheral clocks, and the peripheral clocks interact with one another and provide feedback to the master clock. Together, these internal timekeepers generate our circadian rhythms, which affect many important aspects of our health such as our sleep/wake cycles, hormone balance, and metabolism (1).

Could the bacteria in your gut be throwing off your circadian rhythms? #microbiome

To keep our bodies running “on schedule,” our body clocks need to be synchronized with each other. Cues from our external environment such as light, temperature, and food intake sync our body clocks, initiating circadian rhythms. Depending on what cues we provide our bodies, and when we provide the cues over the course of a 24-hour circadian cycle, we either keep our body clocks ticking in synchrony or throw a wrench into their cyclical processes, creating circadian rhythm disruption. Circadian rhythm disruption has been linked to many disease processes, including metabolic syndrome, obesity, cardiovascular disease, intestinal dysbiosis, inflammatory bowel disease, neurodegenerative disease, and cancer (2, 3) (4).

Intestinal Cells Undergo Circadian Rhythms

The “master” body clock in the SCN and the peripheral clocks in the liver and pancreas have long been considered the primary regulators of circadian rhythms. However, it was recently discovered that cells in the intestine also undergo circadian rhythms (5). Intestinal cell circadian rhythms influence gut motility, nutrient absorption and metabolism, and cell proliferation (6, 7, 8). Perturbation of the circadian rhythm caused by abnormal sleep/wake cycles renders intestinal cells more vulnerable to injury. Considering this information, it is not surprising that research has found circadian rhythm disruption to be linked to gastrointestinal diseases such as irritable bowel syndrome and colorectal cancer.

Gut Microbes Have Their Own Circadian Rhythms

The circadian rhythms in the gut are not limited to intestinal cells; it turns out that gut microbes also play a key role in the regulation of circadian rhythms. The collection of microbes that resides in your gut undergoes its own circadian rhythms every 24 hours. These circadian rhythms involve changes in the location of gut microbes within the intestine, fluctuations in their adherence to the intestinal wall, and variations in their production of metabolites such as short-chain fatty acids, which modulate gene expression and biochemical pathways both locally in the gut and systemically throughout the body. Through these cyclical mechanisms, the circadian rhythms of gut microbes ultimately affect our own circadian rhythms, which regulate our sleep/wake cycles, hormone release, and metabolism (9). In addition, our circadian rhythms provide feedback to our gut microbes.

The Gut and Circadian Rhythms Are Tightly Linked

Our circadian rhythms are therefore linked to the rhythms of our intestinal cells and gut microbes in a multi-directional feedback loop. Factors that influence the integrity of the gut and the microbiome therefore affect our circadian rhythms, and vice versa. Taking steps to “synchronize” the rhythms of our gut microbiome with our other circadian rhythms, such as sleep/wake cycles and food intake patterns, appears to be crucial for preventing diseases associated with circadian disruption, such as metabolic syndrome, obesity, cardiovascular disease, and cancer.

Diet and Meal Timing Affect Circadian Rhythms

While light exposure and temperature are the primary cues that affect the master body clock in the brain, intestinal and gut microbe circadian rhythms are primarily influenced by the timing of food intake and composition of the diet. Diet-induced dysbiosis and erratic meal consumption disturb both intestinal cell and gut microbe circadian rhythms and have systemic effects on the body (10).

A study in which mice were fed a high-fat, high-carb diet loaded with polyunsaturated fats and processed sugars (designed to mimic the Standard American Diet) experienced profound disruptions in their intestinal and gut microbe circadian rhythms. These disrupted rhythms altered microbial metabolite production, which led to disorganized gene expression in the mice’s body clocks. The disordered gene expression down-regulated the mice’s metabolism, causing them to develop dysfunctional glucose homeostasis, hypercholesterolemia, and obesity (11). This research suggests that a high-fat, high-carb SAD blunts gut circadian rhythms and has systemic effects on body clocks that control metabolism. Conversely, a diet that is low in processed sugars and polyunsaturated fats and rich in EPA, DHA, and antioxidants has been shown to normalize gut circadian rhythms (12, 13, 14).

Erratic eating patterns, such as skipping meals and eating late at night, can also disrupt intestinal cell and gut microbe circadian rhythms. However, temporal modification of eating behaviors has been shown to normalize gut microbe rhythms. Time-restricted feeding, a practice in which eating is only allowed during a certain window of time each day, has been found to normalize aberrant gut microbe rhythms and reverse some of the negative effects associated with circadian disruption, such as insulin resistance (15).

This research suggests that shifting away from the Standard American Diet and instead consuming a whole-foods-based diet low in polyunsaturated fats and sugars and high in antioxidants may be key for normalizing circadian rhythms and preventing diseases associated with circadian disruption, such as metabolic syndrome and obesity.

Antibiotics Disrupt Gut Circadian Rhythms

Antibiotic use has been found to disrupt circadian rhythms in animals by impairing the circadian activity of their gut microbes. Ultimately, this leads to an uncoupling of overall circadian rhythms in the host (16). However, restoration of gut microbes via prebiotics and probiotics may help restore normal circadian rhythms.

Sleep Affects Gut Circadian Rhythms

Chronic sleep disruption—which can include waking multiple times per night, shift work, or chronic jet lag from frequent travel—alters the rhythms of gut microbes and has been linked to detrimental changes in metabolism such as insulin resistance and obesity (17). This suggests that practicing “sleep hygiene” may help us normalize both our own circadian rhythms and the rhythms of our gut microbes.

Examples of sleep hygiene practices include avoidance of blue light and excessive artificial light at night, powering down electronic devices a couple hours before bed, sleeping in a cool room, and ceasing to eat several hours before bed. These practices sync the body clock in the suprachiasmatic nucleus and send signals to the brain to produce melatonin, the hormone that helps us fall asleep. Melatonin, in turn, helps regulate the rhythms of our gut bacteria (18).

Disrupted Circadian Rhythms and Gut Disorders

Disrupted circadian rhythms, both those originating in the gut and those produced by the SCN, can increase the risk of developing gut disorders.

Circadian disorganization induced by abnormal sleep/wake cycles combined with a “Westernized diet” high in processed carbs and damaged fats has been linked to the development of inflammatory bowel disease (IBD) (19). Disruption of gut microbe circadian rhythms by the high-fat, high-sugar diet alters the production of metabolites that keep the gut healthy, such as short-chain fatty acids. This promotes an abnormal immune response in the gut, resulting in IBD.

Circadian rhythm disruption initiated by abnormal sleep habits, such as those seen in shift workers, promotes intestinal hyperpermeability, also referred to as leaky gut (20). Leaky gut enables the movement of proinflammatory bacterial endotoxins across the intestinal wall and into the systemic circulation, a process linked to metabolic, cardiovascular, and neurodegenerative diseases.

Finally, circadian rhythm disorganization caused by disrupted sleep/wake cycles may increase one’s risk of acquiring gastrointestinal infections. Alterations in the sleep/wake cycle produced by the SCN affect the host immune defense, lowering human resistance to enteric pathogens. Disordered sleep/wake cycles also affect gut microbe circadian rhythms, impairing their ability to defend your gastrointestinal tract against infection (21). This research indicates that improving sleep habits may help protect the body against gut infections.

Genetics Impact Gut–Circadian Rhythm Connection

Genetic variability in CLOCK genes, which are involved in regulation of body clocks and circadian rhythms, affects circadian rhythms. Variations in this gene may make some people more susceptible to circadian rhythm disruption and gut health issues such as dysbiosis. People with these genetic variations may need to be especially conscious of their sleep habits and gut health in order to keep their bodies functioning optimally (22, 23).

Intestinal cells and gut microbes are key regulators of our circadian rhythms. Disruptions to either our gut health or our other circadian rhythms, such as sleep/wake cycles and feeding/fasting cycles, can have significant, widespread implications for our health. Appropriate maintenance of our gut health and circadian rhythms is crucial for finely tuning our physiology from the cellular and microbial level to the whole body. By taking care of your gut and body clocks, you may very well be able to prevent or reverse chronic diseases associated with circadian rhythm disruption and thus attain optimal health.

Key Takeaways

Since this was a pretty complex article, I thought I’d end by summarizing the key takeaways:

• It’s not just our own human cells that have circadian rhythms; the microbes that live in our gut have them too
• Things that affect our gut health—like diet, antibiotics, probiotics, and prebiotics—may also affect our sleep, hormones, immune system, and metabolism via circadian rhythms
• On the other hand, things that affect our circadian rhythms—like abnormal sleep patterns, artificial light, shift work, etc.—may affect our gut health
• Taking care of your gut will help your circadian rhythms, and vice versa