The gut is under heavy circadian regulation, and circadian disruption can cause a number of problems when it comes to gut function. Fortunately, many of these issues can be corrected through modifying your behavior.
Whether you’re talking about SIBO, IBS, IBD, gastroparesis, or any of the number of functional gut disorders out there, a lot of benefit can be gained by doing things that optimize your circadian rhythms. For people with mild issues, one can tinker with modifying light exposure and time-restricted eating. But for those with bigger problems and a number of food sensitivities, more effort is needed.
Just how does optimizing circadian rhythms help with the gut? Well, here are 10 ways that optimizing circadian rhythms can improve gut function.
1)Increasing salivary enzyme and IgA secretion
The first step in the digestive process begins with chewing in the mouth. In addition to mechanically breaking food down, chewing seems to set the stage for digestion throughout the gut. Chewing enhances blood flow and oxygen consumption in the gut, and also stimulates the production of saliva.
Saliva contains some important substances that digest food and kill bacteria that may be in our food. This is done by salivary enzymes and IgA, respectively. Both are under circadian control and are altered under circadian disruption. How so?
Salivary enzyme secretion is altered under constant light in mice, and this caused a decrease in enzyme secretion during their subjective day, when they eat most of their food. In humans, salivary IgA peaks overnight as a way to kill any remaining bacteria in the mouth and prevent overgrowth that could lead to periodontitis.
This is pretty interesting given that the oral commensal/pathogen Candida albicans is the most common fungal infection in humans,. A recent study showed that good oral care can reduce a person’s exposure to it.
2)Coordinating gastric acid and mucus secretion
Gastric acid secretion and the replenishment of the gastric mucus layer are both under circadian control. This regulation is under control of the circadian hormones gastrin and ghrelin. Interestingly, ghrelin is secreted during periods of fasting to stimulate motivation and arousal to find food.
In the stomach, ghrelin seems to stimulate acid secretion and helps build up the mucus layer during fasting. This is important because gastric acid can damage the cells in the stomach and cause ulcers, so a thick mucus layer can prevent this from happening. It also helps prevent pathogens from making it much past the stomach intact, and from damaging the stomach lining.
3)Replenishing the intestinal mucus layer
The mucus layer in the gut plays many roles including lubricant, protection from bacteria and enzymes, and site for enzymatic breakdown of your food. Many people are aware of the first 2, but not the second 2. The digestive enzymes that we make can actually destroy our gut wall, save for the brush border enzymes that perform the final breakdown of carbohydrates.
Fat and protein digesting enzymes from the saliva, stomach, and pancreas could tear our gut to shreds. So having a barrier between the cells lining the gut and these enzymes is crucial to maintaining a healthy gut. However, the mucus layer also helps our digestive enzymes by giving them longer contact time with the food we eat. This helps optimize digestion while at the same time saving the cells of the intestinal wall from damage due to friction, bacteria, or immune activation.
4)Modifying the microbiome
The microbiome has become a hot topic in health over the last 10 years. This led to the belief that, in short order, we’d be able to figure out what an ideal microbiome is and recapitulate it with probiotics or fecal microbiota transplants. Then came the last couple of years and that all went up in smoke.
It turns out that the microbiome has its own circadian rhythm, with different bacterial species increasing/decreasing in number and closeness to the gut wall throughout the day. Not only does this have an effect on our circadian rhythm, but the circadian rhythm of the microbiome appears to be regulated by…wait for it…our circadian rhythms.
This makes sense, the nutrients that the microbiome has access to is directly affected by when and what we eat. When we eat we see an increase in the abundance of bacteria that snack on carbohydrates, and when we fast we see an increase in bacteria that snack on our mucus layer. This allows us to replace the mucus layer daily to prevent bacterial overgrowth, particularly in the small intestine.
But it turns out it’s not simply just when and what we eat. Aberrant light/dark cycles change both the types of bacteria in our gut as well as their functions, leading to “leaky gut”. In fact, most of our behaviors that alter circadian rhythms will likely have an effect on the microbiome and vice versa Successfully using probiotics or FMT will require addressing circadian rhythms to be even remotely useful, save for addressing acute problems such as C. diff infection.
5)Repairing and replacing damaged cells
At the cellular level, circadian rhythms help separate functions that can’t go on at the same time due to conflicting metabolic processes. Nothing illustrates this concept more than the separation of use and repair. In the most basic sense, you can’t repair or replace something while it’s in use.
Anabolic(Building up) and catabolic(breaking down) processes need to be separated because they often use the same substrates. They also need to be separated because some of the byproducts of catabolic processes such as free radicals damage cellular components such as DNA, which if altered during replication, can lead to cancer.
Think of it like getting an oil change in your car. You can’t run the engine while changing your oil because removing the oil would cause the engine to seize. Therefore, you must take your car off the road to change the oil. In the same way, sending the proper signals to your cells via the correct environmental exposures will allow your cells to separate use from repair, keeping your gut healthy all day every day.
6)Preventing leaky gut
“Leaky gut” has become quite a frequently searched term on google. But, every one of us experiences it every day. The permeability of our gut waxes and wanes throughout the day due to circadian rhythms and there’s no real way around this. Eating is an inherently inflammatory event, and the gut needs some downtime every day to replace damaged cells. Thus, if you put food down there at the wrong time, you’re going to cause some real damage.
But it’s not as simple as, “Don’t eat at night”. Replacing damaged cells isn’t the only circadian factor that plays a role in “leaky gut”. Hyperglycemia can cause it, as can the overgrowth of both pathogens and commensal bacteria from the microbiome. Additionally, secreted factors from basically every tissue throughout the body can play a role in making sure your gut stays sealed and bacteria stay out of your bloodstream. The specifics of these factors will be discussed briefly below.
7)Improving bile output
When we think of bile output, most people only think of the emulsification and absorption of fat and fat soluble vitamins. But bile also plays a role in mucosal defense through its direct antimicrobial action and secretion of antimicrobial peptides, promotion of the housekeeping phase of the gut known as the migrating motor complex(MMC), and increased expression of tight junction proteins to seal up the gut.
But bile can also cause injury to the gut, and circadian disruption can change the composition of bile making it more damaging. This is likely due to changes in both the types of bile acids synthesized in the liver as well as the bacterial species in the gut that convert primary bile acids in to toxic secondary bile acids.
8)Strengthening mucosal defense
The gut is constantly exposed to bacteria and other microorganisms that can cause damage to it and us. Lucky for us there’s a system in place inside the gut to prevent that from happening called the mucosal defense system, which is under circadian regulation. Mucosal defense is an umbrella term used to describe the various ways the gut prevents damage to it and us.
I’ve already mentioned a few of the ways the gut protects us such as mucus secretion, enzyme secretion, barrier integrity, and bile output. But another important mechanism of mucosal defense is the secretion of antimicrobial peptides. Secreted by Paneth cells, antimicrobial peptides kill bacteria, particularly in the ileum where components from bile trigger their release.
This location is key as it’s at the border of the small and large intestine, where bacterial numbers move from very low to their highest. If even healthy bacteria overgrow in to the ileum, we get an increase inflammation and increased translocation of bacteria in to the blood.
9)Correcting dysregulated motility
Proper motility throughout all areas of the gut is crucial to proper digestion and preventing bacteria from overgrowing in areas they shouldn’t grow. It’s also important for the consistency of your stool. Motility in all areas of the gut is under circadian regulation.
In the small intestine, motility is greatest during the day and lowest at night. It’s not surprising, then, that people who eat at night are at an increased risk for functional gut disorders such as SIBO, IBS, and IBD. For most people, their greatest period of fasting is during the night. The problem is that the migrating motor complex(MMC), which cleans house to prevent bacterial overgrowth, functions poorly at night, particularly during sleep.
Motility in the colon is also lower at night, and affected by meal timing. Generally, colonic motility is greatest during the morning and after meals. When disrupted, this can cause low colonic motility which leads to constipation or rapid colonic motility which leads to diarrhea. Meal size and substances such as coffee also affect colonic motility, so timing these things incorrectly can lead to problems in stool consistency.
What goes on in the gut isn’t solely dictated by things in the gut. Just like the microbiome communicates with us, other organs and tissues throughout our body communicate with each other to optimize function. In my opinion, ignoring this fact is probably one of the biggest factors preventing people from overcoming functional gut disorders.
When we zoom away from the hyperfocus on the avoidance of foods most people have in curing gut problems, we can get a pretty good picture of how expansive the interaction is between our gut and the rest of the body.
- Cortisol, secreted from the adrenal glands in a circadian manner, promotes the recycling of bile acids and functions as a systemic anti-inflammatory.
- Irisin, a myokine secreted from exercising muscles, also functions as a systemic anti-inflammatory and promotes the healthy remodeling of the lymphatic system in the gut.
- Insulin, secreted by the pancreas to prevent hyperglycemia, also plays a role in preventing hyperglycemia-induced leaky gut and inflammation.
- Many different adipokines, signaling molecules secreted from fat cells, can increase inflammation in the gut. Particularly when secreted from a fatty liver or the creeping fat surrounding the intestine in people with Crohn’s disease.
These are just few of the different local signaling molecules released from distant tissues that can have an impact on inflammation in the gut.
As I’ve mentioned numerous times, the gut is under heavy circadian regulation. To ignore this critical aspect of gut health is probably one of the biggest factors leading to a gradual increase in the number of foods people with gut disorders become sensitive to. As a result, pulling more and more foods out of our diet and ignoring circadian rhythms leads to a very short list of foods people eat that can lead to nutritional deficiencies.
In my experience, addressing circadian rhythms is the most bang-for-your-buck therapeutic approach to fixing sensitivities to foods and optimizing gut function. When we look at the many functions in the gut regulated by circadian rhythms and how they impact food sensitivities, a pretty clear picture emerges.
Without adequate enzyme secretion and a thick mucus layer, we get undigested food that can interact with our gut lining or feed a bacterial overgrowth. With poor motility and inadequate antimicrobial peptide secretion we promote an environment conducive to bacterial overgrowth. Finally, with poor cell turnover and tight junction expression, we end up with a damaged leaky gut that leads to system-wide inflammation, metabolic dysfunction, and an even leakier gut.