Summary: The enterohepatic circulation is a recycling loop for bile and nutrients between the liver and digestive tract that’s responsible for several important functions. These functions include microbial defense, maintaining intestinal barrier integrity, setting the microbiome, optimizing detoxification, inhibiting inflammation, promoting fat and fat soluble nutrient uptake, and the regulation of glucose and lipid homeostasis throughout the body. This recycling occurs 6-10 times a day and is a major factor in regulating the gastrointestinal environment. Pharmaceutical drugs as well as environmental and bacterial generated toxins also cycle through the enterohepatic circulation to promote detoxification as well as elimination toxins in the urine and feces. Defects in the enterohepatic circulation are implicated in Crohn’s disease, SIBO, fat malabsorption, and is a major cause of diarrhea in people with Irritable bowel syndrome(IBS).
You’re probably wondering what that big word above is and why you should care about it. Perhaps it’s a weather term, a constellation in the sky, or a sweet dance move ready to replace twerking or dabbing. Unfortunately for you it’s none of those things, and if you have major digestive issues or chemical sensitivities it likely contributes to your problems.
Understanding the enterohepatic circulation, what it does, and how to improve it can lead to major improvements in your digestive health. Some major IBS symptoms are the result of defects in the enterohepatic circulation. Understanding the enterohepatic circulation can shed some light on:
- How SIBO in the ileum gets started
- Why detoxification takes so long
- Why your hormones are out of balance
- Why you can go from feeling great to horrible even during periods when have not eaten
- Why you don’t absorb fat well
Over the course of this blog, I’ll try to break down this complex topic in a way that’s easy to understand. I’ll also try to provide you with practical information to improve your IBS symptoms. So let’s begin.
The enterohepatic circulation
The enterohepatic circulation is a loop involving the intestine(Entero) and the liver(hepatic). An important function of the enterohepatic circulation is to circulate fat soluble substance between the liver and intestine until they become water soluble. These substances are then removed from the body via the feces and urine. Two types of substances that go through this process are pharmaceutical drugs and toxins. In this way, the two major organs of detoxification are the liver and intestine.
One of the major components of the enterohepatic circulation is bile. Bile is important for the digestion and absorption of fat and fat soluble vitamins. The liver synthesizes bile from cholesterol and stores it in the gallbladder between meals. The liver also deposits water soluble toxins in to the bile to remove them via the feces.
The primary components of bile are bile acids, conjugated bilirubin, phospholipids and water. Bile acids can damage the gallbladder and intestine, so the liver conjugates them with glycine or taurine. This process makes them more water soluble so they don’t damage your cells and they can be removed from the body via the feces.
Once food enters the duodenum, the gallbladder contracts and forces bile in to the small intestine. Coincidentally, this is the only way to remove excess cholesterol from the body, the only other way we can lower cholesterol is by producing less of it. High cholesterol is a potential sign that bile production is insufficient.
Bile mixes with your food and makes its way through the digestive tract. Bile then emulsifies fats in the food, allowing fat digesting enzymes to do their job. Since fat doesn’t mix with water, emulsification is necessary to increase the surface area of fat exposed to digestive enzymes. The digested fats get packaged in to micelles and become absorbed. Without micelles, fat can’t enter the body. Without bile, fat can’t be rendered small enough to get packaged in to micelles.
Once the micelles and any excess bile make it to the end of the small intestine, absorption occurs. Fats enter the lymphatic system while bile salts go to the liver via the portal vein. Approximately 95% of bile salts get recycled every day. A minor amount enter the large intestine(Colon) and get sent packing out the back door.
Or that’s what you’d like to happen. Unfortunately, that’s not always how it goes. If you’ve ever experienced bile acid diarrhea, you already know this.
So what goes wrong?
So you have the basic gist of the enterohepatic circulation, but what goes awry to gum up the works? There are many factors at work here, but one of the biggest ones is the solubility of the bile and toxins. To understand this, my primer on detoxification, which you can read here, is helpful.
If you want to bale on the detox primer, here’s a basic rundown. The 3 phases of cellular detoxification make fat soluble molecules more water soluble. This allows you to remove them from the body by dumping them out via the urine or feces. Fat soluble molecules accumulate in the body because our primary method of removing things from the body requires dumping them in to the blood where they get removed via the urine, feces, and sweat. All of these substances are water based.
For the most part, the contents of the small intestine are water soluble, which is a wonderful thing. Cells lining the digestive tract separate its contents from the blood. These cells have a plasma membrane made up of lipids(aka fats) that separate the contents of the lumen from the bloodstream.
Something that’s water soluble is poorly soluble in fat and vice versa. This prevents water soluble molecules from entering cells and passing through them. Water soluble molecules can’t enter the bloodstream because they can’t pass through cell membranes. In order for a water soluble molecule to enter the blood, these cells must contain transporters to carry it across.
Most of these transporters only carry a specific molecule, which is another good thing. This makes it difficult for renegade stragglers to gain access to the blood. Most water soluble toxins stay in the intestine and make their way through the colon and out in to the feces. Any that sneak to the body can be removed easily. Bile acids get reabsorbed via transporters in the ileum and sent to the liver for recycling.
On the other hand, fat soluble molecules are problematic because they can enter cells through the plasma membrane. Fat soluble toxins that pass through a cells plasma membrane are toxic to the cell if they remain there. These toxins must enter the detoxification process or they will cause cell death. Since your intestinal wall is made up of a single layer of cells, cell death allows the contents of the intestine to enter the bloodstream.
Even bile acids are problematic. When bile acids are initially made in the liver, they are fat soluble and cell toxic. As mentioned above, they must be conjugated with either glycine or taurine or they can enter cells and cause cell death. Conjugation is one of the first phases of cellular detoxification.
This is where the bacteria in your gut enter the picture. Unfortunately, you aren’t the only one acting on bile acids and toxins. Bacteria in your digestive tract deconjugate bile acids and toxins. This makes them more fat soluble and available to damage cells of the intestinal wall. They can also pass through these cells and enter the blood. Luckily the first place they go is to the liver to re-live this entire process.
This repetitive process of detoxification/retoxification is why it takes so long to detox. It’s also why you can go through periods of feeling crummy alternated with feeling fine. The recycling of bile occurs 2-3 times for each meal. Problems caused by bile would present well after a meal, and symptoms could have an ebb and flow.
Too bad there aren’t any sentinels to ward off these evil-doers.
Bile acids-microbial defenders
Microbial defense refers to the regulation of the bacteria in your gut. Not only do you want the right type of bacteria in your gut, you don’t want too many of any kind. The primary factor that sets the stage for this is the gastrointestinal environment.
Bile acids are antimicrobial due to their action on cell membranes. Their antimicrobial effect amplifies when they bind to bile acid receptors in the ileum. This causes antimicrobial peptide secretion which impairs bacterial growth. These effects are important because the neighbor of the ileum contains trillions of bacteria. Activation of bile acid receptors in the ileum also decreases inflammation and intestinal permeability. All of these factors prevent bacteria from overgrowing in to the small intestine, aka SIBO.
As mentioned above, 95% of the bile acids bind to transporters in the ileum and get recycled to the liver. The 5% that remains enters the colon and gets converted to secondary bile acids. If excess bile acids enter the colon, they cause a rapid influx of water and diarrhea. This is bile acid diarrhea or bile acid malabsorption and is common in people with IBS-D.
Bile acid malabsorption can occur for many reasons. People with Crohn’s or Celiac disease, SIBO, or ileal resection often experience bile acid diarrhea. It isn’t clear whether SIBO is a cause or consequence of bile acid malabsorption. What is clear is that proper bile signaling is an necessary to prevent SIBO.
Estrogen and thyroid hormone got you running hot?
You may have known about the enterohepatic circulation involving bile, but there is more. It may come as a surprise to you that certain hormones take part in their own enterohepatic circulation. Excess estrogen and T4/T3 are also dumped in to the bile by the liver.
Bacteria in the gut transform these hormones where they can re-enter the circulation. This affects fertility, weight loss, energy levels and improves with dietary fiber intake(1). Coincidentally, many pharmaceutical drugs are biotransformed(aka detoxified) via the enterohepatic circulation. Fiber can also affect their processing and removal(2).
And it’s not just hormones, vitamins also take part in the enterohepatic circulation. While people search to find out if they have poor methylation genes, most aren’t even aware that folate gets recycled via the enterohepatic circulation. This means that both the liver and the intestine are primary players in the methylation cycle. A defect in the enterohepatic circulation is more detrimental to folate status than any of the polymorphisms in MTHFR, TS, or MTR. There are alternative pathways of folate methylation, but there is no back up for the enterohepatic circulation.
Environmental toxins are also recycled via the enterohepatic circulation. Toxins such as bispehol-A(BPA) and polychlorinated bipheyls(PCBs) are fat soluble molecules known as persistent organic pollutants as well as endocrine disruptors. BPA is ubiquitous in plastics while PCBs have been out of use since 1979 in the United States. Despite being banned in 1979, PCBs are still found in human blood due to their persistence in the environment and the food chain.
Due to poor biodegradation, chemicals like BPA and PCBs remain in the environment for long periods of time. When animals ingest them, they enter the enterohepatic circulation. Best case scenario, they re-enter the environment in your urine or feces. Unfortunately, they re-enter the soil, plants, and the animals that eat both.
The above is better for the health of an animal than holding the toxin in the circulation. But there is evidence that not all the toxins leave the body. Fat soluble toxins that an animal can’t detoxify get stored away in their fat cells. This includes humans(3). Here they’re relatively inert, but they get released in to the bloodstream when you burn fat(4). When an animal eats the fat of animals exposed to these environmental toxins, the torch gets passed. They enter that animals enterohepatic circulation and go through the same process.
It’s important to understand that this whole process regulates the internal environment. It’s exactly the same whether you are detoxifying an environmental toxin, metabolizing a pharmaceutical drug, or changing a hormone to make it inert or more potent. What most people call detoxification is more properly called biotransformation.
Many people know about the “detoxification” enhancing effects of blueberries, turmeric, and cruciferous vegetables. These effects are due to the body identifying a molecule in these foods as toxic. Fortunately, your body overreacts to these relatively inert molecules and your biotransformation pathways take care of actual toxins as well.
A great illustration of this process is seen with the beneficial side effects of the IBS-D drug Xifaxin. If you haven’t read it yet check it out here. It’s pretty amazing and shows why people see good results while on the drug only to see symptoms come back. Here’s a hint…It has nothing to do with the drugs antibiotic effect.
The enterohepatic circulation is a key regulator of the gastrointestinal environment. It can have a dramatic impact on the bacteria that make up the microbiome as well as the health of the intestinal wall. This cycle is altered in Crohn’s disease(5) and can be a primary cause of diarrhea due to bile acid malabsorption(6). It also modulates blood levels of hormones and ingested pharmaceutical drugs and toxins. Finally, it’s also critically important in the proper recycling of vitamins such as folate as well as vitamins B12, A & D.
The enterohepatic circulation is required for microbial defense and promotes a healthy gastrointestinal environment. This promotes the growth of commensal bacteria and inhibits pathogenic bacteria. Bile can be damaging to the intestinal wall, but other components of the enterohepatic circulation mitigate this damage.
Given that the enterohepatic circulation of bile occurs 6-10 times every day, it’s a major factor in gastrointestinal health. No other environmental factor cycles through the gut as much as the contents of bile. Not gastric acid, not pancreatic enzymes, nothing. Now you know how important it is, so what’s next?
What to do…What to do…
Now that you can see the importance of the enterohepatic circulation , you may be wondering what you can do to optimize it. There are some key nutrients that are critical to a smooth running enterohepatic circulation. Despite the involvement of these nutrients throughout the digestive process, they’re on no one’s radar. The roles that these nutrients play in the digestive process include:
- Enhancing gastric acid and enzyme secretion
- Preventing SIBO
- Healing ulcers and inhibiting H. Pylori overgrowth
- Promoting the growth of commensal bacteria while inhibiting pathogenic bacteria
- Optimizing cellular detoxification
- Inhibiting gastrointestinal inflammation
- Promoting apoptosis(programmed cell death) over necrosis(cell death due to disease)
- Increasing the integrity of the intestinal barrier
- Regulating gastrointestinal pH to optimize digestive enzyme activity
- Optimizing nutrient digestion and uptake
- And more…
We know these nutrients for their roles in other systems, but research is beginning to show their importance in digestion. These nutrients are prime targets for a few reasons. First, most people who experience digestive problems also have other issues caused by a lack of these nutrients. This would present as vision disturbances, brain fog, electrolyte imbalance and hormonal issues.
Recommended intakes for these nutrients are either non-existent or based on old data. A great example is vitamin K. Vitamin K has a reference daily intake(RDI). The RDI is based solely on preventing a defect in blood clotting. Thus, it completely ignores the many other roles of vitamin K. Most of these roles have only recently been discovered.
The final reason these nutrients are important is likely the most important. There is a heavy evolutionary or biological basis for their need in human nutrition. Even in the absence of hard evidence, the strong evolutionary importance of these nutrients and the unique ways we have been able to manipulate our food system make us stand out among our other primate and animal friends.
Our next steps are to peel back the curtain, identify these nutrients, and give a thorough rundown on what they do in the digestive process. The first nutrient on deck is super important, but not just anyone will get access to this information. Sign up for our facebook group here and we’ll give you a password to access this content.
I’m gonna publish this bad boy next week. Trust me, you don’t want to miss it, this information isn’t covered anywhere else, so sign up.
Hey peeps, please comment below and tell me if I’m able to resonate with you. Is this stuff too complex? Am I too wordy? Did you find it helpful? These are very complex subjects and I want to make it accessible to all. I personally believe topics like this are crucial to understanding digestive disorders.