The Little-Known Connection between Leaky Gut, Gluten Intolerance, and Gallbladder Problems

on May 10, 2017 by Chris Kresser

Do you have patients who have trouble digesting fatty foods? Back pain or nausea? A sluggish gallbladder may be to blame. Recent evidence suggests that inflammation in the gut is closely related to gallbladder function. Read on to learn about the gut–biliary connection, how gluten might be involved, and how to get things flowing again.

As Hippocrates once said: “All disease begins in the gut.” Researchers have indeed found that many diseases are linked to changes in gut microbes or gut function. I’ve written many articles on connections between the gut and other organs on my blog:

While I have helped many patients resolve gallbladder and other biliary conditions in my clinic, I haven’t covered gallbladder issues on the blog before. In this article, I’ll discuss what the biliary system does, how it relates to the gut and inflammation, and the functional medicine approach to treatment.

The function of the biliary tract

The biliary tract, or biliary system, refers to the liver, gallbladder, and bile ducts, which work together to make, store, and secrete bile. After production in the liver, bile travels via the common bile duct to the gallbladder for storage. When dietary fats enter the small intestine, they are sensed by enteroendocrine cells, which release the hormone cholecystokinin. Cholecystokinin, in turn, stimulates contraction of the gallbladder and the release of bile into the small intestine (“chole” = gall, “cyst” = bladder, “kinin” = relating to contraction).

Try placing a single drop of oil in the center of a glass of water. The oil remains in one spot and doesn’t reach the edge of the glass, right? Add some dish soap, however, and the detergent encapsulates the oil, forming an emulsion and making the oil drop soluble in water. This is exactly how bile works in the small intestine. Bile is made up of 97 percent water, with the remaining 3 percent consisting of a mixture of bile acids, cholesterol, phospholipids, bilirubin, inorganic salts, and trace minerals (1). Bile acids act like a detergent, helping to emulsify lipids in food. A lipid droplet from food does not mix well with the rest of the contents of the intestinal lumen. For the droplet (oil) to be absorbed, it must first be encapsulated by bile acids (detergent) to form a micelle. This micelle is then soluble in the luminal contents (water) and is able to diffuse from the center of the lumen to the intestinal epithelium (edge of the glass) for absorption. Without bile, these lipids go undigested, resulting in fatty stools, a condition called steatorrhea. Bile is also crucial for proper absorption of the fat-soluble vitamins A, D, E, and K and cholesterol, all of which are transported to the epithelium in micelles (2).

Are gluten intolerance and gall bladder issues related?

(All too) common gallbladder diseases

Gallbladder disease symptoms can be steady or occur in acute episodes. Though symptoms will vary slightly depending on the exact disease, pain is usually located in the upper abdomen and may be accompanied by features such as jaundice ( a yellowing of the skin), nocturnal onset, nausea, vomiting, and radiation of pain through to the back (3). The most common gallbladder diseases are:

Cholestasis: the backup of bile flow in the liver or in the biliary ducts.

Gallstones: stones formed in the gallbladder from the components of bile. About 20 to 25 million Americans (10 to 15 percent of the adult population) are affected by gallstones (4). Gallstone disease is the leading cause for hospital admissions related to GI problems, yet over 80 percent of individuals with gallstones never experience biliary pain or more serious complications (5).

Cholecystitis: a complication of prolonged cholestasis and gallstone disease characterized by inflammation of the gallbladder tissue due to cholestasis and lack of blood flow. About 6 to 11 percent of patients with gallstones develop cholecystitis (6).

Cholangitis: a serious infection of the bile ducts that sometimes occurs as a complication of cholestasis or gallstones when the flow of bile is blocked. The infection can also spread to the liver, so quick diagnosis and treatment is very important (7).

Gallstone pancreatitis: in rare cases, a blockage of the pancreatic bile duct by a gallstone can cause inflammation of the pancreas. This occurs at the sphincter of Oddi, a small round muscle located where the bile duct opens into the small intestine (8). Like cholangitis, this is a dangerous condition and prompt treatment is crucial.

Risk factors for gallbladder disease

Those who are overweight, female, and over the age of 40 have an increased risk of gallbladder disease. In fact, females are almost twice as likely to develop gallstones (9), and 25 percent of those who are morbidly obese have gallstones (10). Underlying diseases such as inflammatory bowel disease, liver disease, and cystic fibrosis can contribute to gallbladder disease, as well as a number of prescription medications (11, 12, 13). Pregnancy, oral contraceptives, and antibiotic use have all been associated with the onset of cholestasis (14, 15, 16, 17).

Lifestyle factors also play a role. Reduced physical activity is associated with a higher risk for gallbladder surgery (18, 19). Gallstones have also been associated with a Western-type diet high in processed foods and sugar (20, 21). In a later section, we’ll also look at the role that gluten might play in gallbladder disease.

Leaky gut affects the biliary system

When intestinal barrier function is compromised (“leaky gut”), gut bacteria that are normally confined to the intestinal lumen can cross the gut barrier and enter the bloodstream. The immune system sees these microbes and their microbial products as foreign invaders and quickly launches an immune response. This can affect the biliary system, as the resulting inflammatory signaling from such a microbial invasion has been shown to alter the gene expression and function of key transport systems involved in bile uptake and secretion in the liver (22).

The connection between microbes and biliary function has been known since as early as 1901. In his classic textbook, The Principles and Practice of Medicine, Sir William Osler reports that pneumonia can lead to jaundice:

“In this form there is no obstruction in the bile-passages, but the jaundice is associated with toxic states of the blood, dependent upon various poisons which either act directly on the blood itself, or in some cases on the liver-cells as well” (23).

We now know that these “toxic states of the blood” are due to the presence of microbes in the bloodstream (sepsis) and that the “various poisons” Osler describes are inflammatory signaling molecules called cytokines, which affect transporters on liver cells.

The takeaway:

  • healthy gut → microbes remain in the colon → proper gallbladder function
  • leaky gut → microbes leak into the blood → gallbladder dysfunction and disease

Bile helps maintain gut barrier function

Like many interorgan networks, the gut–biliary connection is a two-way street. As we covered in the previous section, leaky gut and microbes entering the blood can lead to gallbladder disease and a backup of bile. But a lack of bile entering the intestine can itself cause leaky gut and an alteration in gut bacteria.

How do we know this? Researchers found that when they induced acute liver injury in animals, the animals rapidly showed evidence of increased intestinal permeability. Notably, these changes in the gut barrier preceded any changes in the gut microbiome (24). Another research group using a mouse model of cholestasis found that stimulating certain receptors in the gut with bile acids resulted in less gut inflammation and improved gut barrier function (25). This may occur by stimulating host production of antimicrobial properties at the intestinal barrier (26).

The takeaway:

  • healthy gallbladder → bile acids reduce inflammation → proper gut barrier function
  • gallbladder disease → less bile entering the small intestine → leaky gut and dysbiosis

The gluten connection: leaky gut, leaky bile duct?

I’ve written before about how gliadin, a protein in gluten, can increase the production of zonulin, a toxin that breaks down the tight junctions between epithelial cells in the gut. This causes gaps between intestinal epithelial cells and allows microbes and dietary proteins from the gut lumen to “leak” into the bloodstream (27). Hepatocytes (liver cells) and cholangiocytes (the cells that line the bile duct) are also connected by tight junctions, forming a selectively permeable barrier between the blood and the biliary system (28). Research has shown that zonulin is associated with the tight junctions in virtually all mammalian epithelia (29). In other words, if gliadin compromises the intestinal barrier and gets into the bloodstream, it can also wreak havoc on other epithelial barriers, including the blood–biliary barrier.

Sure enough, research has linked gluten intolerance and celiac disease to increased prevalence of gallstones and biliary cirrhosis (30, 31). There is also a high prevalence of celiac disease in patients with autoimmune hepatitis (32). One study found that 42 percent of adults with celiac disease had abnormal levels of liver enzymes. Adherence to a gluten-free diet for one to 10 years normalized liver enzyme levels in 95 percent of these patients (33).

Intestinal villi, the fingerlike projections on epithelial cells responsible for nutrient absorption in the small intestine, are typically shortened and damaged in celiac disease. This may impair the sensing of incoming dietary fatty acids by enteroendocrine cells, resulting in reduced release of cholecystokinin and insufficient contraction of the gallbladder (34). Studies have shown that this too can be reversed with a gluten-free diet (35).

Cholecystectomy

Cholecystectomy, the complete removal of the gallbladder, may be unavoidable in some people with late-stage gallbladder disease. In this procedure, the biliary tract is rerouted, such that bile flows directly from the liver to the small intestine via the common bile duct.

Gallbladder removal should be avoided whenever possible, as it has several unintended consequences and significantly alters physiology. Even in the absence of the gallbladder, the liver continues to produce bile. Without a storage organ, intrahepatic cholestasis, the accumulation of bile in the liver, may occur. Altered bile secretion into the small intestine has also been shown to affect gut microbes and gut function (36).

Additionally, even if a patient has undergone cholecystectomy, he or she may still continue to produce gallstones in the liver or bile ducts if the underlying pathophysiology has not been addressed (37). In the final section, we’ll discuss how to treat these conditions and restore gallbladder health.

Treating gallbladder disease: the functional way

I usually have to convince people that a functional approach is better, but in this case, there really is no conventional treatment available for gallbladder disease other than invasive surgery. Conventional medicine usually just advocates a low-fat diet. While this may alleviate symptoms over the short term, long-term reduction of fat intake only prevents the stimulation of gallbladder contraction by cholecystokinin. This can lead to more sluggishness and an increased risk of gallstones, which is what we are trying to avoid in the first place. In contrast, a high-fat diet has been shown to protect against gallstone formation, especially during weight loss (38).

On the other extreme, many natural health websites are promoting gallbladder flushes. I typically like to look to the scientific evidence to support my treatment recommendations, and as these flushes have yet to be tested in clinical trials, I think it’s better to focus on addressing the underlying causes.

That said, here are my recommendations for approaching a gallstone issue:

Test: markers of impaired gallbladder function include high ALT, AST, bilirubin, LDH, GGT, ALP, and 5ʹ-nucleotidase. Relative levels of these markers can also help narrow down which gallbladder disease you are dealing with.

Change the diet: I’ve seen many people resolve their gallbladder issues simply by changing their dietary habits. Removing inflammatory foods like gluten, processed foods, and sugar can substantially improve gallbladder health.

Heal the gut: while it’s a bit of a chicken-or-the-egg situation as to which came first, leaky gut and biliary disease certainly go hand in hand. It’s important to address both simultaneously in order to break the cycle of gut inflammation → biliary stasis → lack of bile → more gut inflammation.

Stimulate bile flow: bitters like curcumin, dandelion, milk thistle, and ginger are well known for their ability to stimulate bile flow (39, 40). These can be taken as supplements, included in meals, or consumed as tea.

Dissolve gallstones: beet root, taurine, phosphatidylcholine, lemon, peppermint, and vitamin C have all been shown to reduce the impact of or even dissolve gallstones (41, 42, 43).

Consider supplementing with bile: if your patient is having trouble with fat digestion, you can also consider having them supplement with bile itself from a bovine or ox source until his or her bile flow is restored.

That’s all for now! Did you know about the connection between the gut, gluten, and biliary disease? Let us know what you think in the comments!

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  1. What is your recommendation for those who have had their Gallbladders removed?
    Diet, (liver takes over for gallbladder??), de-tox etc etc
    Mega thanks

    I love your work, your way of presenting, your support and the depth in all you share through the Kresser Institute !

  2. Chris,

    Thanks for the article. I was wondering if you could comment on another disease that is related to bile acid and that is an excess of bile acid that enters the large intestine. I have a relative that had part of her terminal ileum removed due to Crohn’s disease and has had issues with diarrhea ever since. She was recently diagnosed with an excess of bile in her stool through the use of a stool test. She has since gone on to take cholestyramine which has had a positive impact on her diarrhea. I read that some Dr.s think that excess bile acid is a much larger problem in the general population than is currently recognized and that many cases of IBS may be related to this. Some of the questions that I have around this problem have to do with the use of cholestyramine and it impact on health and digestion. Should she avoid fatty foods, to reduce the amount of bile that enters her colon? What about meat protein (she follows a very strict paleo diet with no refined sugar or grains)? Are there other more functional approaches to dealing with this condition? She currently has some scarring and inflammation in the ileum. If she was to reduce the inflammation, might she see a more normal return to bile acid uptake? Thanks again for the info. I look forward to your thoughts and insights into excess bile acid.

  3. Thank you for this great information on Gallbladder disease. It is hard to find information for clients who have had their gallbladder removed. Do you have a recommended protocol for these clients? Many I see have digestive issues reappear a handful of years after surgery.

    • That’s tragic! People ask why I don’t trust doctors, and it’s because they’re so quick to cut/drug and they never check that they’re really solving the problem. They just turn you lose again and call it done.

    • Hi Margie,
      I have had my gallbladder removed almost 20 years ago and I would be very interested in any current information on the subject.
      Thank you for your help in this matter.
      Christine

    • Thank you for asking this, Margie. I wondered the same thing! I am aware of some who have problems with loose stools but more often, those who have difficulty with constipation. Addressing both ends of the spectrum would be appreciated!

  4. This was refreshing to read because it’s exactly what I’ve been dealing with for the last year. Started with stomach pain and gall bladder issues. Sludge in my gall bladder but no stones. Now o have an enlarged bike duct. My functional medicine doctor tells me to not get my gall bladder removed but after a year of being 99% gluten free, consuming no sugar, just mostly lean meats and veggies, and still having Issues (no more improvement since the first month off theses foods) it’s hard to stay on course and not want to get my gall bladder removed. I’ve done 2 food sensitivity panels (by well knowns labs) and all show no sensitivity to dairy or gluten but those foods definitely cause me lots of issues, along with any fermented foods. Wondering how long it takes to heal the gut? How long should one except to have symptoms continue for before they typically sees signs that things are getting better?

    • Dear Codi,
      I wanted to address your question about how long it takes to heal the gut. I, too, was amazed and discouraged by my own situation. I adhered to the diet, eliminating so many foods for months on end, eating extremely well, but no luck. I am happy to report that after three years of intensive effort, I think I have turned quite a significant corner. I actually believe I healed!! My bowels are normal, I’ve had a reduction in joint pain (I didn’t have a gall bladder issue) but it involved persistence and a lot of experimentation, trial and error, and ongoing research. I’d say to hang in there, keep trying things, get all the help you can. It will heal.

  5. My father got pancteatitis due to overlooked gallstones. The pancreatitis caused cancer and he passed away. My sister had her gallbladder removed.
    I’m pretty much sure that it’s a gluten related issue and I handle it very bad.
    There’s no doubt to me that you are absolutely right!
    Fortunately I turned into paleo for a while and I’m taking care of my gut.

  6. After the birth of my baby last year, I quickly developed cholecystitis and my gallbladder was removed, 12 weeks after giving birth. I often wonder if this could’ve been avoided but the situation was chronic and I was trying to nurse my baby too! Anyway I can’t undo what happened. I am taking milk thistle and vitamin C and am eating lots of organic cruciferous vegetables. I am taking a digestive enzyme but not one with ox bile. I would like to know more on diet and supplement choices for someone without a gallbladder.

  7. Finally, an article that explains gallbladder disease really well!! It makes so much sense. I have gallstones. When you say “Heal the gut” do you also advocate taking a probiotic? If so, which ones seem to be better for those with gallbladder issues? What wouldnone want to look for in a probiotic to also help heal the gut?
    Love your articles. Keep them coming. Thank you!!!

  8. Thanks for the article. I recently read it and a bunch of other ones on the gallbladder and issues related to it. I lost the ability to digest fats temporarily and have only slowly been getting it back by carefully and slowly increasing the amount of fat I eat each day. In addition b4 that I lost the ability to digest most proteins….and then…..candida….I mean really? WTF? (I keep a food journal–I avoid foods I find that I react to already.)

    I then went on a research binge.

    For what it’s worth this is what I treated myself with in order to restore my ability to digest fats better, and it seems to be helping me. It looks like I might restore my ability to digest fats again fully, and the increase in bile acids may help heal my leaky gut; and the healed lining of my intestine hopefully, (fingers crossed), will tell my body to produce enough stomach acid so that I can digest more protein….maybe. I hope so.

    10-12 g of vitamin C/day spread throughout the day. So that I take two g every 2 hours until I have finished. This keeps a more even and consistent amount of vitamin C in the bloodstream. Scientific testing has found that this is safe for the vast majority of adults. Some people need to start out with 2 g a day and work up to 10 g slowly in order to avoid getting the actually quite rare side effect of diarrhea.)

    Don’t take if you are one of those few people allergic or intolerant to vitamin C!!

    milk thistle 250 mg-500 mg about 20-30 min after lunch and dinner.

    Glutamine within a couple of hours after dinner and then milk thistle about 2 hours later.

    I have gone from having twinges of pain in my liver and pancreas before and after most meals to having only twinges occasionally a couple of hours after my evening meal which I think are related to one or more stones moving (hopefully moving out of a duct and into the intestine) due to the treatment.

    Most importantly to me I have found I am able to digest more fats at a time per meal now. Which is very important as my body is reactive to most proteins and I have to limit carbs because of candida….ok….I have to eat something with calories. I’m going for the healthy fats…and cheating with the candida diet on the starchy vegetables.

  9. cases people have to have their gallbladder removed, emergency situations, I have know alot of people who don’t have a gallbladder and are living, the gallbladder is a holding tank , then it goes into the liver, then from the liver it goes into your intestines, Remember it is a holding tank. But if you do still have your gallbladder diet does seem to play an important in keeping it.

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