Diving into the Bile Acid Pool: The Intersection of Gallbladder Health and Microbiome Health

Alicia Galvin, MEd, RD

We all know the importance of our liver and supporting liver health. It is a critical organ that provides many functions- detoxification, bile production, glucose homeostasis, etc. But one organ that does not always get the attention it deserves is our gallbladder. Yet the health of our gallbladder can directly impact the health of our microbiome.

 

The Problem:

In 2019, gallstone disease contributed to 2.2 million ambulatory care visits, 1.1 million ER visits and 615,000 hospital discharges. In 2018, gallstone disease was the 10th most common digestive disease in ERs and the 5th most common digestive disease in US hospitals. About 15% of the US population have gallstones, which translates to about 50million people, and cholecystectomies are the 9th most common surgery in the US, to the tune of about $28,000 per procedure on average.

 

Risk Factors for Gallbladder Disease:

So what can lead to the development of gallbladder disease and gallstone progression? Here are some risk factors:

• Hypothyroidism: thyroid hormones play a role in the contraction and motility of the gallbladder, bile flow, and plays a role in regulating liver cholesterol metabolism and ultimately bile composition.

• Diabetes: High insulin levels accelerate the rate of cholesterol synthesis in the liver, which promotes cholesterol supersaturation of the bile and also slows gallbladder contraction.

• Obesity: Being overweight increases cholesterol secretion into the bile, which can lead to gallstones

• Losing weight too quickly: As the body metabolizes fat, it causes the liver to secrete extra cholesterol into bile, leading to gallstones

• Using birth control or hormone replacement: While necessary in some cases, estrogen increases cholesterol secretion into the gallbladder (supersaturates the bile) while progestins and progesterone decrease gallbladder emptying and contraction 

• Being sedentary: Exercise helps bring cholesterol into the liver to “clear” it from the circulation, and exercise increases bile acids to help solubilize the cholesterol

• Diet risk factors: fast food, high saturated fat/meat diets, refined carbohydrates, low vitamin C intake, prolonged fasting, and very low calorie diets all can increase the risk for gallbladder disease

 

What is Bile Exactly Anyway?

Bile is the greenish-yellow fluid that out liver produces, that is then concentrated in the gallbladder. Bile is made up of several components: 

• Cholesterol: Precursor to make bile acids

• Bilirubin: A yellow pigment made from the breakdown of heme in red blood cells

• Water: 98% of bile in the liver, 89% of bile in the GB

• Bile salts: Bile acids in liver are conjugated with taurine & glycine to make bile salts in the gallbladder to help emulsify fats

• Phospholipids: Lecithin and Phosphatidylcholine

• Ions: Na+, Cl-, Ca2+, K+, bicarbonate

It is important to distinguish that bile that the liver secretes has a very different composition from the bile the gallbladder secretes. For example, liver bile has only 1.1gm/dl of bile salts, bile in the gallbladder is 6x more concentrated with 6gm/dl of bile salts. This is because the bile is concentrated in the gallbladder in preparation to be used to emulsify fats from our food as well as carry out all the functions of bile. So if we don’t have a gallbladder, then that bile can not be transformed.

 

Functions of Bile:

In addition to emulsifying fat, bile also serves several other functions in the body:

• Elimination route for toxins, hormones, bilirubin, and cholesterol from the body

• Emulsifies fats and facilitates absorption

• Protects against intestinal infections by excreting IgA and stimulating the innate immune system in the intestine

• Delivers Vitamin D from the liver to the intestine, as well as B12, folate, and B6

• Regulates triglycerides, glucose and energy metabolism

 

Signs You May Have an Issue with Gallbladder Health:

Your body is able to communicate when gallbladder health may be compromised. Some warning signs could include:

• Difficulty digesting fatty meals/foods or feeling nauseated after these meals

• Light/tan stool that smells bad

• Less than 1 BM daily

• Bitter or sour taste in mouth after eating

• Nausea and vomiting

• Diarrhea

• Itchy skin

• Water retention in legs and ankles

• Gas and bloating, reflux

• Lack of appetite

• Dry skin/hair

• Feeling fullness w/ deferred pain to head, stomach and right shoulder blade

• Dark urine

• High cholesterol and/or triglycerides

 

Bile Acids as Metabolic Signalers:

Once bile has been made in the liver from cholesterol, stored in the gallbladder and released into the small intestine, they can also serve as signaling molecules for a variety of activities mediated through the farnesoid X receptor (FXR) and the G protein-coupled membrane receptor 5 (TGR5). These receptors mediate the signaling cascade and activate expression of genes involved in the metabolism of bile acids, fats, and carbohydrates, energy expenditure and inflammation in intestinal and liver tissues and peripheral organs. This means they play a role in glucose and insulin homeostasis as well.

 

Bile and the Gut Microbiome:

Bile acids have antimicrobial activity that can inhibit bacterial overgrowth and can also regulate the overgrowth and composition of the intestinal microbiota through FXR and TGR-5 to protect the liver and intestine against inflammation. But the amount of bile released into the intestine can alter gut colonization: Low levels of bile salts favors proliferation of Gram-negative bacteria (including pathogens), which contain inflammatory lipopolysaccharides as part of their cell membranes. High levels of bile salts favors the proliferation of Gram-positive bacteria. Bile salts have also been shown to inhibit Salmonella enterica pathogenicity, control pathogenesis of Clostridium difficile, and decreases E. coli O157:H7 pathogenicity.

Further, those with gallbladder disease tend to have reduced microbial diversity, a decrease in the beneficial genus Roseburia, and an overgrowth of bacteria of the Proteobacteria type, including a wide range of pathogenic microorganisms, such as Escherichia, Salmonella, Vibrio, and Helicobacter.

If the gallbladder is removed due to gallbladder disease, this can further lead to a significant change in the composition of the gut microbiota. Post-cholecystectomy there is an even more pronounced decrease in the number of taxa compared with individuals without gallstone disease and a decrease in the amount of Bacteroides, which could be a reason for the increase in the incidence of colorectal cancer in patients with cholecystectomy.

What Can You Do to Support a Healthy Gallbladder and Bile Flow?

• Take 1.5-2g high quality omega 3 fats daily as this decreases the cholesterol supersaturation

• Take ginger and artichoke extracts: Promotes gallbladder contraction, and motility- although avoid with active/symptomatic gallstones

• Take 2g Vitamin C daily in divided doses, since Vitamin C is required for the conversion of cholesterol to bile salts

• Eat fiber: 30-40g/day and make sure bowels are regular & promote bacterial diversity

• Avoid: refined sugar, simple carbs, fried foods, trans fats, refined vegetable oils, and yo-yo dieting

• Eat: healthy fats (avocado and olive oils), nuts, seeds, cholagogues (radishes, turnip greens, artichokes, beets, and dandelion)

• Exercise for at least 30min 5x a week