IN THIS ARTICLE:
Chronic illnesses such as Lyme disease and mold illness are often accompanied by decrements in the body’s natural detoxification capabilities. In such illnesses, the continual circulation of toxins and inflammatory signaling molecules overwhelms our innate detox pathways, creating a vicious cycle of toxicity and illness. Bile is a digestive fluid that plays a critical role in facilitating the excretion of toxins from your body and in maintaining a healthy gut microbial balance. Read on to learn how foods and nutrients can be used to support bile flow, enhancing your detoxification pathways and gut health.
In This Article:
The Connection Between Bile Acid Receptors, Detox, and Gut Health
Detoxification is a complex, multi-step process in which toxins are moved out of cells, through the liver and gallbladder, and out of the body through the intestines and kidneys. Many popular detox kits and products focus on supporting the liver or kidneys, but the role of the gallbladder and its secretion, bile, is rarely addressed.
Bile is a fluid produced in the liver and released by the gallbladder that solubilizes dietary fats, thereby enhancing fat and fat-soluble vitamin absorption. However, it also serves as a stimulus and vehicle for excreting toxins from the body. Bile is comprised of bile acids (also referred to as bile salts), cholesterol, phospholipids, and water. Intriguing research indicates that the cellular transporters that carry bile acids in and out of the intestine also transport toxins, including heavy metals, mycotoxins, and bacterial toxins! (1, 2, 3) Gut dysbiosis impairs the activity of bile acid transporters, reducing the elimination of these toxins and perpetuating (and possibly worsening) overall bodily toxicity. Supporting healthy bile flow is thus essential for gut health, detoxification, and reducing your toxic burden.
An Overview of Bile Acid Receptors
Before I dive into a discussion of foods and nutrient-based ligands for bile acid receptors, I want to provide a brief overview of some of the receptors involved in bile acid and toxin transport between cells, the liver and gallbladder, and the gut.
FXRα: Farnesoid X receptor alpha is a nuclear receptor that plays a role in the transcriptional control of bile acid transport and metabolism. It prevents the accumulation of toxic byproducts derived from endogenous metabolites and exogenous toxins within cells. (4)
PXR: Pregnane X receptor is a nuclear receptor that works in conjunction with FXRα to regulate xenobiotic (exogenous chemical substances) metabolism. (5)
CAR: Constitutive androstane receptor is another nuclear receptor that works in conjunction with FXRα and PXR. It plays a role in the activation of bile acid synthesis and is a metabolic sensor that activates proteins that enhances the metabolism and excretion of xenobiotics. As you can see in the diagram below, it is concentrated in the liver.
OATP: Organic-anion-transporting polypeptide is a membrane transport protein that acts as a “gatekeeper” for the cell. It transports xenobiotics between the liver and intestine through the portal blood supply.
BSEP: Bile salt export pump mediates the excretion of bile salts (bile acids) through bile ducts into the intestine. It’s function is impaired by endotoxin/LPS. (6)
MRP: Multidrug resistance protein is a member of the ATP-binding cassette (ABCs) family of proteins. ABCs transport a variety of molecules across intracellular and extracellular membranes, including heavy metals. (7) It is downregulated by LPS. (8) Activation of these proteins protects cells from the damaging effects of Fusarium mycotoxins; however, at high enough levels, mycotoxins interfere with the activities of these proteins. (9) This is one reason why it is so important that people with mold illness consume foods that upregulate their MRP proteins (and other bile acid receptors).
The movement of toxins out of cells via bile acid receptors, into the liver and bile, and out of the body through the intestine is referred to as “Phase III detoxification.” Phase I involves the reduction or hydrolysis of a toxin, creating a more reactive intermediate. It is usually performed by CYP450 enzymes. Phase II detoxification involves conjugation of the reactive intermediates using compounds such as glutathione conjugation and methylation. Essentially, Phase III detox finishes up the process, ushering conjugated toxins out of the body.
The biochemical processes of bile acid synthesis and transport are complex and intertwined with toxin metabolism and excretion. Diagram is courtesy of Garcia M, et al. Int J Mol Sci. 2018; 19(11): pii: E3630.
Bile Acid Receptors and Mold Illness
In mold illness, normal physiological functions of the body become impaired due to exposure to biotoxins, including mycotoxins. It turns out that mycotoxins are transported in and out of cells, bile, and the intestine via bile acid receptors.
OAT 1, 2, 3, and 4 transport ochratoxin, a group of mycotoxins produced by Penicillium verrucosum and Aspergillus molds. (10) Ochratoxin is a frequent contaminant in water-damaged houses, heating ducts, and in coffee, cocoa, wine, beer, dried fruits, and the meat of ruminant animals fed mycotoxin-containing grains.
The mycotoxin patulin increases expression of PXR (pregnane X receptor), a member of the nuclear receptor superfamily that is a critical regulator of bile flow and metabolic detoxification. (11)
Supporting healthy bile flow is essential for eliminating mycotoxins from your cells and gut. However, stimulation of bile flow must be followed by consumption of a binding agent such as activated charcoal to mop up the liberated mycotoxins before they can be reabsorbed via the enterohepatic circulation. The orchestration of this process can be complex, so I recommend working with a provider such as myself or another mold-literate healthcare provider to make sure your protocol is on point.
Bile Acid Receptors and SIBO
Small intestinal bacterial overgrowth (SIBO) is a notoriously difficult condition to treat. Low levels of bile may contribute to the pathogenesis of SIBO by favoring the proliferation of Gram-negative bacteria (including pathogens) and limiting the growth of beneficial gut bacteria. (12)
The relationship between bile and SIBO also works in the opposite direction – Lipopolysaccharide (LPS), a toxic bacterial byproduct that accumulates in SIBO, downregulates the activity of bile acid receptors, decreasing bile flow and increasing the body’s toxic burden.
Enhancing bile flow may help eradicate SIBO because the presence of bile in the intestine shapes a healthy gut microbiota and assists in the detoxification of LPS. (13) Of course, bile flow support should accompany dietary changes, botanical antimicrobials, and motility and gut-brain connection interventions to fully optimize the SIBO recovery process.
Foods and Phytochemicals That Activate Bile Acid Receptors
A variety of foods and phytochemicals (plant-based chemicals)stimulate bile acid receptors, enhancing bile flow and cellular detoxification of heavy metals, mycotoxins, and bacterial toxins. A key characteristic shared by these diverse foods share is their bitter flavor. Stimulation of bitter taste receptors, located not only on the tongue but throughout the gastrointestinal tract, enhances intestinal release of the hormone cholecystokinin (CCK), a principal regulator of gallbladder contraction and bile acid release. (14)
Organic Green Tea
Green tea contains an antioxidant (a flavan-3-ol, to be exact) called EGCG that promotes FXR-induced BSEP expression, assisting with cellular toxin elimination. (15) Be aware that green tea can be contaminated with mycotoxins, so try to source the cleanest organic green tea you can find. If any outstanding brands come my way, I will be sure to share them with you!
Extra virgin olive oil is a central component of several purported “gallbladder cleanses.” While I am doubtful of the efficacy of these “cleanses,” there is scientific evidence indicating that olive oil enhances bile flow. (16) In my clinical practice, I’ve found that people with sluggish gallbladder function and bile flow tend to do best with monounsaturated antioxidant-rich fats such as olive oil, compared to heavier, saturated fats such as beef fat (tallow) and butter.
Docosahexaenoic acid (DHA) is a polyunsaturated omega-3 fatty acid found in seafood and certain types of algae. It has been found to upregulate FXR-induced BSEP expression and bile salt detoxification. (17, 18)
Cruciferous vegetables (broccoli, cauliflower, kale, brussels sprouts, etc.) are rich in a compound called glucoraphanin. When these vegetables are chewed, an enzyme called myrosinase is released, which triggers the conversion of glucoraphanin into sulforaphane, a sulfurous compound that belongs to the isothiocyanate family. Sulforaphane induces FXR activity. (19)
While drinking warm lemon water may be a “trending” thing to do in the health space, there may actually be some benefit in this practice! Lemon is rich in a compound called limonene, which may be an effective agent for dissolving gallstones, thereby improving bile flow. (20)
Bitter herbs such as dandelion, gentian, and myrrh (referred to as guggul in in Ayurvedic medicine) have been used for centuries (possibly longer, in the case of myrrh) for stimulating bile flow. It turns out that these botanicals contain phytochemicals that activate BSEP, MRP, and other bile acid receptors. My favorite herbal bitters supplements are made by Quicksilver Scientific; their Bitters No. 9 is best for gentle detoxification in highly-sensitive individuals, and their BitterX product is ideal for those in need of stronger detoxification support. Disclaimer: I do work for Quicksilver Scientific, the producer of these bitters products; however, I was a fan of their detox support supplements long before I became an employee!
Do you eat foods and nutrients that support your bile flow? Do you struggle with health issues related to poor bile acid receptor function and impaired bile flow? If you could use help fine-tuning your diet to enhance bile flow, detoxification, gut health, and recovery from chronic illness, check out the Clinical Nutrition Services page of my website to learn how I can help!
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