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Search our catalog of clinical and scientific nutrition articles based on current clinical research studies and previously published webinars.

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Search our catalog of clinical and scientific nutrition articles based on current clinical research studies and previously published webinars.

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Search our catalog of clinical and scientific nutrition articles based on current clinical research studies and previously published webinars.
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Feb 13, 2018

Bile Acid Metabolism 101 – Why it is important to recycle less and how bile acid transformation by gut microbes can make or break our health.

Bile is an essential component of digestion.  It is basically the body’s detergent that emulsifies dietary fat, making it less hydrophobic so that we can absorb it.  In addition, it likely helps with some aspects of protein digestion as well.  The liver dumps numerous toxins into our bile, hoping that it can serve as an exit route from the body.  If bile is not bound to certain types of fiber and eliminated from the digestive tract, it can be damaging to the gut lining.  Bacteria may help us however, as they have the ability to convert bile acids to less inflammatory and even possibly protective metabolites.  With just these few aspects in mind, it is easy to see why bile and its ultimate fate-either recycled, biotransformation, or elimination-are critical.

Bile is stimulated primarily by lipid consumption.  Attempts to look at various fats (saturated vs. unsaturated) and cholesterol influences on bile secretion have not yielded distinct differences.  Some studies have actually shown that low fat, higher protein foods such as skim milk produce larger bile secretions by the gall bladder than many high fat foods (1).  Efforts to demonstrate relationships between specific dietary patterns and risk of gallstone formation have also failed repeatedly.  In fact, meta-analyses by the Cochrane Group illustrate the ineffectiveness of the currently accepted and standard protocol for gallstone/bile acid precipitate-related issues (2).  For those with gallstone obstruction of the gallbladders’ biliary duct and/or those with histories of gallstone formation, a low- fat diet is the most frequently recommended intervention.

Certain types of fiber can significantly influence our body’s bile acid pool.  This may be protective.  Most noteworthy are those fibers such as beta-D-glucan, often concentrated in root vegetables.  These fibers have a unique ability to bind bile acids and carrying them out of the body upon elimination.  This breaks what is referred to as entero-hepatic circulation.  Entero-hepatic circulation is a pathway in which substances originating in the liver are absorbed in lower regions of the digestive tract and return to the liver.  Although this a normal travel route for a major percentage of bile acids.  It is not always ideal, especially if our liver is attempting to dispose of toxins or our bile acid pool is too large for adequate biotransformation because of less than optimal populations of beneficial or commensal microbes.

The importance of the role that these bacteria play is becoming increasingly clear.  Making bile acids more or less compatible with our GI tract,  controlling processes such as inflammation and detoxification, along with reducing carcinogenicity, are clearly under microbial control (3,4).   Diseases and disease patterns such as cancer and metabolic syndrome are highly sensitive to the presence of bile acids and particular bile metabolites (5).  There is also considerable evidence to the role of specific bio-transformed bile acids, such as lithocholic acid (LCA).  LCA has demonstrated an ability to alter immune activity through vitamin D receptors on white blood cells.  A major percentage of our immune system lies in close proximity to the intestinal lining, so this relationship is profound (6).  Microbial altered bile acids in the form of LCA may provide considerable protection against obesity, cancer, autoimmunity, and cardiovascular disease.  The importance of microbial diversity within the microbiota and specific families such as Bifidobacterium and Lactobacillus species are apparent (7).  For those with dysbiosis, imbalances in gut flora, the absence of pivotal microbes responsible for biotransformation is a major risk factor for numerous metabolic disorders such as non-alcoholic fatty liver disease (NAFLD) (8).

The recent Liquid Hope animal trial at University of Pittsburgh Children’s Hospital produced significant differences among those groups of mice receiving different enteral formulas.  One of the most dramatic differences was the amount of LCA found in the fecal samples of Liquid Hope-fed mice.  These levels were markedly higher than those found in the other enteral formula-fed mice.  Again, higher LCA levels are reflective of healthy bile acid metabolism and the presence of commensal bacteria that reduce inflammation.  The organic whole food ingredients, absence of emulsifiers, organic flax seed oil, as well as the diverse vegetable fibers, create the necessary environment for these essential bacteria and the processes that they drive.

 ~ John Bagnulo MPH, PhD.

 

Resources:

1. Marciani et al. Effects of various food ingredients on gall bladder emptying. European Journal of Clinical Nutrition volume67, pages1182–1187 (2013).

2. Madden et al. Modified dietary fat intake for treatment of gallstone disease. Cochrane Database of Systematic Reviews. First published 22 March 2017 Cochrane Hepato-Billiary Group.

3. Li T, Apte U. Bile acid metabolism and signaling in cholestasis, inflammation and cancer. Advances in pharmacology (San Diego, Calif). 2015;74:263-302. doi:10.1016/bs.apha.2015.04.003.

4. Copple BL, Li T. Pharmacology of Bile Acid Receptors: Evolution of Bile Acids from Simple Detergents to Complex Signaling Molecules. Pharmacological research. 2016;104:9-21. doi:10.1016/j.phrs.2015.12.007.

5. Mališová L, Kováčová Z, Koc M, Kračmerová J, Štich V, Rossmeislová L. Ursodeoxycholic Acid but Not Tauroursodeoxycholic Acid Inhibits Proliferation and Differentiation of Human Subcutaneous Adipocytes. Huang W, ed. PLoS ONE. 2013;8(12):e82086. doi:10.1371/journal.pone.0082086.

6. Kollitz EM, Zhang G, Hawkins MB, Whitfield GK, Reif DM, Kullman SW. Evolutionary and Functional Diversification of the Vitamin D Receptor-Lithocholic Acid Partnership. Zhang C, ed. PLoS ONE. 2016;11(12):e0168278. doi:10.1371/journal.pone.0168278.

7. Ruiz L, Margolles A, Sánchez B. Bile resistance mechanisms in Lactobacillus and BifidobacteriumFrontiers in Microbiology. 2013;4:396. doi:10.3389/fmicb.2013.00396.

8. Mouzaki M, Wang AY, Bandsma R, et al. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease. Aspichueta P, ed. PLoS ONE. 2016;11(5):e0151829. doi:10.1371/journal.pone.0151829.