DR. Innovations

Bile Acid Metabolism Pathways

Fat digestion requires the function of many different organs and microbes working in tandem for it to occur. Any kink along the pathway of fat digestion can cause it to not be assimilated properly and cause fat to be dumped into the stool and improper amounts of bile either be produced or utilized. If you are having lipid digestive issues, your stool will either look yellow (from undigested lipids concentrating in the stool) or very oily. You might get urgent diarrhea from eating a high fat meal from bile not being reabsorbed properly. Finally, you may become constipated and your stool might become dry and light brown or clay colored from not producing enough bile. All these stool changes are warning signs of poor bile production and utilization and fat digestion and assimilation issues.

So how is fat digested and assimilated by our body?

1. Food that contains fat enters the stomach.

2. Soluble fats like some medium chain triglycerides (capryic acid) are soluble in the stomach and absorbed immediately.

3. The liver begins to synthesize bile salts (which is dark green to yellowish brown) from cholesterol. The liver hepatocytes metabolize cholesterol into cholic acid and chenodeoxycholic acid which are conjugated with the amino acids glycine and taurine to form bile salts. Bilirubin is conjugated with glucuronic acid making it water soluble and is released into the bile to be eliminated by the gastrointestinal system. Bilirubin attaches itself to our stool and very little is reabsorbed later, unlike bile. Bilirubin is metabolized by colonic bacteria in the stool which is what makes our stool turn brown. Bile is then stored in the gallbladder for future use or released directly into the duodenum when the hormone cholecystokinin (CCK) is produced (bile release directly into the duodenum occurs mainly in people who have had their gallbladder removed).

4. Insoluble fats like oleic acid (found heavily in olives) are released into the duodenum through the digestive process. The hormone prosecretin is produced by the S cells in the duodenum and activated into secretin by stomach chyme entering the duodenum. Secretin triggers the liver to produce bile and the pancreas to produce sodium bicarbonate to neutralize the high pH of stomach chyme and to increase the functionality of the digestive enzymes pancreatic lipase (which digests fats) and amylase (which digests carbohydrates). CCK is produced by the duodenal enteroendocrine cells while stomach cyme enters the duodenum as well.

5. CCK causes bile salts to release into the duodenum (mainly from gallbladder contractions and the relaxation of the sphincter of Oddi) to start the emulsification of fats. CCK also later triggers the pancreas to release pancreatic juice that contains digestive enzymes and bicarbonate through relaxation of the sphincter of Oddi. Finally, bile is alkaline which helps further neutralize stomach chyme and is also antimicrobial to some species of bacteria that cannot metabolize bile.

6. Fats break down into mixed miscelles (aggregate of molecules in a colloidal solution, such as those formed by detergents).

7. Lipase is released by the pancreas and miscelles are further broken down into free fatty acids and glycerides.

8. The free fatty acids and glycerides are absorbed through the intestinal mucosa and are reconverted to tricyglycerides. The triglycerides aggregate with cholesterol and apolipoprotein. The byproducts enter the lymphatic system and then into the bloodstream where they are used by the body for fuel, resterfied and stored in adipose tissue, or are processed further by the liver by endocytosis.

9. Bile salts are actively reabsorbed toward the end of the ileum back into hepatic recirculation. Some of our gut bacteria deconjugate bile acids back to lipid- soluble bile acids which are passively reabsorbed. Bacteria deconjugate bile to protect themselves from its antimicrobial effects for survival. Finally, our gut bacteria convert some of the primary bile salts to secondary conjugated bile salts, which can help improve fat digestion and assimilation.

10. Excess fat, if any, is eliminated through the stool. The body performs many different processes that must work like a well-oiled machine to digest and assimilate fat properly. If there is any issue during the fat digestion process, the body may be able to compensate for a time, but eventually you will start suffering from digestive issues.

What Causes Poor Fat Digestion?

There are many different causes of poor fat digestion and they range from:

 Upper gut dysbiosis. For example, overgrowth of the Gram-negative bacteria Prevotella, which, can deconjugate bile, has been shown to cause bile acid malabsorption, diarrhea, yellow and greasy stools, hindered fat assimilation, and cause liver, gallbladder, and pancreatic inflammation. Parasites, bacterial biofilm, and yeast (balls of fungus) can block ducts and cause biliary sludge or gallstones to develop.

 Sphincter of Oddi dysfunction

 Diarrhea

 Diet can also cause poor fat digestion. Improperly following high fat diets like ketogenic diets. The standard American diet, for example, which is very high

in fat and carbohydrates strain the liver by making it produce excessive bile for increased fat digestion and the excess carbohydrates leading to dysbiosis in the upper gut.

 Pancreatic insufficiency

 Bile production insufficiency

 Gallstones blocking bile being released properly into the duodenum

 Pancreatitis

 Liver and gall bladder inflammation

 Cirrhosis of the liver

 SIBO (small intestinal bacterial overgrowth)

 Hypochlorhydria (low stomach acid production or elevated pH stomach chyme)

 Liver and gallbladder congestion (bile not being released properly, stagnant bile)

 Rapid dumping syndrome (mainly occurs from having a cholecystectomy, or known as gallbladder removal surgery)

 Bile acid malabsorption

 Gastric bypass surgery

 Viral gastroenteritis (Norovirus requires bile to propagate, so the body reduces production and release to hinder the virus; if this is occurring your stool should become light brown or pale)

 Liver, gallbladder, pancreatic, or intestinal cancer

 Structural or birth defects in the biliary system

 Biliary or pancreatic duct strictures (from intestinal surgeries or birth defects)

 Sclerosing cholangitis (inflammation of the bile ducts)

 Cysts within the bile ducts (mainly caused by dysbiosis)

 Liver fibrosis

 Cystic fibrosis (people with cystic fibrosis tend to suffer from increased biliary sludge and more acidic bile)

 Hepatitis

 Medications like cholestyramine that bind bile

So how do you know if you produce too little or too much bile?

Generally, if you do not produce not enough bile or your bile is slugish your stool will appear to be clay colored or pale from a lack of bilirubin being deposited in your stool mixed with bile. You may also see yellow in your stool or your stool may look greasy (steatorrhea) from improper production of bile that may lead to fat being deposited into your stool instead of being absorbed and utilized by the body. You may also become constipated from a lack of bile production as the stool becomes sticky and hard to pass. People that do not produce enough bile may have nutrient deficiencies in fat soluble vitamins including vitamin A, vitamin D, vitamin E, and vitamin K2. Bile also increases the absorption of the mineral calcium and a lack of it may lead to calcium deficiency. Bile neutralizes stomach chime pH with sodium bicarbonate and a lack of it can lead to more acid stomach chime which can lead to a more acidic small intestine, leading to inflammation, lack of absorption that requires pH, and dysbiosis from certain bacteria that thrive in a more acidic small intestine. Finally, a lack of bile production can lead to microbiome dysbiosis because bile is a bactericide against many bacteria that are unable to metabolize it. Lack of bile production can come from deficiencies in the amino acids glycine and taurine that are required to bind bile acids, blocked bile ducts, or your gallbladder containing many gallstones. A lack of bile can also come from microbes that deconjugate bile leading it to be ineffective. Medications that bind bile like cholestyramine can also cause clay colored schools and improper fat assimilation, increased binding and elimination of thyroid hormones (may lead to or worsen hypothyroidism), and reduction in cholesterol synthesis by the liver. Many people who suffer from improper bile production and release suffer from dysbiosis that would normally be controlled by bile, and the dysbiosis can cause bloating and make their digestion worse. Finally, reduction in bile production or release may lead to a buildup of bilirubin in the bloodstream leading to yellowing of the skin or eyes known as Jaundice. Some people suffering from poor liver and gallbladder health, gastrointestinal surgery, cholecystectomy, dysbiosis (bile deconjugation from bacteria), celiac disease, Crohn’s disease (ileal inflammation), ileal resection, overproduction of bile, might have diarrhea and yellow, greasy stools from bile acid malabsorption or production of too much bile. Bile acids are produced in the liver for fat digestion and are stored in the gallbladder for future use. Bile acids during digestion are reabsorbed in the terminal ileum of the small intestine and are recycled through the liver. These bile acids are then stored again in the gallbladder for future use. In people with upper gut digestive issues, bile acids may not be reabsorbed properly, deconjugated by dysbiosis, or too much bile is produced causing an excessive amount of bile acids traveling further into the large intestine. When bile salts make it into the large intestine, they stimulate extra water secretion and intestinal motility creating chronic diarrhea and usually abdominal cramping. Severe bile acid malabsorption can trigger rapid dumping syndrome (severe diarrhea, thirty minutes to a couple of hours after eating) if the person consumes a high fat meal and is suffering from fat digestion issues.