While experimenting with mice that had been specially altered to have no glucocorticoid receptors in their livers, a group of researchers discovered that the mice lost weight when fed the same diet on which normal mice were able to maintain their normal weight (Rose et al., 2011).1 They lost weight because they weren’t able to properly digest fats — they also weren’t able to recycle bile acids. Furthermore, they developed gallstones.
Normally, the gallbladder stores an adequate supply of bile so that bile will be available as needed by the digestive system whenever a meal is eaten. As we become hungry, cortisol (which is a glucocorticoid hormone) is released to attach to glucocorticoid receptors in the liver. The liver responds by producing bile and storing it in the gallbladder to gear up for digesting the next meal. As the next meal is eaten, bile is released through the common bile duct into the small intestine. Lipase from the pancreas is also added to the common bile duct to mix with the bile. The bile emulsifies the fat in the food (breaks it into small globules) and the lipase breaks the globules into much smaller particles.
Bile acid malabsorption (BAM).
The body usually recycles about 95 % of the bile that’s released into the intestine. The reabsorption (recycling) takes place in the terminal ileum, which is the last segment of the small intestine. Any bile that is not recycled, stays in the intestine and passes into the colon. And since it shouldn’t be there, if too much remains, it may cause diarrhea. This scenario is known as bile acid malabsorption (BAM) and it can be a major cause of diarrhea not only for MC patients, but others as well.
But if bile acids are not being properly recycled, the liver may not be able to produce enough bile to maintain a normal level in the gallbladder. If that happens, the digestive system may not be able to digest fat properly, and the patient may begin to lose weight. And too much undigested fat in the stool causes diarrhea. Energy levels will also probably be decreased.
The researchers were able to verify that this effect also apples to humans. The adrenal glands are responsible for producing cortisol. Patients who have been diagnosed with a rare disorder known as Addison’s disease are unable to produce normal amounts of cortisol. Their immune system attacks their adrenal glands and this interferes with their ability to produce normal amounts of cortisol. The researchers discovered that when they analyzed blood samples taken from Addison’s disease patients before and after eating, the samples showed that bile acid recycling was also compromised similar to the mice that had no glucocorticoid receptors in their livers. So therefore cortisol must also control bile acid recycling in humans.
This might have interesting implications for MC patients.
Some patients tend to gain weight during a flare, while others lose weight when their MC is active. It would seem that this scenario might suggest that those MC patients who are unable to properly recycle bile acids might be among those who are more likely to lose weight during a flare. And conversely, those who are able to properly recycle bile acids are less likely to lose weight. This might also imply that those patients who lose weight (or lose it more rapidly) are more likely to respond to cholestyramine treatments than those who are less prone to losing weight during a flare. Please keep in mind that this is strictly speculation at this point, as there is not yet any published research that verifies it as a fact.
It’s highly likely that this explains why corticosteroids are so effective for treating MC and other IBDs. When patients take a corticosteroid, it boosts their ability to recycle bile acids, thus eliminating (or at least minimizing) a major cause of diarrhea. Anti-inflammatory products such as budesonide (Entocort or Uceris) have potent glucocorticoid activity, so they are capable of providing a significant cortisol boost to enhance bile acid reabsorption. This also should explain why so many patients tend to gain weight while taking budesonide or some other corticosteroid.
1. Rose, A. J., Berriel Díaz, M., Reimann, A., Klement, J., Walcher, T., Krones-Herzig, A., . . . Herzig, S. (2011). Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor. Cell Metabolism, 14(1), 123–130. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21723510