Part 1: Dysfunction of Farnesoid X Receptor In the Ileum Driving Liver and Gut Disharmony, A Sustained Cycle In Chronic Fatigue Syndrome.

NOTE: I have decided to revise my theory and attribute the gut-liver axis disharmony to FXR dysfunction rather than over activation. Because of limited resources and data it is difficult to call whether it is over activated or under. Either results in liver-gut disharmony which I still maintain is what drives and sustains CFS. The therapies I have in mind to correct this disharmony are the same regardless of if it is over or under activated.

After many years of relentless research into the condition commonly referred to Chronic Fatigue Syndrome. I have decided to start to releasing my analysis and theory of what I feel has caused and is sustaining this awful condition. The analysis is derived from many areas of medicine, from Neurology to Traditional Chinese Medicine. My research into this condition I feel is reaching the end. I feel its time to submit my findings in order to shed insight into this horrific condition so that people can start to heal.

Due to the overwhelming amount of information I have decided to divide it into a multipart series. I would like to begin with a summary of the theory.

To first understand the viewpoint of this theory, it is important that some fundamental concepts are understood. In Traditional Chinese Medicine (TCM) fatigued based syndromes are often cited as being a disharmony of the Spleen and Liver. In TCM the concept of the Spleen and Liver are not the same as in Western medicine. While the physical Liver is in fact part of the Liver system in TCM, the Spleen many believe refers to pancreatic and gut health. There is a large focus in medicine on gut health, featuring therapies that typically involve high doses of probiotics and other agents to prevent intestinal inflammation. However, what is largely ignored is the need for a healthy functioning liver to maintain proper gut health. Bile synthesis is needed to maintain proper PH balance in the gut, which is critical for maintaining a healthy bacterial balance. It is also needed to stimulate intestinal contractions and breakdown fats.

Much like TCM’s view point, in essence, I believe that at the core of CFS is a dysfunction in signaling between the gut and the liver. This occurs primarily through a receptor called Farnesoid X Receptor (FXR). This receptor, highly expressed in both the liver and the intestines, is a bile acid sensor. It is necessary to maintain many functions of liver and gut. However, dysfunction of Farnesoid X Receptor leads to stagnant liver function, resulting in a fatty and dysfunctional liver condition. What takes place is an epigenetic change in the liver, or a metabolic reprogramming so to speak, that alters liver chemistry to cater to a low energy homeostasis. FXR changes liver energy utilization via an up regulation in something called pyruvate dehydrogenase kinase 4 (PDK4).

The compromised bile flow also results in constipation. Bile is necessary to stimulate intestinal contractions. PWCFS often cite having fluctuations between diarrhea and constipation. Clearly, this will create a perfect environment for leaky gut to set in. The issue that I believe compounds fatigue is that once leaky gut settles in, toxins enter the blood and further compound liver issues. Adding to an already overburdened liver. This I believe is what dictates the more severe cases of fatigue begin. Bile is what carries the toxins from the liver into the intestines to be excreted. Now that the bile is stagnant you start to see low levels of toxin clearance in the liver, further compounding liver dysfunction.

Another interesting note is that a Kidney Dialysis medication called Sevelamer  has been shown to antagonize FXR receptors in the intestine. Mice with Non-Alchoholic Liver Disease were administered this drug and after 12 weeks were shown to have significant reductions in liver steatosis a long with a reversal of innate immune dysregulation. A very common feature in people suffering from CFS.

The scope of all the systems involved in sustaining this condition is massive. I will provide more more analysis over the next few weeks.

Essentially what I am saying is that in CFS is a condition based around a miscommunication between the liver and gut that is mediated via FXR due to alterations in the gut microbiome. It is not simply a liver condition or a gut condition but rather both feeding into each other.

More to come. Below are some links to studies in which I made reference to. Please send me some feedback through the contact if you felt this helped you.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215539/

https://www.ncbi.nlm.nih.gov/labs/articles/27605663/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700422/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629219/

http://news.psu.edu/story/288862/2013/09/24/research/adjusting-bacteria-intestines-may-lead-obesity-treatments

http://www.nature.com/articles/ncomms3384

https://www.researchgate.net/publication/51773581_Selective_Activation_of_Nuclear_Bile_Acid_Receptor_FXR_in_the_Intestine_Protects_Mice_Against_Cholestasis

https://www.researchgate.net/publication/8012731_Regulation_of_pyruvate_dehydrogenase_kinase_expression_by_the_farnesoid_X_receptor

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