Over Activation of Farnesoid X Receptor In the Ilium Driving Liver and Gut Disharmony

[Bdeep86]

Hi @Bdeep86 - I completely understand your caution around this - we are all desperate for relief so I think there is an evident tendency to latch onto anything that might help..

I'm fairly cautious as have tried things in the past that have made me feel worse - hence the TUDCA has been sitting in my kitchen untouched for a couple of weeks and it will stay there until I feel confident I've done the groundwork. I did try Biotics Research Beta-TCP ("Support for normal cholesterol to bile acid conversion and healthy bile flow. Contains digestive and antioxidant enzymes, vitamin C, taurine and organic beet concentrate.") to support gall bladder but felt really rough pretty quickly - so not wanting to be hasty with the TUDCA....

And it's the groundwork I'm interested in at the moment. Should all sugar, including fruit be excluded? and presumably this is because of the dysbiosis inherent in the whole picture? I haven't been rigorous about sugar but I'm not getting any better....

I would have to know more but I feel that most people who have had CFS long term can't take TUDCA right off the bad. Also your diet will be critical to this. If you have a collapsed liver/gallbladder channel then it can actually make things worse. Most are going to need other support before addressing the collapse liver/gallbladder channel.

Sugar by in large needs to be eliminated. Fat intake is a major part of this picture as well. Fruit aside from bananas and avacado are actually alright as long as they are eaten by themselves and at least 2 hours away from other foods. Preferably these will be cooked as well, something like baked apples for example. Are you craving sugar? Are you gluten intolerant? I saw you aren't breaking down protein, I think this is the case for most CFS sufferers.

 

[jump44]

What do you think of taking Taurine as opposed to TUDCA at least initially? Taurine has many of the same benefits to me but isnt quite as powerful-and has a lot of other benefits on electrolytes etc as well, seems when I run out of it I notice a difference for the worse. Its also way cheaper.

 

[Hilary]

I would have to know more but I feel that most people who have had CFS long term can't take TUDCA right off the bad. Also your diet will be critical to this. If you have a collapsed liver/gallbladder channel then it can actually make things worse. Most are going to need other support before addressing the collapse liver/gallbladder channel.

Sugar by in large needs to be eliminated. Fat intake is a major part of this picture as well. Fruit aside from bananas and avacado are actually alright as long as they are eaten by themselves and at least 2 hours away from other foods. Preferably these will be cooked as well, something like baked apples for example. Are you craving sugar? Are you gluten intolerant? I saw you aren't breaking down protein, I think this is the case for most CFS sufferers.

I've had it over 20 years. I had gall bladder pain early on and digestive issues have certainly got steadily worse. Gall bladder was demonstrably sluggish at least 10/12 years ago though no stones but they have developed in the last couple of years as well.

I get a bit of a sugar craving, not massive. Also crave cheese when I'm hungry and need something speedy.
I don't know if I'm gluten intolerant though am 2 weeks into being gluten free and will test it out in a couple of weeks. I'm not feeling better for excluding it so far.
Fats I use (cold or heated ) are olive oil, butter and coconut oil plus (on salads not for cooking) hemp oil, pumpkin seed oil and walnut. I have just restarted fish oil which helps with pain. Also take phosphatidylcholine when I remember. I do find sugary stuff has a noticeable adverse effect on digestion and the OAT result indicates high yeast.

I think it's fairly clear I need to improve diet as things are so out of whack. I shall keep off the TUDCA for the moment.. Easy enough to keep fruit consumption away from other food - though I'm surprised avocados (I eat a lot) are off limits? Appreciate your input, thank you. I feel as though I'm looking for the proverbial needle in a haystack.

 

[aquariusgirl]

http://onlinelibrary.wiley.com/doi/10.1111/imr.12579/abstract

 

[Gondwanaland]

http://onlinelibrary.wiley.com/doi/10.1111/imr.12579/abstract

INVITED REVIEW
Interactions between bile salts, gut microbiota, and hepatic innate immunity
First published: 30 August 2017

Summary
Bile salts are the water-soluble end products of hepatic cholesterol catabolism that are released into the duodenum and solubilize lipids due to their amphipathic structure. Bile salts also act as endogenous ligands for dedicated nuclear receptors that exert a plethora of biological processes, mostly related to metabolism. Bile salts are actively reclaimed in the distal part of the small intestine, released into the portal system, and subsequently extracted by the liver. This enterohepatic cycle is critically dependent on dedicated bile salt transporters. In the intestinal lumen, bile salts exert direct antimicrobial activity based on their detergent property and shape the gut microbiota. Bile salt metabolism by gut microbiota serves as a mechanism to counteract this toxicity and generates bile salt species that are distinct from those of the host. Innate immune cells of the liver play an important role in the early recognition and effector response to invading microbes. Bile salts signal primarily via the membrane receptor TGR5 and the intracellular farnesoid-x receptor, both present in innate immune cells. In this review, the interactions between bile salts, gut microbiota, and hepatic innate immunity are discussed.

 

[NotThisGuy]

same here.
CFS onset with-> lack of bile flow, undigested food in stool, SIBO.
Shortly after taking cyanocobalamin and lead exposure.

Only since over 2 years I had only 3 times "normal" stool. Well formed, well digested and nice brown color.
First time was with my first dose of pantothenic acid 500mg. Never worked again after that.
Second time was first sunbath in the sun this summer. Never worked again after that.
Third time was after completely avoiding orgasms for few weeks. Again it seems to have stopped working.

Dont know where the connection is... HPA or adrenals or something else..

I read in a mast cell forum of someone who always gets yellow stools when he stops his mast cell medication or eat something with very high histamines.

 

[Gondwanaland]

Did I understand it wrong or these 2 studies contradict one another?

https://www.ncbi.nlm.nih.gov/pubmed/28111285
Biochim Biophys Acta. 2017 May;1862(5):496-512. doi: 10.1016/j.bbalip.2017.01.007. Epub 2017 Jan 19.
The interrelationship between bile acid and vitamin A homeostasis.

Abstract
Vitamin A is a fat-soluble vitamin important for vision, reproduction, embryonic development, cell differentiation, epithelial barrier function and adequate immune responses. Efficient absorption of dietary vitamin A depends on the fat-solubilizing properties of bile acids. Bile acids are synthesized in the liver and maintained in an enterohepatic circulation. The liver is also the main storage site for vitamin A in the mammalian body, where an intimate collaboration between hepatocytes and hepatic stellate cells leads to the accumulation of retinyl esters in large cytoplasmic lipid droplet hepatic stellate cells. Chronic liver diseases are often characterized by disturbed bile acid and vitamin A homeostasis, where bile production is impaired and hepatic stellate cells lose their vitamin A in a transdifferentiation process to myofibroblasts, cells that produce excessive extracellular matrix proteins leading to fibrosis. Chronic liver diseases thus may lead to vitamin A deficiency. Recent data reveal an intricate crosstalk between vitamin A metabolites and bile acids, in part via the Retinoic Acid Receptor (RAR), Retinoid X Receptor (RXR) and the Farnesoid X Receptor (FXR), in maintaining vitamin A and bile acid homeostasis. Here, we provide an overview of the various levels of "communication" between vitamin A metabolites and bile acids and its relevance for the treatment of chronic liver diseases.

https://www.ncbi.nlm.nih.gov/pubmed/20233723
J Biol Chem. 2010 May 7;285(19):14486-94. doi: 10.1074/jbc.M110.116004. Epub 2010 Mar 16.
Regulation of bile acid synthesis by fat-soluble vitamins A and D.

Abstract
Bile acids are required for proper absorption of dietary lipids, including fat-soluble vitamins. Here, we show that the dietary vitamins A and D inhibit bile acid synthesis by repressing hepatic expression of the rate-limiting enzyme CYP7A1. Receptors for vitamin A and D induced expression of Fgf15, an intestine-derived hormone that acts on liver to inhibit Cyp7a1. These effects were mediated through distinct cis-acting response elements in the promoter and intron of Fgf15. Interestingly, transactivation of both response elements appears to be required to maintain basal Fgf15 expression levels in vivo. Furthermore, whereas induction of Fgf15 by vitamin D is mediated through its receptor, the induction of Fgf15 by vitamin A is mediated through the retinoid X receptor/farnesoid X receptor heterodimer and is independent of bile acids, suggesting that this heterodimer functions as a distinct dietary vitamin A sensor. Notably, vitamin A treatment reversed the effects of the bile acid sequestrant cholestyramine on Fgf15, Shp, and Cyp7a1 expression, suggesting a potential therapeutic benefit of vitamin A under conditions of bile acid malabsorption. These results reveal an unexpected link between the intake of fat-soluble vitamins A and D and bile acid metabolism, which may have evolved as a means for these dietary vitamins to regulate their own absorption.