Does anyone know something about bile acids?

[space8]

I touched on this topic on here a couple of years ago but I'm so, so tired of not having answers to the bile acids issues I'm having as I'm suspecting it's contributing to my overall poor health and possibly even my ME/CFS symptoms, and most certainly my gastro symptoms.

So I just really need to try to throw this out there again in case anyone would know something about it. I've been suffering from IBS and ME/CFS for years and years and finally found out I had some issues with my bile production after many years without any clues.

I have low levels of 7α-Hydroxy-4-cholesten-3-one indicating cholestasis and elevated unconjugated/secondary bile acids in serum + fat malabsorption. No elevated levels of conjugated/primary bile acids in serum. Normal liver enzymes and bilirubin, weird liver/gallbladder ultrasound but later normal MRI. My doctor who's an expert of bile acids and liver diseases has never seen this in any patient before (i.e. results indicating cholestatic liver disease in the absence of elevated liver enzymes and/or any evidence of liver disease).

I'm super frustrated with this as it feels like I'm close to an answer to what's going on but I'm just stuck with these results and nothing to explain them. I've considered anything from inborn errors of bile acid synthesis, but that almost always presents itself in childhood. I've even considered some type of atypical cystic fibrosis (as cystic fibrosis patients often have poor bile production).

My doctor think it might have to do with my microbiota somehow, but what's causing my microbiota to be off to begin with? And what does elevated secondary bile acids imply, when I don't have elevated primary bile acids? And what health implications are there of having elevated secondary bile acids in serum? Can that in itself contribute to health issues? Why is my bilirubin levels normal when my bile acids aren't? So many questions that I feel like no one has answered for me.

I've been trying my absolute hardest to read up on the topic and have searched trough the entire web for an explanation, but I hit a wall every time. The bile acid synthesis is super complicated and much less is written about it compared to other conditions.

Please say there happens to be some bile/liver experts on here! I really need some guidance on how to move forward with these results. Does anyone know anything about this topic? I'm happy with breadcrumbs as long as it's something. I'm just really frustrated to be in the dark about this.

 

[LINE]

May be of some help?

https://www.frontiersin.org/article...n lead to increased colonization by pathogens.

Taurine in synthesis of bile
https://pubmed.ncbi.nlm.nih.gov/31468384/

Role of choline (phosphatidylcholine) in bile production
https://pubmed.ncbi.nlm.nih.gov/9748591/

 

[Flnn]

From my research, I have found out that high-fat diets (that includes the keto diet as well) are producing many bile salts, which feed the hydrogen sulfide-producing bacteria, and hydrogen sulfide gas contributes to leaky gut also known as intestinal permeability.

By eating a high-fat diet, there is an overproduction of bile. The bacteria are eating the bile and now you have an overproduction of hydrogen sulfide gas.

The bugs that eat bile are growing and you'll have a dysbiosis on the microbiome.

Bilophila seems to be problematic and abundant in a Western Diet

Desulfovibrio and Bilophila are Hydrogen Sulfide gas producers - they can cause gut inflammation and visceral hypersensitivity!

A dysregulated bile acid-gut microbiota axis contributes to obesity

The Role of the Gut Microbiota in Bile Acid Metabolism

Intestinal Bacteria Interplay With Bile and Cholesterol Metabolism: Implications on Host Physiology



Have you ever made a gut microbiome analysis?

How is your diet?

 

[kangaSue]

I'm trying to learn about bile acids too so no expert on the subject. What effect is this having on bowel function, diarrhea or constipation?

Do you know what your fibroblast growth factor 19 (FGF19) level is?

(Bile acids stimulate the nuclear farsenoid X receptor (FXR), which acts as main nuclear BA receptor and increases FGF19 level. In bile acid malabsorption causing diarrhea, 7aC4 is increased and FGF19 is reduced as a general rule)

According to the following reference;
[There are 4 major individual fecal BAs found in human stool: chenodeoxycholic acid (CDCA), cholic acid (CA), lithocholic acid, and deoxycholic acid (DCA). These are classified as primary or secondary and secretory or nonsecretory. Primary BAs are directly synthesized by the liver and include CDCA and CA. Upon entering the colon, these primary BAs are deconjugated and then dehydroxylated by colonic bacteria, resulting in the formation of secondary fecal BAs, namely, DCA and lithocholic acid. Secretory fecal BAs stimulate both colonic secretion and motility and include CDCA and DCA. ]
https://www.gastrojournal.org/article/S0016-5085(18)35400-3/fulltext

I gather that this would be why your doctor is saying it's something to do with the microbiome.

An interesting testing caveat was also mentioned in this article;
[7aC4 is measured by high-performance liquid chromatography (HPLC) with mass spectrometry, and FGF19 is evaluated with enzyme-linked immunosorbent assay. It is important to note that both C4 and FGF19 have diurnal variations, with a gradual increase after 9:00 AM. If samples are taken after 9:00 AM, the fasting serum biomarkers may result in higher values because of the diurnal variations, but not indicate true elevated hepatic BA synthesis.]

 

[Pearshaped]

Have they checked you for PBC?
Im not sure they can see it on MRI (?)
Taurine powder helps me a lot to digest but didnt solve my IBS problem.

 

[mariovitali]

I have low levels of 7α-Hydroxy-4-cholesten-3-one indicating cholestasis and elevated unconjugated/secondary bile acids in serum + fat malabsorption. No elevated levels of conjugated/primary bile acids in serum.

May i ask what kind of test showed this abnormal result? Obviously this is not the standard test of total bile acids.

 

[space8]

May be of some help?

https://www.frontiersin.org/articles/10.3389/fmicb.2017.01581/full#:~:text=Bile salts are potent antimicrobial agents and are,levels can lead to increased colonization by pathogens.

Taurine in synthesis of bile
https://pubmed.ncbi.nlm.nih.gov/31468384/

Role of choline (phosphatidylcholine) in bile production
https://pubmed.ncbi.nlm.nih.gov/9748591/

Thank you LINE! Any and all studies on this topic are super appreciated. The issue is just figuring out what applies to me and what doesn’t. I follow this up once a year to see that nothing has worsened. Other than that doctors have pretty much given up on diagnosing the condition. So it kinda feels like it’s up to me having a hypothesis and push for something, which is a bit of a shame. But at least my doctor really did try to test for some things before dropping it. I’m just not pleased because I know you could probably figure this one out if I just got one more piece of the puzzle. Getting there is the difficult part ...

 

[space8]

From my research, I have found out that high-fat diets (that includes the keto diet as well) are producing many bile salts, which feed the hydrogen sulfide-producing bacteria, and hydrogen sulfide gas contributes to leaky gut also known as intestinal permeability.

By eating a high-fat diet, there is an overproduction of bile. The bacteria are eating the bile and now you have an overproduction of hydrogen sulfide gas.

The bugs that eat bile are growing and you'll have a dysbiosis on the microbiome.

Bilophila seems to be problematic and abundant in a Western Diet

Desulfovibrio and Bilophila are Hydrogen Sulfide gas producers - they can cause gut inflammation and visceral hypersensitivity!

A dysregulated bile acid-gut microbiota axis contributes to obesity

The Role of the Gut Microbiota in Bile Acid Metabolism

Intestinal Bacteria Interplay With Bile and Cholesterol Metabolism: Implications on Host Physiology



Have you ever made a gut microbiome analysis?

How is your diet?

Thank you so much! There were some really great papers in there. Many of which I hadn’t seen before.

My diet right now is pretty balanced. My BMI is 19,9. I eat equal amounts of carbs, proteins, fats. But I was on keto a couple of years ago. However, only because I couldn’t tolerate ANY carbs due to my IBS.

I have tested my microbiota previously and it was pretty bad at the time. I had no growth of beneficial bacteria (Lactobacillus, Bifidobacterium) and a really low variety of bacterial strains. No infection as far as I understood (even though I don’t exclude that an infection potentially triggered my IBS and my ME/CFS once as the onset was very sudden). And too much of total fecal fats and protein products. It was also something about being low (or high - I don’t remember) on total Short Chain Fatty Acids. Fat malabsorption is of course consistent with bile issues. I have since then gotten treatment for my lack of beneficial flora (FMT’s performed by a doctor) and feel significantly better gastrointestinal wise, my food intolerances aren’t nearly as bad. My fatigue is much better too.

My health is still really shit in many ways though. My gut flora is certainly in a better state (considering the above), but my bile acid results persists. I still get bad PEM, I still have nervous system issues, my energy is not what it’s supposed to be for my age, my mental tenacity is really low, I feel really weak and weird almost every day, I don’t tolerate any alcohol (which I don’t have to drink obviously, but it would be nice to know why I can’t drink a single glass without feeling poisoned. It’s probably also related to my bile/potential liver issues). I still have to pace myself properly. If I get one hour too little sleep I feel like I’m dying. Stuff like that. I really feel like I’m 80 and it’s hard to appreciate life under those circumstances (which I’m sure many here are aware of) even though I have more energy now than I once did.

I at least want to know if this thing can explain my symptoms even though I’m open to some of it ”just” being ME/CFS. But how do I know that for sure when I don’t understand these biomarkers that could very well be a sign of other processes creating part of the issues I’m experiencing. I also recently found out I have PCOS. So maybe there’s some type of metabolic component there too since PCOS is related to metabolic syndrome.

Thank you so much again for helping!

 

[space8]

I'm trying to learn about bile acids too so no expert on the subject. What effect is this having on bowel function, diarrhea or constipation?

Do you know what your fibroblast growth factor 19 (FGF19) level is?

(Bile acids stimulate the nuclear farsenoid X receptor (FXR), which acts as main nuclear BA receptor and increases FGF19 level. In bile acid malabsorption causing diarrhea, 7aC4 is increased and FGF19 is reduced as a general rule)

According to the following reference;
[There are 4 major individual fecal BAs found in human stool: chenodeoxycholic acid (CDCA), cholic acid (CA), lithocholic acid, and deoxycholic acid (DCA). These are classified as primary or secondary and secretory or nonsecretory. Primary BAs are directly synthesized by the liver and include CDCA and CA. Upon entering the colon, these primary BAs are deconjugated and then dehydroxylated by colonic bacteria, resulting in the formation of secondary fecal BAs, namely, DCA and lithocholic acid. Secretory fecal BAs stimulate both colonic secretion and motility and include CDCA and DCA. ]
https://www.gastrojournal.org/article/S0016-5085(18)35400-3/fulltext

I gather that this would be why your doctor is saying it's something to do with the microbiome.

An interesting testing caveat was also mentioned in this article;
[7aC4 is measured by high-performance liquid chromatography (HPLC) with mass spectrometry, and FGF19 is evaluated with enzyme-linked immunosorbent assay. It is important to note that both C4 and FGF19 have diurnal variations, with a gradual increase after 9:00 AM. If samples are taken after 9:00 AM, the fasting serum biomarkers may result in higher values because of the diurnal variations, but not indicate true elevated hepatic BA synthesis.]

Oh, I actually don’t think they’ve ever tested my Fibroblast growth factor. That’s actually a really, really good reminder. Thank you!! Especially since I read that:

”Patients with the metabolic syndrome, non-alcoholic fatty liver disease and insulin resistance have reduced levels of FGF19.[39][40] FGF19 increases to normal values in obese patients who undergo Roux-en-Y gastric bypass and other types of bariatric surgery.”

I just found out I have PCOS too, which is a type of metabolic syndrome according to some since it’s often thought to be made worse/be caused by insulin resistance.

The interesting part is that in bile acid diarrhoea you often see high levels of 7α-Hydroxy-4-cholesten-3-one, but I had (severe) IBS-D with low levels of 7α-Hydroxy-4-cholesten-3-one. Not much is known about bile acids in human disease. Regular GPs won’t know about it for sure - unfortunately.

 

[space8]

Have they checked you for PBC?
Im not sure they can see it on MRI (?)
Taurine powder helps me a lot to digest but didnt solve my IBS problem.

Thank you for contributing! I haven’t been tested for PBC directly but have taken my liver enzymes several times and they’ve always been within range on the lower side of the spectrum (hitherto). I think that’s why they’ve never done a liver biopsy or anything like that, because my enzymes are within range. But two of my close relatives just got diagnosed with PSC and PBC so it seems a little suspicious.

 

[space8]

May i ask what kind of test showed this abnormal result? Obviously this is not the standard test of total bile acids.

Of course! The 7α-Hydroxy-4-cholesten-3-one was the one indicating a ”low” bile acid synthesis. Total bile acids were fine. Then my doctor sent me for some special testing in which I got to measure my unconjugated bile acids. I unfortunately don’t know what that one was called as it was done in the clinic using some special method (otherwise I go to a regular lab to have testing done). I only know they were elevated. So, I’m sorry I can’t name the last one!

 

[Flnn]

Thank you so much! There were some really great papers in there. Many of which I hadn’t seen before.

No problem! You are welcome!

My diet right now is pretty balanced. My BMI is 19,9. I eat equal amounts of carbs, proteins, fats. But I was on keto a couple of years ago. However, only because I couldn’t tolerate ANY carbs due to my IBS.

I have personally found that a vegetarian/vegan diet works the best. By having such a diet you are not ingesting any saturated fats, but only unsaturated like avocado, nuts, seeds, olives, peanuts, etc.

There are so many benefits to a vegetarian diet!

From what I understood, Bilophila is growing on saturated fats.

I have tested my microbiota previously and it was pretty bad at the time. I had no growth of beneficial bacteria (Lactobacillus, Bifidobacterium) and a really low variety of bacterial strains. No infection as far as I understood (even though I don’t exclude that an infection potentially triggered my IBS and my ME/CFS once as the onset was very sudden). And too much of total fecal fats and protein products. It was also something about being low (or high - I don’t remember) on total Short Chain Fatty Acids. Fat malabsorption is of course consistent with bile issues. I have since then gotten treatment for my lack of beneficial flora (FMT’s performed by a doctor) and feel significantly better gastrointestinal wise, my food intolerances aren’t nearly as bad. My fatigue is much better too.

Lactobacillus and Bifido are extremely important bugs even though they are present in a small % in the gut.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964481/ Probiotic Species in the Modulation of Gut Microbiota: An Overview

This paper provides a broad review of several Lactobacillus spp., Bifidobacterium spp., and other coliform bacteria as the most promising probiotic species and their role in the prevention of degenerative diseases, such as obesity, diabetes, cancer, cardiovascular diseases, malignancy, liver disease, and inflammatory bowel disease.

Diversity of the microbiome is key for good health! Antibiotics can have a dramatic effect on the diversity of the microbiome!

SCFA are very important as well - they are a major source of energy for colon cells, plus very healing for the brain...

I guess overall there must be paid great attention to everything in the digestive system like checking the gut microbiome, checking the small intestine for SIBO, intestinal permeability, rebalancing everything up, changing the diet, eating at a right time with enough space in between meals without snacks and making sure to not mix sweet fruits with acid fruits nor fruits with legumes at the same meal, etc and I guess the gallbladder, the liver, and the pancreas slowly will heal and everything will start working as it should...

My health is still really shit in many ways though. My gut flora is certainly in a better state (considering the above), but my bile acid results persists. I still get bad PEM, I still have nervous system issues, my energy is not what it’s supposed to be for my age, my mental tenacity is really low, I feel really weak and weird almost every day, I don’t tolerate any alcohol (which I don’t have to drink obviously, but it would be nice to know why I can’t drink a single glass without feeling poisoned. It’s probably also related to my bile/potential liver issues). I still have to pace myself properly. If I get one hour too little sleep I feel like I’m dying. Stuff like that. I really feel like I’m 80 and it’s hard to appreciate life under those circumstances (which I’m sure many here are aware of) even though I have more energy now than I once did.

Gut and nervous system issues are very related. I understand, we are all in the same boat. Have you ever done an ammonia serum test?

 

[mariovitali]

@space8

Then my doctor sent me for some special testing in which I got to measure my unconjugated bile acids. I unfortunately don’t know what that one was called as it was done in the clinic using some special method (otherwise I go to a regular lab to have testing done). I only know they were elevated. So, I’m sorry I can’t name the last one!

Is there a possibility to call the center and/or doctor to get the name of the test you had?


also for your mention :

weird liver/gallbladder ultrasound but later normal MRI

What does "weird" ultrasound exactly mean?

 

[dave11]

Years ago, I thought I had low bile production. I tried lots of bitters with only moderate success. One of the best items I used was boldo tea. It is reputed to increase bile flow.

Later on, I found that I did not need boldo or bitters. Instead, I used high levels of probiotics which proved much more effective. I still take probiotics to this day
.
https://rain-tree.com/boldo.htm

 

[lint7]

@space8 have you had any facial fat loss or lipodystrophy? Your mention of insulin resistance and possible bile salt deficiency might have something in common with what I am suffering from.

 

[space8]

No problem! You are welcome!

I have personally found that a vegetarian/vegan diet works the best. By having such a diet you are not ingesting any saturated fats, but only unsaturated like avocado, nuts, seeds, olives, peanuts, etc.

There are so many benefits to a vegetarian diet!

From what I understood, Bilophila is growing on saturated fats. Lactobacillus and Bifido are extremely important bugs even though they are present in a small % in the gut. Diversity of the microbiome is key for good health! Antibiotics can have a dramatic effect on the diversity of the microbiome! SCFA are very important as well - they are a major source of energy for colon cells, plus very healing for the brain...

I guess overall there must be paid great attention to everything in the digestive system like checking the gut microbiome, checking the small intestine for SIBO, intestinal permeability, rebalancing everything up, changing the diet, eating at a right time with enough space in between meals without snacks and making sure to not mix sweet fruits with acid fruits nor fruits with legumes at the same meal, etc and I guess the gallbladder, the liver, and the pancreas slowly will heal and everything will start working as it should...

Thank you so much again! I wanted to go vegetarian a couple of years ago but since I had a really hard time tolerating carbs I switched to LCHF/keto for the convenience of it. I will definitely consider going vegetarian/vegan again but I really need a meal plan for it to work. I will look at it.

Yeah, microbiome diversity is certainly vital. Mine was soo bad. Considering my gastro symptoms have improved so massively I'm assuming my flora is already a lot better but keeping up a healthy diet will probably help in terms of keeping it that way. I already eat pretty healthy but I could do better.

Gut and nervous system issues are very related. I understand, we are all in the same boat. Have you ever done an ammonia serum test?

I've never done an ammonia serum test, no. What would elevated results suggest? Intestinal permeability? Something else? Thank you!!

 

[space8]

@space8

Is there a possibility to call the center and/or doctor to get the name of the test you had? also for your mention: What does "weird" ultrasound exactly mean?

I will ask the next time I visit. I'm so stressed out by doctors and doctor's visits that I do my absolute best to avoid being in contact with them by phone or otherwise. (Sorry, but I've been ill since I was a teenager and my heart sinks whenever I have to do anything in relation to my health ... even writing in this thread is a little difficult. I keep trying because I want to live a full life without distressing symptoms but it's very difficult mental wise, so I'd rather not call them unless absolutely necessary).

The weird ultrasound showed enlargement of the liver and something with my bile ducts if I remember it correctly. But since they didn't see anything strange when following up with an MRI I suppose they ruled out there being any structural clues as to why I'm having elevated (unconj.) bile acids etc/low bile production.

 

[space8]

Years ago, I thought I had low bile production. I tried lots of bitters with only moderate success. One of the best items I used was boldo tea. It is reputed to increase bile flow.

Later on, I found that I did not need boldo or bitters. Instead, I used high levels of probiotics which proved much more effective. I still take probiotics to this day
.
https://rain-tree.com/boldo.htm

Thank you so much Dave! I will read up on it!

 

[space8]

@space8 have you had any facial fat loss or lipodystrophy? Your mention of insulin resistance and possible bile salt deficiency might have something in common with what I am suffering from.

No, I haven't. My face is pretty round and full (not due to being overweight, it's just like that naturally). I haven't confirmed I have insulin resistance but many believe PCOS (polycystic ovary syndrome) is fuelled by a sensitivity to glucose. So glucose somehow influence the function of your ovaries which will, if they're unhealthy, produce an abnormal amount of androgens. That's one theory.

What are you suffering from that's related to bile salts/insulin resistance, if I may ask?

Thank you for commenting!

 

[Flnn]

Thank you so much again! I wanted to go vegetarian a couple of years ago but since I had a really hard time tolerating carbs I switched to LCHF/keto for the convenience of it. I will definitely consider going vegetarian/vegan again but I really need a meal plan for it to work. I will look at it.

You can watch Forks Over Knives Documentary, What The Health Documentary, The China Study. For meal plans, you can check on Youtube for "Simnett Nutrition". This guy is a Vegan Bodybuilder, Certified Nutritionist Practitioner if I am not mistaken - you can find meal plans for free by watching his videos, he also offers consultations, has some ebooks I think.

Here is a playlist for recipes from his channel:

I've never done an ammonia serum test, no. What would elevated results suggest? Intestinal permeability? Something else? Thank you!!

Hyperammonemia

Ammonia levels rise if the liver is unable to metabolize this toxic compound as a result of an enzymatic defect or hepatocellular damage. The levels may also rise if portal blood is diverted to the systemic circulation, bypassing the liver, or there is increased production of ammonia due to an infection with certain microorganisms. Ammonia is a potent neurotoxin.

Ammonia is a potent neurotoxin, and elevated levels in the blood can cause neurological signs and symptoms that may be acute or chronic, depending on the underlying abnormality.