Small intestinal bacterial overgrowth(SIBO) is commonly found in people with IBS. The small intestine houses a miniscule number of bacteria when compared to the colon. When bacteria overgrow in the small intestine, it can cause symptoms of IBS. This includes:
- Nausea
- Gas/bloating
- Diarrhea
- Malnutrition
- Weight loss
- Hormonal imbalance
- Mood/anxiety disorders
- Fatigue
Ironically, the small intestine gets exposed to a higher amount of bile than the colon. Bile gets secreted in to the duodenum where it aids in the digestion and absorption of fats. By the time bile reaches the colon, 95% of the bile acids are reabsorbed and sent back to the liver for recycling.
Maybe not so ironically, bile has many effects that prevent SIBO. In this blog, we’ll cover the primary ways that optimizing bile can prevent and reverse SIBO.
1)Bile acids are directly antimicrobial(1)
The primary role of bile in the gut is the emulsification of fats/lipids. You see emulsification every day when you wash your hands with soap.
Emulsifiers such as soap and bile are ampiphatic. This means they have one side that loves water and one side that loves lipids. During emulsification, detergents such as bile separate large fat globules in to tiny emulsion droplets.
With soap, the goal is to break them up so they are taken away with water you rinse with. With bile, the goal is to break them up so fat digesting enzymes can access them better and break up the globule.
The antimicrobial effect of bile is due to this detergent-like effect on cell membranes. All cell membranes consist of a lipid bi-layer and bile can disturb this bi-layer. When this bi-layer gets disturbed, bad things happen. Fortunately your cells have bile acid transporters that prevent damage to them.
The bacteria inhabiting your small intestine aren’t so lucky. In the same way that washing your hands washes bacteria away, bile keeps bacterial counts in the small intestine low.
2)Bile causes the secretion of antimicrobial peptides in the ileum(1)
The ileum is the part of the small intestine located closest to the colon. Since the colon contains the highest concentration of bacteria in the gut, there needs to be a way to prevent bacteria from moving from the colon to the ileum.
When bile acids enter the ileum, they bind to a receptor known as the farnesoid X receptor(FXR). FXR does a few things and is a primary player in the recycling of bile acids. One of the other roles FXR plays is in the secretion of antimicrobial peptides.
FXR is expressed throughout the gut, but primarily in the ileum. This allows most bile acids to flow through the entire small intestine before reabsorption.
When bile acids bind to FXR in the ileum, antimicrobial proteins get secreted to prevent bacterial growth. Unlike the direct effect of bile acids, this is not selective.
This means that when bile acids bind to FXR, it prevents all bacteria from growing. This includes commensals. This is an important distinction because commensals are far more likely to overgrow in the ileum than pathogens.
3)Bile seals up a “leaky gut”
Bile acids also induce the expression of tight junction proteins through binding to the G-coupled protein receptor(TGR5)(2). FXR may also contribute to this effect either directly and/or indirectly(3).
Additionally, some bacteria in the gut convert primary bile acids in to secondary bile acids. The secondary bile acids activate the pregnane X receptor(PXR). This happens everywhere, but mostly in the colon since most commensal bacteria live there.
PXR has also been identified as a way that commensal bacteria communicate with you. Specifically, commensal bacteria convert tryptophan to a metabolite called indole-3 propionic acid(4, 5).
This metabolite increases tight junction protein synthesis. In layman’s terms, it seals up a leaky gut.
4)Bile contains(6) and causes the secretion of intestinal alkaline phosphatase(7)
Alkaline phosphatase is an enzyme secreted by the liver, gut, bone, and a few other organs. Recent research has identified intestinal alkaline phosphatase(IAP) as a major player in regulating the gut(8). Coupled with PXR, it may be one of the biggest factors in gut health.
Lipopolysaccharide(LPS) is a component of the cell wall of gram-negative bacteria. The immune system recognizes it and causes inflammation in the gut. This happens when LPS binds to something called the toll-like receptor 4(TLR4). Alkaline phosphatase changes LPS, making it unrecognizable to the immune system. And since it’s located right next to TLR-4, it’s a powerful modulator of inflammation.
Another way IAP promotes gut health is by regulating pH and the growth of commensal bacteria. To keep this blog under 5000 words, I’ll dig deeper in to how this works in a future blog. A little teaser…IAP can protect against antibiotic-induced pathogen overgrowth.
5)Bile decreases motility in the small intestine(9)
People with SIBO have altered motility. Motility refers to the rhythmic muscular contractions that cause peristalsis. These contractions move the contents of the gut towards and out of the anus.
The importance of proper motility in SIBO can’t be overstated. People with altered motility can have opposing symptoms in SIBO. People with fast motility will present with diarrhea. People with slow motility present with constipation.
In the small intestine, bile acids bind to TGR5 and reduce motility. This gives digestive enzymes more time to digest and absorb your food. This also reduces the amount of undigested food in your feces and reduces diarrhea.
6)Bile increases motility in the colon(10, 11, 12)
Bile acids have opposing effects on motility in the colon via the same receptor. When bile acids bind to TGR5 in the colon, motility increases. Therefore, this effect can prevent constipation.
One could also make the case that this could contribute to diarrhea. However, binding to TGR5 also regulates electrolyte and water absorption in the colon. This, in effect, reduces the risk for diarrhea.
An interesting finding in studies with mice is that TGR5 is absolutely necessary for proper defecation(11). Mice that do not have TGR5 have slower transit times(1.4x slower) and defecate 2.6x less than mice with TGR5. Data in humans is absent.
7)Bile regulates the migrating motor complex(12, 13, 14)
You’ve experienced the migrating motor complex before and never knew it. Do you know that growling you experience when you haven’t eaten in a while? That’s not your body telling you you’re hungry; that’s the migrating motor complex.
When you eat, peristalsis helps move your food through the gut to promote digestion and absorption of nutrients. These are considered digestive periods.
During inter-digestive periods, another process unfolds called the migrating motor complex. The migrating motor complex functions as the housekeeping system of your digestive tract.
After you’ve fasted for an extended period of time(5-11 hours), the migrating motor complex(MMC) cleans out debris in your gut. Digestive enzymes get secreted and waves of peristalsis move debris and bacteria towards the colon.
A malfunctioning migrating motor complex predisposes to the growth of bacteria in the small intestine(15, 16, 17). Bile plays a large role in both motility of the MMC as well as sweeping away bacteria that may begin to grow. It may even be involved in initiating the MMC(12).
Recall from above that bile acids bind to FXR in the ileum. Not only does this cause the release of antimicrobial peptides in the ileum, it recycles bile acids. Binding to TGR5 also causes the gallbladder to fill with bile for another round of the MMC.
8)Bile triggers anti-inflammatory genes(18, 12, 5)
When bile acids bind to FXR and TGR5, they block inflammation by inhibiting nuclear factor kappa beta(NF-kB). While this is great, it’s important to note that bile acids can also have a pro-inflammatory effect.
Water soluble bile acids are anti-inflammatory because they bind to receptors on cells. This changes gene expression which is good. Fat soluble bile acids can just enter cells and cause cell death. This effect is regulated by your microbiome and is not good.
Other receptors are also important for the anti-inflammatory effects of bile acids. Lithocholic acid(LCA), a liver toxic secondary bile acid, requires detoxification before getting sent to the liver. PXR starts this process.(19).
Anytime a ligand binds to PXR, including LCA, it blocks NF-kB. LCA also binds to the vitamin D receptor(VDR) and causes the same effect(20).
9)Bile promotes commensal bacteria and keeps them where they should be
Bile has been a component of the animal digestive tract forever. Because of this, human commensals that live in the small intestine have adapted genes that promote bile resistance(21, 22). This gives them a competitive edge over pathogens that compete for nutrients.
Since bile is antibacterial through its detergent-like effects, bacteria that aren’t bile resistant can’t colonize the small intestine. Unless, of course, the host isn’t producing enough bile. Keep in mind that some pathogens are also bile resistant so it’s not all rainbows and lollipops.
In the ileum, bile resistance isn’t necessarily a good thing. The ileum is an area ripe for over-colonization of commensals due to its proximity to the colon. In this area, bile resistance is overcome through the release of antimicrobial peptides by enterocytes. This happens when bile acids bind to FXR.
Thus, the overall effect of bile acids is to provide an environment where commensals have a competitive advantage over pathogens. At the same time, bile must keep commensals in check and prevent them from overgrowing in the ileum.
10)Bile is required for vitamin A absorption which optimizes all the above
Throughout this blog I’ve discussed a bunch of somewhat complex topics. You’ve already heard about VDR, but FXR and PXR are something you’ve just become aware of. Well, it’s time to learn about another “XR”…RXR.
RXR refers to the retinoid x receptor. The retinoid x receptor does so many things that we’ll only focus on one thing here. RXR makes the other “XRs” work better.
To work, VDR, PXR, and FXR bind to RXR to form something called a heterodimer. A heterodimer gets formed when two large molecules bind together. When RXR binds to any of the above, it forms a super receptor.
Note: In this image, the liver x receptor(LXR) is used. It’s the same process for all partners
When a ligand binds to PXR, it causes genetic expression of that receptors target genes. For example, when LCA binds to PXR, you get a certain level of expression of the genes that process LCA. If PXR forms a heterodimer with RXR and the ligand for RXR is bound to it, you get greater levels of expression of those genes.
It shouldn’t surprise you that the natural ligand for the retinoid x receptors is retinol, a form of vitamin A, specifically, 9-cis retinoic acid. Other receptors that form a heterodimer with RXR include the thyroid receptor and liver x receptor.
This means that adequate vitamin A intake optimizes all the processes regulated by these receptors. Conversely, inadequate vitamin A intake can make these processes run poorly.
Now, when we talk about vitamin A, we’re not just talking about any form of vitamin A. Retinol, the form found in animal products, is the form we’re looking for. Pro-vitamin A, which come from plant sources, requires conversion to retinol to activate RXR. In some people, including myself, this conversion is sluggish.
Since vitamin A is fat soluble, bile is required to bring it in to cells. With inadequate bile, you can’t absorb vitamin A from food or supplements. This spells bad news for people who have SIBO.
Conclusion
Proper bile output is important for preventing SIBO. Bile:
- Aids in fat/fat soluble vitamin digestion and absorption
- Is antimicrobial
- Regulates the microbiome and gut environment,
- Has anti-inflammatory effects
The ability of bile to promote the growth of commensal bacteria while keeping them where they should be is important to prevent and reverse SIBO. It also maintains the gut in a way that prevents pathogenic infection and leaky gut.
You can manage bile output and the content of bile via lifestyle modification. It’s tempting to take ox bile supplements but no ideal. If you choose to, it should be done for short periods of time and in the face of a nutritionally replete diet. The goal with its use should be to improve nutrient deficiencies quickly so you can get to work on your own bile production.
The use of ox bile is not without its drawbacks. Bile has great effects in the small intestine and colon but can cause problems in the stomach. Another issue is that you must first increase receptors that handle bile. Not doing this can can damage the gut.
In future blogs we’ll take a look at ways that modifying your lifestyle can improve your bile.
Question or comment? Hate my writing or love it? Is this stuff too complex? Leave a note in the comment section, I’d love to hear from you.
Great article!
Any suggestions on dealing with acalculous biliary dyskinesia? No pain or stones but hida scan of 6%. I am currently taking ox bile but your comments at the end about having the receptors concern me.
As you stated bile is so important to keeping bacteria etc in check. I have had pretty much every gut problem since this gallbladder problem started.
I still have my gallbladder.
Of course I can’t give you advice, but in that situation I would hit the low hanging fruit. Exercise, meal timing, and stress management. Not sure how you got here but if you could tell me more about your lifestyle I could probably nudge you in the right direction. What and when do you typically eat? As for increasing those receptors, I have some stuff on that coming up soon. Join the facebook group, I’m going to post more specific dietary recs in there in the coming weeks. Just gotta cross the t’s and dot the i’s. Don’t want to give out bad advice.
Looking forward to the next blog on optimizing bile production and receptor activity!
How does one increase receptors to handle bile? So that it’s not damaging to the gut….
I don’t think there’s a clear answer to that. Having a proper cortisol rhythm is likely important, as is making sure the ileum is not damaged.
You don’t know how to do it, yet above you state how important it is to do so?
Well, you asked — I hate your writing.
I don’t know how to increase bile acid receptors, but that has nothing to do with this blog post. This post is about increasing bile flow, not increasing bile acid receptors. This person is asking a question not addressed in this blog because it’s not something one cannot currently address outside of the 2 things I posted. There are ways to increase bile flow, but that’s not what she asked.
It’s unfortunate that you feel the need to be negative, but fortunately that’s your problem and not mine.
I have been following a healthy no gluten no dairy diet for a couple of yrs since i got this gb diagnosis. Taking supplements to support bile flow such as ox bile, digestive enzymes, milk thistle , beet root and dandilion, etc I am always on a quest to get to the root cause of why a gallbladder would suddenly (or gradually) lose its ejection capabilities barring no other obvious reasons. Ie. gallstones or pain so when i saw your article i was interested to hear more . I have not had much help from gastro’s on how to manage this.
This past yr i have had diagnosis of sibo, h pylori and blastocystis! So am currently working to rebuild gut.
Wow, doesn’t sound like much fun. The gallbladder is a funky organ. Are you familiar with the migrating motor complex? That’s something I feel plays a pretty big role in gallbladder motility. Another is the contents in bile and what gets done to them in the gut by bacteria. I think this may be something that’s an issue with you with the dx of SIBO, H. Pylori, and blastocystis. Bacteria in the gut deconjugate bile acids and bilirubin which may have an impact on bile signaling. I’ll be hitting upon these things soon. Here’s an interesting finding you might like to take a look at. I posted a blog on bilirubin a couple of weeks ago you may want to check out if you haven’t yet.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770027/
my teen boy has had undiagnosed gut probs all his life. Ended up with Sibo…which was treated by herbalist. The herbals got rid of reflux..but without oxbile he has nausea, mental health problems, food intollerances and chronic fatigue. Whilst taking oxbile at ever meal virtually eliminates all of the above. tried doing 3 months on and then off it..but horrible symptoms always return.
Dr. Eric berg on you tube has a great video on bad fat like corn soy and grape oils .bad fats are endotoxins for all your body cells.
He also has other videos on bile acids too.
In my understanding you have to eat clean keto . Remove toxins from your diet .
It can not be said enough to change your life style ,reducing stress factors of all kinds including from food toxins ,carbs and be ware of what you cook in microwaves Teflon pans and food store in plastics.
Really the list can go on .
To make it easier read food labels , eat keto don’t eat food from a box eat like you in live in the wild.
Love your veggies
And drink the crap out of water drink it through out day . I would suggest drinking at least 2 liters of water a day when you are not very active . Bile is also made of a lot water too. Remember your body is about 75% to 85% water depending on how dehydrated you are.
If you have not tried a liver flush I will attest to it successfully helping to flush out the old hard bile sludge and stones.
Hilda Clarks book “how to cure all cancers” is beautifully deep and honest book about are environment food and many other thangs . She will prove detailed info on how to flush your liver . Follow the flush instructions to the “T” do the parasite program it is a must !
I wish everyone reading this the best of life .
The Author of this blog is a treasure . My hat off to you and my shirt off my back if you needed it 😁
Thank you .
Hello, great article very informative. With that being said I have sibo that The deconjugates/alters my bile flow thus not allowing fat absorption and chronic diarrhea, I’ve tried things like ox bile to help but it just made things worse. Any idea of what’s going on?
Hi,
Been taking ox bile for few days with an unaltered diet (to see it effect) and I can say that it does decrease small intestine motility as it has made me more constipated (all other things being the same: diet, physical activity). I upped the dose once and it resulted in loose stools (probably due to the overflow into the colon).
Am suffering from SIBO C. Long walks do help but am at the very limit of whats physically possible.
Today tried ox bile on empty stomach (for its antimicrobial affect) but that seems to be getting me a reflux (thought as it alkalizing it might promote motilin and hence MMC) so that doesn’t seems to be a solution either.
Any ideas/guidance would be greatly appreciated.
Thx for putting up this blog and ur twitter handle.
Abhi.
Hey Abhi,
Check out my blogs on circadian rhythms, that goes over the circadian aspect of digestion which is very important because it regulates bile flow as well as colonic motility and other factors.
Good luck and thanks for reading!
Dave
Hi abhi r u from india how did the sibo c start and how is it progressing now as iam also a sufferer of sibo c from india would like to get in contact with u
@Dineshreddy123 Yeah buddy, u can call me at : nine eight seven six one six five three five two.
@Cincodum I’m not on Facebook what should I do to have access to ur article on improving bile acid.
For me bile supplementation (500mg) doesn’t has any positive effect, a slight increase in dose (750) gives cramps n diarrhea.
I remember hearing/reading somewhere that bile supplementation should be avoided with methane present SIBO. Is this true, and why? Because the bile can be constipating?
I have suspect sibo d along with pretty severe ibs d which do go hand in hand I believe. with the fact that I have frequent diarrhea and rapid transit . I would be hesitant to take ox bile and have been told and researched that welchol which is a bile acid absorbent0 could be very helpful. which is confusing ..it apparently slows down motility and also absorbs the toxins in the gut and colon/. does welchol initially absorb bile and then force the body to produce bile and therefore helpful in this way/
I am not familiar with Welchol so I don’t really have any idea. 100% of the time, I tell people to address their lifestyle first because your lifestyle regulates digestion via circadian rhythms and no matter what you do, if you’re telling your body to do the wrong things it’s really only responding to the information you’re giving it. After that, if someone still has issues we can look to see what may be causing them. But there’s no point in dropping single mechanism supplements or drugs until you know if your issue is caused by something you’re doing rather than something that happened to you. You can check our a blog I did on this topic here:
https://hackyourgut.com/2017/06/26/the-circadian-influence-on-gut-health-and-disease/
If video is more you thing you can check this out:
https://hackyourgut.com/2017/05/01/the-importance-of-circadian-rhythms-in-gut-health/
Bile is both directly and indirectly regulated by circadian rhythms. It’s dependent on light exposure via the master clock which regulates the cholesterol rhythm(Bile is made out of cholesterol) and it’s dependent on the feeding/fasting cycle and meal frequency. Most people do all 3 of these things wrong, and it becomes a bigger issue as you get older.
What about replacing bile with Tudca if you have no gallbladder?
You could do that, but I’m not sure it’s necessary and having bile in the stomach may not be a great idea as it may cause gastritis if used long term.
Great article!Waiting for more!
Thanks for reading!
Do you have an article or suggestions for people who have had their gallbladder removed and everything goes right through them immediately or within an hour? Dr recommends Welchol or Colestyramine which are cholesterol meds but act as bile acid sequestrants and I would rather take something more natural such as ox bile but have read many conflicting articles. Any thoughts, ideas would be appreciated. Thanks!
I’m not a fan of long term ox bile, and it would have the opposite effect of a bile acid sequestrant. At the very least you should increase physical activity which I wrote about here:
https://hackyourgut.com/2017/06/10/want-to-increase-bile-output-this-is-your-first-step/
It also may be helpful to tinker with fat and fiber intake, which would require changing things and paying attention to how you respond.
Finally, bile is heavily circadian so you should be optimizing your circadian rhythms. I have a program that helps you do that here:
https://hackyourgut.com/circadian-retraining-program/
In additions, I’m not sure your issue is simply a gallbladder/bile issue, so that program will help with digestion beyond gallbladder issues.
Let me know if you have any more questions and thanks for reading!
Great article!
“Another issue is that you must first increase receptors that handle bile.”
How do you increase these receptors?
“Water soluble bile acids are anti-inflammatory because they bind to receptors on cells. This changes gene expression which is good. Fat soluble bile acids can just enter cells and cause cell death.”
How do you avoid fat soluble bile acids? How do you avoid a pro-inflammatory effect?
Hello Michael,
I think good bile flow is probably your best bet for increasing bile acid receptors in the ileum. Optimizing your circadian rhythms, regular physical activity, decreasing gut inflammation, and maintaining healthy blood glucose levels are all the primary targets for that.
You can’t avoid fat soluble bile acids, that is primarily mediated by the microbiome. Same ways to approach it as above.
Any thoughts on olive oil’s ability to increase bile production? I read it somewhere (I forget where), but haven’t seen much on the topic.
Negligible if at all.
I may have bile reflux, but I definitely have SIBO. My GI wants to prescribe me a bile binder. Now I’m scared! I hope it’s okay to take them!
Targeted use of bile acid sequestrants can definitely be useful if you have problems with bile.
Can a person with SIBO take bile salts if their current production of bile is low? Thanks
They can, but I wouldn’t do it without being under the care of a practitioner. Bile shouldn’t enter the stomach and there are likely negative consequences to doing this long term.
Thank you for commenting. What about taking a supplement like TUDCA which helps the body produce more bile naturally?
TUDCA is a bile acid so not a fan of long term use.
Thank you
Thank you for the comprehensive article. Biggest piece of research on low bile salts and SIBO that I have read. Just discovered your site. Will be mining it. Can you link me to the area that would indicate your suggestions for raising level of bile salts naturally?
Why isn’t anyone talking about Bitters? They stimulate bile flow. I’m not sure that humans should be ingesting bile orally.
They shouldn’t be ingesting bile orally, and we don’t recommend people do that.
Bile homeostasis is complex, and bitters can be useful. But if the problem is poor bile synthesis, bitters won’t be effective. Bitters stimulate gallbladder contraction, I’m aware of no data showing they stimulate synthesis.
And if the problem is poor bile recycling or gallstones, bitters could make the problem worse.
Generally speaking, we recommend people consume bitter tasting foods as a general practice. Depending on the situation, supplementing bitters may be useful as a short term approach provided the root cause is none of the things mentioned above.
There are herbs that help with bile flow, but it’s advisable to work with a medical herbalist, just in case there might be gall bladder problems or stones, in which case, stimulating the gall bladder could produce unwanted symptoms if something was going on there unknown.
The herbs obviously would have stronger more medicinal effects than foods, but there are foods also.
Also bear in mind that some herbs (like Dandelion Root) have laxative effects.
But there are quite a few “cholagogues”. And there are also some “bitters” with milder action.
Hi! Thanks so much for the informative post. Can ox-bile give die off symptoms? I started taking it 3 days ago and I feel like my head is in a major fog like super allergies galore! Could it be related to taking ox bile from your experience?
It could be, but it could also just be a bad reaction to the ox bile. I find that people commonly assume that a negative reaction to something like ox bile is die off. But, we’re really not supposed to have a lot of bile in our stomach, so it could simply be a bad reaction.