Butyrate and Constipation

I have been excited about butyrate because rat studies showed that it increased the motility of the colon (please let’s not dwell much too long on the fact I’m reduced to rat status and writing about constipation).  I am going to summarize and explain an abstract to a study, from which the following quote is taken:

“Little is known about the environmental and nutritional regulation of the enteric nervous system (ENS), which controls gastrointestinal motility. Short-chain fatty acids (SCFAs) such as butyrate regulate colonic mucosa homeostasis and can modulate neuronal excitability. We investigated their effects on the ENS and colonic motility.” 

~  from Gastroenterology,  2010, “Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.”  Emphasis was mine.

Aside:  Please note that I am probably a fool and excited about nothing, but it is a path worth exploring for my slow transit constipation.  Also note, I do my best to simplify studies and concepts, some of which are difficult for my basic molecular biology background.  My husband, being an exceptionally logical and fact oriented doctor, hates it when I do this.  Big time scowls.  He is right, sometimes the explanations become kind of inaccurate.  So I will do the best I can.  If you have any questions or note any errors, I would like to know.  Gaps in my understanding will be bridged this way.  And one last note, don’t use my blog stuff to cause any harm to yourself.  Please.  See your doctor.

What did these researchers do? 

  1. Fed rats a resistant starch diet.  (I will write a resistant starch post soon.  Soon is always relative.)
  2. Inserted short chain fatty acids (i.e. butyrate) into rats’ cecums (a part of their colons).  (I only have an abstract so we are left to our imaginations for this lovely process.)
  3. Applied butyrate to some “free-standing” cultures of enteric nervous system cells in a “test tube.”
  4. In the “test tube” cells, they examined how the cell “looked”–its “phenotype.”  What kind of receptors did the nervous system cells have on their outer membranes?  What kind of proteins are expressed?  Knowing this kind of information helps us to know what the cell is capable of responding to and what substances the cell makes.  Special antibodies that will seek out these known proteins and receptors on the cells are used.   Researchers also used polymerase chain reaction (PCR), a way to amplify and increase certain material.  Specifically, these researchers looked for antibodies to Hu, choline acetyltransferase (ChAT), and nitric oxide synthase (NOS).  If you refer back to “Changes in Severe, Chronic Constipation,”  you will see a couple of these discussed:  Less neurons immunoreactive for ChAT and more neurons immunoreactive for NOS.  They also proceeded to analyze signaling pathways using various tests.
  5. Observed the motility of the colon both in the rat and outside the rat.

What were the results?

  1. Resistant starch diet (which increases butyrate) and butyrate (but NOT acetate and propionate, other short chain fatty acids made from resistant starch by the colon’s bacteria) both:
      A.  Increased the ChAT neurons, these are the ones partly responsible for increasing peristalsis.  Neurons with ChAT should make more acetylcholine, the neurotransmitter that encourages the bowel to move forward and empty.
      B.  Did not alter the NOS neurons’ proportion and number.  NOS would bring about nitric oxide, which slows down the bowel’s movements.  It makes the bowel relax rather than move.
  2. Bowel neurons have a transporter called monocarboxylate transporter 2 (MCT2), which helps bring butyrate into the colon cell after the bacteria graciously make it.  Well, the researchers were able to “stop” these transporters so butyrate wouldn’t move into the cell so much.  By stopping the MCT2 transporters, the increase in ChAT neurons–and therefore neurons that would increase colon motility–was halted.
  3.  Butyrate increased histone H3 acetylation in enteric neurons.  When DNA is acetylated, it allows the DNA to be transcribed.  So butyrate alters the actual genetic expression of cells.
  4. Resistant starch diet increased colonic transit.
  5. Ex vivo it was noted that butyrate increased the circular muscles contraction when exposed to acetylcholine.

Their Conclusion

“Butyrate or histone deacetylase inhibitors might be used, along with nutritional approaches, to treat various gastrointestinal motility disorders associated with inhibition of colonic transit.”  And that’s as far as I’ve seen it up to this post.  I’ll keep looking.

My Conclusion

I’m not trying to live forever.  I don’t have cancer yet.  I’m eons away from a stroke.  But my gut has a mind of its own.  In addition to more information on butyrate (and resistant starch), I need to explore the outcomes of slow transit constipation in 80 year-old women.  Do they have a study on that?  Right now, things are tolerable with all the changes I’ve made the last 18 months or so of my life, but what happens later?  Or when the magnesium stops working again?  Anyhow, here are my closing thoughts:

  1. Butyrate is made in the gut and absorbed by the gut.  The gut has been my constant, lifelong problem.
  2. Butyrate may affect the immune system and decrease inflammation.  We have studies supporting food intolerances causing severe, chronic constipation and these studies document subtle inflammatory changes in the mucosa.
  3. Butyrate may affect the nervous system through modulation of gene expression.  We know the enteric nervous system is messed up in slow transit constipation.
  4. Butyrate may stimulate the contractile activity of the colon and accelerate GI transit.  We know slow transit constipation has a reduction in high amplitude propagating contractions and a disruption of the coordinated peristaltic activity.
  5. Butyrate is increased by eating resistant starch, a type of “fiber.”  (This is a bit confusing, but I will clarify later.  Resistant starch would be high in diets rich in lentils, beans, tubers, etc.  Please see Butyrate Series, Part 6 for a better, more thorough explanation)  Fiber has long been recommended for constipation.  Perhaps it’s not the fiber.  It could be the fiber.  Or it could be a rich bacterial population capable of making more butyrate for an individual.
  6. Butyrate has been shown to possibly decrease colon cancer.  Colon cancer is higher in patients with chronic constipation (Chronic Constipation Linked To Increased Risk of Colorectal Cancer–summary article from Science Daily).

And finally, I’ll leave you with this quote:

If the promising results by Soret et al [the paper whose abstract I summarized and explained above] can be confirmed and expanded by controlled therapeutic trials, then butyrate-generating foods might become an effective and simple option to prevent or treat functional gut disorders via modulation of enteric neuroplasticity.” (2–a very good little commentary to read!)

Terri

Butyrate Series Page

Sources:

1.  Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, Neunlist M.  Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.  Gastroenterology. 2010 May;138(5):1772-82.  Sadly, abstract only:  http://www.ncbi.nlm.nih.gov/pubmed/20152836

2.  de Giorio R, Blandizzi C.  Targeting Enteric Neuroplasticity:  Diet and Bugs as New Key Factors.  Gastroenterology.  2010 May; 138(5):1663-1666.

Also, if you will please see “Why Does My Gut Defy Gravity:  Changes in Severe, Chronic Constipation” and But What Causes All of Those Changes Found in Chronic, Severe Constipation?and “Cow’s Milk and Refractory Constipation”   then you can find further information plus sources for that information and information mentioned above.

Thanks,

Terri

I also have run a whole series on butyrate.  I need to come back and link eventually; the WordPress blogging platform used to have a feature to do that but not now.  If you look under GI Tracts Defies Gravity page, there are links there to the series pieces.

16 thoughts on “Butyrate and Constipation

      1. Holistic Wayfarer

        I wouldn’t have it any other way, though (rather, because) I’ve taught in the public schools. My second article has just gone out globally in this publication:

        http://homeschoolenrichment.com/

        In fact, I see that the issue with the girl on the cover is the one with my first article on achievement. On the upper left of the cover, you’ll see “Climbing High,” the title. =)

    1. thehomeschoolingdoctor Post author

      Yes. “A unique feature of milk fat from ruminant animals is the presence of butyric acid….Bovine milk fat contains from 7.5 to 13.0 mol/100 mol butyric acid. Because dibutyrylacylglycerols are present in trace amounts only, this means that about one third of milk fat triacylglycerols contain one molecule of butyrate. On ingestion, lipase-mediated hydrolysis of butyrate commences in the stomach and will be complete on reaching the proximal small intestine. Liberated butyrate is absorbed from the intestinal lumen to the enterocytes; it then passes directly to the portal circulation for transport to the liver where most is metabolized (Parodi 1996). Can butyrate from this source or together with colonic generated butyrate, as a result of a high fiber diet, modulate carcinogenesis at sites other than the colon? The evidence is meager…” (Cow’s Milk Fat Components as Potential Anticarcinogenic Agents)

      Reply
  1. Pingback: Butyrate Series, Part 2 | The HSD

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  4. poetrydude66

    Have you tried something like polydextrose? As I understand it most of the caloric value of this starch is not metabolized and remains in the gut. It should increase activity of bacteria and might lower transit time through the gut. Some people complain of gas, and some people claim that effect goes away if you introduce polydextrose slowly.

    In any case, polydextrose is cheap and plentiful industrially produced resistant starch, and therefore you at least have a basis for measuring it and testing with it, cost effectively.

    It’s difficult at best to know how much butyrate you are producing, and even if you had a pharmaceutically pure source for it, my guess it it gets metabolized to ketones pretty rapidly. What really benefits your gut is feeding the good bacteria, so it’s a question of testing different kinds of resistant starches to see which produce the effects you want.

    Reply
    1. thehomeschoolingdoctor Post author

      No. At this point I have not tried polydextrose. I was having good success with oral butyrate (don’t ask me how this worked as an oral supplement–at this point I can’t explain it) which I then transitioned over to resistant starch in the form of green bananas; cold, leftover-from-my-family’s-dinner potatoes; some cold leftover rice; and potato starch mixed in water. As things were going very well with this prior to my becoming pregnant, I continued this experiment–until I got too “sick” to want to eat any of that or anything else. And all I want to do is make it off the couch. 🙂

      I was not under the impression that polydextrose (which for those reading comments– is glucose/sorbitol/citric acid synthetically combined and often used in processed foods to replace sugar and fat, allowing for less calories without sacrifice of taste and texture. It is also available as a supplement.) is a resistant starch. I would categorize it as a soluble fiber–which will have some effects of resistant starch–but not completely. I try not to eat processed foods so I would not eat it this way. Also, I try to obtain all nutrients I can as whole foods, unless I just need more than I can get to heal/be stable (such as in vitamin D or magnesium or my butyrate trial). As a supplement, I may consider using polydextrose as I would consider FOS or inulin. If I’m not meeting my goals, it may be something to try. However, I’m not sure I see the advantage of it over FOS or inulin. Do you have an opinion on this? Have you tried polydextrose?

      I agree that it is difficult to know how much butyrate you’re producing, for sure! And I see your point about quantification of polydextrose (compared to the variability of resistant starch). For what it’s worth, I would like to point out that short chain fatty acids (SCFA), like butyrate, do not get metabolized into ketones. SCFA, however, as you suggest, are very quickly absorbed usually from the GI tract–just not to be converted to ketones.

      Feeding the bacteria is very important, which the role of fiber and resistant starch do well, but we need to be sure that we are feeding and increasing SCFA/butyrogenic bacteria. So I guess we’d need to know the effect of polydextrose specifically on the butyrate-producing bacteria/production of butyrate. Is there a study like that for polydextrose? Of course, like you say, testing it on ourselves is all that it comes down to in the end.

      Thanks for the comment. I appreciate it. I had not read much on polydextrose, so it was nice to be able to do that a tad. Take care.

      Reply
      1. poetrydude66

        I have not experimented with polydextrose yet. I have been looking for ways to increase soluble fiber. I’m using chia seed in the morning (about three tablespoons) which I like because it holds water pretty well in its gel form and keeps me hydrated. I use grapefruit pectin as well (which tastes awful) but I’m currently just wanting to experiment widely and test.

        On butyrate, I only have read superficially, but typical references are like this one:

        https://ahdc.vet.cornell.edu/clinpath/modules/chem/BHB.htm

        which contains the comment “In ruminants, both NEFAs and volatile fatty acids produced from rumen metabolism can be used to form ketones. Proprionate, butyrate and acetate are volatile fatty acids that are produced by rumen fermentation. Of these, mainly butyrate is converted to BHB in the rumen epithelium and the liver.” Of course he is talking about ruminants not humans. And it is pretty difficult to find much discussion of butyrate in humans, because we don’t have the long lower intestine needed to produce a whole lot of it. But why would butyrate metabolize differently in humans, once it is somehow in the intestine?

      2. thehomeschoolingdoctor Post author

        Bingo!!!! Thanks for that link! I have visited that site before for butyrate, but I don’t think I saw this–or I forgot I saw this! I have been wanting to tie together coconut oil with its beta-hydroxybutyrate component (ketone) with butyrate. I googled something like that many times. Why wouldn’t they be interchangeable? I will check that out and see what I can understand better. Thank you! It may be a rumen study, but it was rat and pig studies that got me started on butyrate because like you say, hard to find much discussion of butyrate in humans. I will print it off and look forward to reading it!

        I have read a little on the differences between gorilla guts and human guts. I’m going to need to read a little more so I can be on the same page as you (thus the lack of reply on another comment you have made–sorry).

        I tried chia seed, but I didn’t see much difference for me. However, I do think that over the two years since I’ve started this, my GI tract environment has changed for the better. So I wonder if some things that I have tried in the past may work now when they wouldn’t have before. Not to mention, chia seed can make some good recipes. I have not heard of grapefruit pectin–must taste pretty bad for you to say that! If you try polydextrose, come back and let us know how it goes. It’s always the comments on blogs where you learn so much!

      3. poetrydude66

        You might find this blog post useful regarding gorillas:

        http://rawfoodsos.com/2010/03/18/what-is-the-optimal-diet-for-humans-part-2/

        So the long and short of it is that “In chimpanzees, gorillas, and orangutans, the colon is about two to three times the size of the small intestine. But in humans, those figures are reversed: the small intestine dominates, clocking in at over twice the size of the colon.”

        So a gorilla eats a ton of resistant starch, and has massive amounts of bacteria in its much longer colon, which then ferment the starch to butyrate and other short chain fatty acids. Some of that butyrate feeds the gut, but a lot of it goes to metabolism, to the liver, and creates ketones. So even though the perception is that the gorilla has a high carb diet, in fact the gorilla has a high fat diet! The key is that the carbs are converted into useful fats by the bacteria. But the gorilla is using primarily fats for metabolism.

        Humans don’t have much colon and therefore cannot ferment effectively. This is exactly where my knowledge ends. So how much butyrate can we actually produce? How much of that feeds colon cells, and how much escapes into the blood and gets used in metabolism?

      4. thehomeschoolingdoctor Post author

        Thank you for that!

        The quantitative amount of butyrate I can not supply you right now. However, the amount of butyrate production is highly person variable, depending on the foods they eat, the type of bacteria and quantity of those bacteria they have, and their transit time.

        I believe 70-90% is used by the colonocytes while the rest goes to the liver.

      5. poetrydude66

        Just a follow up on my previous post: my understanding is that an animal like a gorilla is able to convert large amounts of fiberous plants into short chain fatty acids in the lower intestine. Because the gorilla’s lower intestine is so much longer – as a percentage of body weight not just in absolute terms – than human lower intestines, they are able to produce very significant amounts of butyrate and other SCFAs and actually use those for metabolism. So we think of the gorilla as being a carbohydrate eating animal, when in fact most of their calories are coming from fats that their gut is creating from the plants. Yes, the butyrate is feeding colonic cells, but it is also rapidly absorbed into the system and metabolized to ketones.

        I thought MCT Oil was doing something very similar to this, and it bypassed the normal long chain fatty acid metabolism in favor of a shorter path to the liver that creates ketones as well.

        Now it’s an open question for human beings, if we create much smaller amounts of butyrate from resistant starch, how much of that is feeding our colon and how much of that is coming into metabolism and being used for energy?

      6. thehomeschoolingdoctor Post author

        Fascinating to read about the gorillas’ gut and how their consumption of fiber/RS is actually a mechanism for getting increased fat!

        I mentioned it in another response, but I’ll state it again because you never know what gets seen and doesn’t. I believe that 70-90% or our own butyrate production is to feed our own colonocytes, while the remaining heads to the liver.

        Two articles:
        1. This one briefly describes the effects of MCT in humans: http://jn.nutrition.org/content/132/3/329.full

        2. This one has nice a nice schematic graphic for butyrate metabolism (including a final pathway which could take it to a ketone): http://pathman.smpdb.ca/pathways/SMP00073/pathway?level=2

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