Microbiome - Butyrate - Inflammation

[LINE]

This is a good article describing what Alternative medicine calls "leaky gut". Personally, I find the term helpful in some ways (better understanding) but is deficient in offering better clues to what is going on.

The simplified version of the article is that are proteins that reside in the gut (and other tissues as well) that help form a solid surface. Cells are like pieces of a puzzle that lock into one another. If the cells cannot lock into one another, then gaps form in their junctions. If there junctions are not tight, then things leak out. Those things are not good things, so they cause more problems in the body. Specifically, inflammation is never never good.

https://www.nature.com/articles/s12276-018-0126-x

There are lots of things that cause the junctions to be loose including toxins, pathogens like bad bacteria or parasites, improper nutrients (there are some specific ones).

If the junctions are tight, then the body can produce butyrate and butyrate is a good thing, it heals. If the junctions are tight then inflammation is drastically reduced, that is a great thing!

There have many important studies released recently that show the gut is a center piece of many ME issues and there appears to be problems with not having enough healthy bacteria (actually specific classes of probiotics that cannot be obtained in typical probiotic blends).

I have a decent grasp of some of the other concepts if anyone has questions.

 

[Garz]

the problem i see with these kind of studies and part of the reason for the lack of actionability is that the direction of causation has not been rigorously established - while the papers strongly suggest or at least assume it has

for instance there are papers showing that diseases that cause malfunction of the microcirculation cause hypoxia and inflammation in the sensitive gut lining

such inflammation is then linked to dysbiosis and hyperpermeability

so did "CFS" - or whatever biological mechanisms are at the root of it - cause leaky gut - or did leaky gut cause CFS?

in reality these disease states likely have feedback loops - such that its more of a re-enforcing cycle than a linear causality - but still the chicken or the egg problem remains....

 

[godlovesatrier]

You should checkout the larozotide acetate thread/s. For something that heals tight junctions.

Alternatives are to eat a lot of prausnitzii foods like black eyed beans, butter beans, navy beans and kiwi fruit. That will increase your butyrate which will also heal your tight junctions. It's unclear if diet is enough tho if your repeatedly suffering from an intestinal wall breakdown. That is repair, heal, infected, breakdown in repeated cycles with viral reactivation for each.

 

[Wishful]

If the junctions are tight, then the body can produce butyrate

No, the body doesn't produce butyrate. Bacteria in the digestive tract produce butyrate, whether your junctions are tight or not. Bacteria-produced butyrate helps keep your intestinal cells healthy.

 

[LINE]

No, the body doesn't produce butyrate. Bacteria in the digestive tract produce butyrate, whether your junctions are tight or not. Bacteria-produced butyrate helps keep your intestinal cells healthy.

Thank you for your input. Yes, you are correct, the butyrate producing bacteria (f. prausnitzii etc.) do that but they cannot proliferate in a hostile environment (high ROS), that point was clarified in recent papers. The high ROS is being generated by inflammatory cytokines. Technically, butyrate would help modulate (and repair) the TJ thus allowing the butyrate producers to take hold. It is clear that the butyrate producers are anerobic and with the high presence of ROS, cannot take hold. https://pubmed.ncbi.nlm.nih.gov/29796620/

The way I read it, the situation becomes a double-edged sword, or which came first scenario. To me, it is obvious that there is immune activity that is creating all the chaos (ROS). Some suggest unwelcome microbes that triggers the immune response; however, environmental toxins can induce this as well.

As you know, ROS (and RNS) are very damaging molecules and downstream into metabolic pathways and perhaps the most damaging is the attack of mitochondria.

 

[godlovesatrier]

think you might be onto something with the high ROS btw, but I think it might just be due to viruses in the gut that cause the ROS in the first place, or bacteria of course. It's just a theory sadly but I experienced 90% for the first time in 8 years start of 2023, assume it was low to no viral load briefly in the GIT which meant no ROS, which meant very high butyrate production. I felt amazingly well compared to how I feel now.

 

[Wishful]

If the problem was as simple as high ROS from cytokines, I would expect that taking some antioxidants would reduce the symptoms. I haven't noticed any such reduction.

 

[Garz]

you can also supplement with butyrate - i have tried it - but found very little impact - which is what most of the studies on exogenous butyrate supplementation also find.
it just doesn't seem to do the same thing when you consume it - as when the bacteria are producing it - probably because of all the other things those bacteria would be doing and making if they were in fact present and metabolizing happily in the gut - things that do not happen and are not present if you just add the butyrate on top..

This fits with there being an upstream problem - rather than just not enough butyrate.

 

[Wishful]

it just doesn't seem to do the same thing when you consume it

It's possible that all the studies measure butyrate and effects, but the real factor is some chemical or other communication medium released by the bacteria while they're producing butyrate. It could even be something released when those bacteria die and break down. A correlation between butyrate and some effect does not prove that it's actually butyrate causing the effect.

 

[LINE]

think you might be onto something with the high ROS btw, but I think it might just be due to viruses in the gut that cause the ROS in the first place, or bacteria of course. It's just a theory sadly but I experienced 90% for the first time in 8 years start of 2023, assume it was low to no viral load briefly in the GIT which meant no ROS, which meant very high butyrate production. I felt amazingly well compared to how I feel now.

Yes, could be many types of pathogens. PubMed studies on this will test using a known toxin that can produce the same result. I will have some updates on my experiments soon.

 

[LINE]

If the problem was as simple as high ROS from cytokines, I would expect that taking some antioxidants would reduce the symptoms. I haven't noticed any such reduction.

Yes, your observations are correct as that has been my experiments hundreds of times. What the research indicates is the role of fatty acid metabolism on the tissue membrane. One article described the epithelial matrix in the GIT as being the most complicated. That makes sense to me. I have ongoing experiments that I will report on. So far, they are positive outcomes.

 

[LINE]

you can also supplement with butyrate - i have tried it - but found very little impact - which is what most of the studies on exogenous butyrate supplementation also find.
it just doesn't seem to do the same thing when you consume it - as when the bacteria are producing it - probably because of all the other things those bacteria would be doing and making if they were in fact present and metabolizing happily in the gut - things that do not happen and are not present if you just add the butyrate on top..

This fits with there being an upstream problem - rather than just not enough butyrate.

That was my experience multiple times, it never took hold. That is why I Iooked at trying to produce it within. I should have updates soon on my tests.

 

[LINE]

Some updates:

>The better my gut behaves, the better I feel. More energy, less brain fog, better mobility, less pain and anguish etc.

1. The tight junction proteins seem to be the center piece of the fiasco.

2. If the TJP are damaged, the gut cannot heal.

3. If the TJP are damaged, then naturally formed butyrate cannot be formed.

4. Antioxidants (tried a laundry list) can help reduce some of the damage, but do not actually heal TJP

5. Oral butyrate never really helped (tried regular butyrate and new forms tributrin).

6. I tracked all my notes on gut responses. Loose stool = inflammation, normal stools indicate a healthier
environment. That is how I gauge my tests.

7. Multiple (50 tests) using probiotics, ferments, different fibers have never worked.

8. Colostrum, Vit A, D can assist but do not heal the tissue.

9. Carnosine/Zinc, Zinc did not work.

10. Collagen (peptides) or broth offer some assistance but no cure.

12. Binders such as charcoal, clays etc. help (but not cure). These will sweep the toxins out which is important as toxins are known to impact TJP.

13. I did Ozone therapy via rectal insufflation which is known to activate several pathways, have direct killing of microbes and help build some beneficial bacteria - helpful but did not cure.

14. Multiple herbal formulas such as Traditional Chinese Medicine, ginger, turmeric, ashwagandha, South American herbs, lots of anti-biotics etc. did not cure it.

15. Likely missing the hundred other things I tried including acupuncture and many others.

16. Identifying inflammatory foods help in stopping the inflammatory process but did not cure.

 

[LINE]

My focus now is on fatty acid metabolism. FAM is a little complex since it involves a number of different pathways and nutrients. I have seen some results with Omega 3s and other good fats, but these require some nutrients that assist, and I think the types of fatty acids are important.

(Lipid metabolism and gut health were clearly correlated).

I got some of my information about this from reading PubMed studies on Cultured Ghee and the specific lipids that are found in this. Note that cultured ghee is different from just ghee. Ghee is clarified butter but has some different lipid complexes than say butter. FYI, butter contains natural butyrate but likely lower levels. . Ayurveda uses clarified ghee for gastrointestinal problems.

This research led me to lipid profiles found in other milk (besides cow). Although, I should mention that buttermilk (cow) has some unique lipids that indicate it could be helpful for the gut. I have read in the past that buttermilk was beneficial for the gut, the research seems to back that up.

I had trouble finding organic whole buttermilk, so I ended up at the Indian grocery store and found it (although not organic) and to my surprise, it also contains water buffalo milk. (yes, I drank it :>) ) Ialso bought water buffalo/cow butter.

 

[LINE]

Part II:

Not only did I venture to drink water buffalo/cow buttermilk, but I took some scoops of clarified ghee which was infused with spices known to curb inflammation such as turmeric, Ceylon cinnamon and others.

I also added some other oils that I have used in the past that produced some good results in the gut.

But IMO fats are not enough unless they are converted by other nutrients, here is what I know:
(perhaps that is why oral butyrate does not seem to work, as it needs other nutrients to metabolize).

1. Coenzyme A is a major enzyme that participates in FAM (fatty acid metabolism). I have known about Coenzyme A because I see benefits in the gut with pantothenic acid (Vitamin B5). My previous tests have always shown benefit when taking Pantothenic acid (PA). PA participates in FAM.

2. Choline is the same result as PA. Choline participates in FAM.

3. Carnitine is a big player in FAM. Of interest, lysine can create carnitine, my notes indicate when I took lysine, it showed up with good gut responses.

4. Various other nutrients are required which I get from a good vit/mineral supplement. Various b vitamins (B6 etc.), Vitamin C etc.

My theory is that correct fatty acid metabolism is key for the repair of TJPs. IMO, taking health fats is not enough and taking the correct fats seems to be important as well.

If the TJP are corrected, then the gut environment will produce the necessary environment to create a healthier microbiome thus producing beneficial molecules such as butyrate. As a side note, butyrate (and other SCFAs) has far reaching effects, they impact metabolic pathways, has been implicated in controlled Type 2 diabetes, blood pressure, cholesterol and I am sure countless other pathways.

 

[LINE]

Lastly. I have read many articles about the benefits of drinking milk from other animals (not just cows). I am not sure about Goat's milk, but Camel milk is known to have positive molecules that can assist the gut. I have not ventured into this arena as yet. If anyone wants the PubMed links for the specific biochemistry, let me know.

Phospholipids also seem beneficial to me. These are likely in the lipid family but have a different constitution. I take Sunflower Lecithin which is a phosphatidyl family (phosphatidylcholine etc.) Phospholipids make up much of the cell membranes. Cell membranes are damaged from oxidative stress.

 

[LINE]

Note that TJ are found in the gut, but they are found in other tissues. The brain uses TJ which lead me to the question of the neurological impact of ME - are the TJ also deficient in the brain which leads to brain fog, anxiety, memory issues, cognition?

 

[godlovesatrier]

Am currently on larozotide acetate and feeling pretty good. I could do a biomesight test next week and see if butyrate is high. It won't mean much but I can say emphatically that the amount of butyrate has been low overall the last 8 months, it was high march/april but I think that possibly due to high ROS it was supressed and never recovered. So am interested to see if low ROS and larozotide will increase it.

 

[Garz]

one thing you could experiment with that helped me more than anything else i had tried to that point is a ketogenic diet.

i was totally against this initially as i had been into sports nutrition all my life and did well on complex carbs. but once i got ill i had many gut symptoms and my systemic symptoms like pain and fatigue also increased with gut symptoms - which changed with what foods i ate.
my partner tried the ketogenic diet out of desperation - and went running 2miles within 1 week - and she had been as fatigued as i was until that point.
after seeing that i could not deny the benefits and decided to try it myself
i did not go as extreme as she did - but was also male and had more muscle mass so typically easier to get into ketosis

i believe it works by dramatically reducing the amount and type of bacteria in the gut, which in turn takes a large load off the immune system, 80% of which resides in and around the gut and is concerned with managing the contents - ie stuff from the outside world and the bacteria that grow on it.
so it results in less immune dysfunction / immune triggering inflammation and reduces overall symptoms significantly - in my partners case it was pretty much enough on its own to get her well enough to start work after 6 months

i mention it as - when you increased your fat intake you likely reduced your carb and fibre intake as an unintended consequence - and that may have brought the benefits you experience.

its a zero cost trial - just takes effort
i was fully against it but have changed to eating that way for the last 2 years - because it helped

 

[LINE]

Update:

I now have spent a great more time pouring through articles and trying some experiments, here is a short update:

1/ I modified my diet to more keto and found that was counterproductive for me. The saturated fats made me fill like I swallowed a car That could be an issue with my metabolism. My diet is pretty clean (no inflammatory foods)

2/ I switched Omega 3 fish oil to Krill oil. Although both contain Omega 3, Krill oil is different since it contains the Omega 3s as Phospholipids (PL). PL are the primary component of the cell membrane, so it would appear that this is a valid theory. I am testing at the moment.

3/ Cultured Ghee (3 days in). I did past experiments with just ghee, now testing cultured ghee. Ghee does have a different composition of fats that are reported as beneficial in PubMed articles.

4/ I am working on improving my fat metabolism with some key nutrients. There likely could be a break in that pathway thus not allowing the fats to be broken down and assimilated correctly.