Gut Microbiome - Editor's Choice

A few years ago, I was writing about how manipulation of the gut microbiome may likely alter (in a very good way) the course of many diseases associated with gut dysbiosis.

Dysbiosis is when the gut bacteria become unbalanced toward more pathogenic disease-promoting bacteria generally seen in sick people with a disease. This would include a rather lengthy list of ailments.

At the time, I concluded that the easiest, fastest, least expensive, and simplest way to prove or disprove this idea was to use a Fecal Microbiota Transplantation ("FMT") on people who have a disease that is well noted for having gut dysbiosis, such as Parkinson's disease.

FMT is when you take a stool transplant (poop) from a very healthy person and transplant it into the colon of a person with a disease and gut dysbiosis for the purpose of rebalancing the gut microbiome away from pathogenic bacteria toward health-promoting bacteria with the intent of improving the disease state.

FMT is already used for a small handful of diseases, such as the following :

1. Clostridium Difficile (C.Diff) - This is the #1 health issue FMT is used for.
2. Ulcerative Colitis
3. Crohn's Disease
4. Obesity
5. Autism
6. IBS [1]

I had to wait a couple of years for a study to complete regarding FMT and Parkinson's Disease (PD) in 2020. Another FMT/PD study completed this year in 2021 and the results, although both studies were small in the number of participants, showed very good benefit in both studies that suggested a greater than 50% reduction in test scores which mirrored a greater than 50% reduction in motor and non-motor symptoms that is better than any other currently available adjunctive treatment for PD has ever shown!

It is interesting to note that the participants in the study only got less than 2 ounces of the FMT (donor stool) mixed in a saline solution and delivered via colonoscopy to the colon, once, at the very beginning of the study, and this transplant showed continuous symptom and test score improvement right up to the end of the 12-week study!

Since FMT in the US is mainly only available for the six listed health issues above, it made me wonder if there is a way that we could somehow try to replicate the results of FMT on our own since nobody knows if or when FMT will come available for a multitude of applicable diseases. This search for such a path turned out to be more complicated than I had realized.

My initial thought is that perhaps with the right probiotics, we can add the needed bacteria to the gut to try and rebalance the gut microbiota toward health-promoting bacteria. I quickly learned that this was not a practical or feasible approach because the gut biome consists of approximately 100 trillion bacteria and a very diverse bacterial selection, while probiotics are generally only available in the billions of CFUs and are not diverse compared to the gut microbiota.

If a probiotic had 20 different species, it would be considered very diverse, whereas the gut microbiota consists of an estimated 300 to 500 different bacterial species! So probiotics are basically underpowered and insufficiently diverse to have the desired effect of completely rebalancing the whole gut microbiota. They can likely help, but not complete the job at hand. [2]

Then I thought, well, maybe the body actually has a way to generate the needed bacteria to rebalance the gut biome, but I did not find such a mechanism in any studies that I looked at.

I knew that the body had a way to let the pathogenic bacteria replicate at an increased rate via the anti-health vicious cycle of oxidative stress and inflammation that promote and feed off of each other and then further the advance and progression of ill health and disease and is reflected by gut dysbiosis. I had always wondered why there was not a Pro-Health repetitive cycle as a healthful counterbalance to the anti-health oxidative stress/inflammation cycle. I thought that if there were such a pro-health cycle that it would have been written about extensively and illustrated a long time ago, but I had never read of such a mechanism in the body and so I never gave it any more thought until recently when I saw the results of the FMT/PD studies.

After reading those two studies and their exceptional results, it got me to wondering about a potential pro-health repetitive cycle again.

Since FMT acts in the gut, I thought that if such a pro-health cycle exists, FMT suggests that it may exist in the gut. So I took the idea that oxidative stress and inflammation in their vicious cycle seemed to promote gut dysbiosis and increased imbalance of the gut toward pathogenic, disease-promoting bacteria, and I tried to look for some mechanism in the gut that could potentially promote the health-promoting bacteria in the gut.

What I found is the commonly referred to in studies, Short Chain Fatty Acids (SCFAs), of which there are three predominant ones called Acetate, Propionate, and Butyrate. Of these three, butyrate seemed to be the most studied and in studies was mainly noted for its usually anti-inflammatory activities, but that did not seem nearly enough to combat the anti-health oxidative stress/inflammatory cycle. But more importantly, where was the component that butyrate and the other two dominant SCFAs could feed off of in a repetitive pro-health cycle and, in turn, it could feed off of them to continue the cycle?

The Role of Melatonin in Gut Microbiota

So my search continued, and as many of you know, I have written extensively about melatonin.

Melatonin is generally present in my forethinking because of its importance throughout the body and in all of the body's organs. I remembered a statistic about melatonin that has always stuck in my mind because I felt it had very significant importance. This statistic says that melatonin is produced in the gut at 400 to 1,000 times the melatonin production in the pineal gland in the brain!  That has to be important for health!

Given that information, I started reading about melatonin and the gut microbiota. After reading a lot of studies, I was beginning to think that melatonin may be the missing component that could interact with SCFAs to form a pro-health repetitive cycle. So I started looking for studies about melatonin and SCFAs.

From the limited literature on this specific subject, I was able to find studies that showed that melatonin and SCFAs tend to decline with age in a similar way to the way age-related diseases increase with age, an interesting coincidence?

I also found that melatonin increases the bacteria in the gut that are needed for the production of SCFAs, and these bacteria are reduced in many disease states. In turn, SCFAs increase gut melatonin production and melatonin receptors in the gut, which are also reduced in the presence of disease.

Another important thing that melatonin does in the gut is activate PPAR-y or PPAR-gamma (PP-y), which increases insulin sensitivity, enhances glucose metabolism, and plays a significant role in metabolic function and energy homeostasis. It is a preeminent player in the gut biome, and the fact that one of the many things that melatonin does in the body is activate PP-y says a lot about the value of melatonin! Many other substances like curcumin can activate PP-y, but melatonin is produced in significant quantity in the gut. It's almost like somebody planned it that way.

So to me, this is starting to look really interesting.

Short-Chain Fatty Acid Butyrate Repairs the Gut

I continued reading and found out that the SCFA called butyrate has shown the ability to help repair the gut mucosal barrier. Melatonin has shown a similar ability. Plus melatonin in the gut still has the same very important and potent antioxidative stress and anti-inflammatory qualities that it expresses throughout the body.

Still, it has it in even greater numbers in the gut when melatonin production is up to par! Remember, melatonin is produced in the gut at a rate that is at least 400 times that of the pineal gland.

Melatonin also helps to maintain and repair the epithelial cells beyond the mucosal barrier.

Between butyrate and melatonin, this can stop leaky gut or gut permeability which is an inflammatory process when microbes leak from the gut into other areas of the body where they should not be and are attacked through inflammatory processes that create significant collateral damage and more inflammation and oxidative stress. Melatonin and SCFAs work to prevent all of this ill-health promotion in a continuous repetitive health cycle in direct contrast to the oxidative stress/inflammation cycle.

How to Increase Bacteria That Forms Short-Chain Fatty Acids Depleted By Disease

So how do we stimulate this theorized pro-health cycle? It is currently unknown where this process begins, but it is known that the bacteria that can create SCFAs are depleted or very low in disease states, so replacing some of these SCFA producing bacteria seems like a good start.

1. Clostridium Butyricum

Unfortunately, there is only one commercial probiotic bacteria strain that I have found that can produce the SCFA butyrate. It is called Clostridium Butyricum. But it only produces butyrate and not the other two dominant SCFAs, acetate and propionate. Still, as expected, it can have positive health effects, as noted in some studies, but not nearly enough to correct the dysbiosis in the gut.

2. Fasting, Pistachios and Melatonin

Other methods that are said to increase these SCFA producing bacteria are: fasting of various types, pistachios, which not only increase these bacteria but provide the fermentable fiber that the bacteria need to produce SCFAs. And lastly, there is melatonin.

3. Exercise

Another thought is that exercise increases SCFA gut content, but not specifically the bacteria that produce SCFAs.

I'm sure there are more forms, but I need to do more reading to find them. I will update this article when I do.

Prebiotics and Foods Containing Fiber Feed Short-Chain Fatty Acids

Once we have added more of these SCFA producing bacteria to the gut, they need to be fed with prebiotics and foods containing fiber such as apples, pears, oranges, strawberries, pineapple, and other tasty fruits, but there are many other types of fermentable and soluble fibers and prebiotics that can help the SCFA producing bacteria to actually produce SCFAs. Xylitol, FOS, GOS, and Inulin are popular prebiotics that can feed the SCFA producing bacteria.

By the way, it is worth noting that FMT increased gut content of melatonin and SCFAs, which seems significant in terms of what FMT is doing to improve gut performance.

It is also worth noting that if your health issues are not major, it is likely that you have enough SCFA producing bacteria, in which case just a prebiotic, fermentable fiber, and soluble fiber-rich food intake as part of your diet is likely to be sufficient to increase SCFAs and your health with it!

If you add in starving the bad gut bacteria as part of your plan, such as cutting way back on processed food and sugar intake, results are likely to be more impressive and potentially faster since the harmful bacteria are essentially being starved back. This makes it easier for the health-promoting bacteria in your gut to get back in control. Keep in mind that the diet changes you make may not be needed as much or as often once you have a better gut microbiome balance that is more biased toward health-promoting bacteria. Think of how, in the FMT studies, the one-time transplant of FMT lasted at least 12 weeks in all of the participants, and in the 2020 study, 2 participants had their FMT last over two years, which is as long as they did follow up on participants of that study.

It seems odd to me that the SCFA producing bacteria are known enough now, where some enterprising company could have made a probiotic that contains enough of them already, but such is not the case. Such a probiotic with a significant amount of prebiotic to form a synbiotic would be quite useful to help repair gut dysbiosis and broken health.

Many people have related that supplementing melatonin makes them sleepy the next day.

An interesting fact: melatonin produced in the gut does not cause tiredness at any time! If we can get enough SCFA producing bacteria in the gut and feed them with the right fiber and prebiotics, we can test this theory hopefully all the way to good health!

My Personal Experimentation Results So Far

This is a very simplified description of a highly complex process that science has not yet fully elucidated. I did not include descriptions of many other vital pathways and activities that all play important roles in this entire process in order to simplify the overall processes involved in the gut microbiota. The intent here is to see if we can replicate the beneficial effects of FMT via increasing SCFA producing bacteria and subsequently SCFAs themselves, as well as bring the decreased gut melatonin back up to par to maintain the pro-health cycle.

High-Dose Melatonin and Pistachios

I am currently trying to do that through high-dose melatonin and pistachios, and lastly, I intend to incorporate intermittent fasting as a third option. I already do exercise in the form of a two-mile fast walk each day, and this morning I noticed that I set a new record for myself in terms of elapsed time, and I felt good out there this morning.

High Dose Vitamin B-1 (Thiamine)

I am also supplementing high-dose thiamine/vitamin B-1 because it is naturally produced in a healthy gut microbiome, but this production can be disrupted in the presence of gut dysbiosis.

B-1 is very important for many bodily processes and functions. A recent study suggests that it may have potent anti-inflammatory effects, so I want to ensure it is included at least until the gut biome is brought back to a healthier bacterial balance between disease-promoting pathogenic bacteria and health-promoting bacteria.

Since I have psoriasis, it is easy for me to see when something is working or not working because psoriasis can act as a relatively fast responding visual indicator if something is working or not. I have not incorporated intermittent fasting yet, but the little psoriasis I have left is responding positively as noticeable visible improvement each, to every other day, and I may not have enough psoriasis left to test intermittent fasting, but I can live with that!

I should also mention that I have a fairly stressful personal issue in play in my life right now, which would typically have a negative impact on my health and psoriasis, but this time, such is not the case!

The health implications for us are huge and would include many significant diseases such as PD, AD, MS, CVD, Cancer, Psoriasis, Diabetes, Pancreatitis, kidney disease, many types of gut issues, Covid-19, and pretty much any disease that is generally accompanied by gut dysbiosis!

I will update this article if I find new and relevant information to improve on this health-promoting idea or to fill in some blanks.

Art

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