What is a Microbiome?
Many people still refer to bacterial microorganisms as “germs”. Most are completely convinced that “germs” are the inevitable cause of infections and have to be killed with an antibiotic. Few understand that our intestines contain literally millions of bacteria that are essential to our health. The collective nature of these bacteria is referred to as the microbiome. We still do not know how most of these bacteria play their individual part or indeed exactly how they get there. Many studies have been performed and are still being performed in order to research a theme which is relatively new in our everlasting search for the meaning of health. Bacteria are one-celled organisms and have the complexity of our own cells. I will try to provide some kind of bird’s-eye-view of the problem in trying to solve the true and underlying meaning of this microbiome. The variety of different types of bacteria is stupendous and unraveling their individual contributions virtually impossible at the present time.
The Microbiome and Disease
The reader will undoubtedly be surprised and probably skeptical when I refer to the fact that schizophrenia and bipolar disorder, both mental diseases, have been associated with changes in the microbiome. However, it must be understood that although these are serious mental illnesses, they are associated with considerable physiological dysfunction in the body. This dysfunction includes chronic inflammation and what is known as elevated oxidative stress. This can mean that there is either too little oxygen available or too much and that its consumption is either deficient or excessive. Without discussing the details, it must be clear that there is a biochemical disturbance that is associated with changes from normal in the gut bacterial population and the net effect is in the brain. What I found interesting when I read this manuscript was that the researchers had found reduced microbial diversity and global community differences in the microbiome, compared to non-psychiatric comparison samples. In other words, it is the full complement of gut bacteria that appears to be related to health.
The Gut-Brain Axis and the Microbiome
Irritable bowel syndrome (IBS) is one of the most common of all medical disorders worldwide. Although it may have a number of causes, there are now reports of disordered enteric bacterial communities in IBS and that this can influence brain morphology and function. Antibiotics directly affect the gut microbiota and may consequently alter the basic biological processes, imposing severe consequences. Again, we get the impression that it is the full complement and diversity of the microbiome that is associated with the preservation of health. Colonic microbiota synthesize a considerable amount of thiamine in the form of thiamine pyrophosphate (the active form of the vitamin) and require a specific transporter for its absorption. This could contribute to host thiamine homeostasis, especially toward cellular nutrition of colonic cells. The loss of this diversity might be the result of nutritional disturbances, the effect of antibiotic use, or that of other drugs. Are we actually doing more harm than good by the flagrant use of drugs?
Diet and the Microbiome
The Western diet, comprised of highly refined carbohydrates and fat, together with reduced complex plant polysaccharides, has been attributed to the prevalence of obesity. It has been suggested that the concomitant rise in consumption of fructose and sugar substitutes condition the microbiota, resulting in the acquisition of a westernized microbiome with altered metabolic capacity. On the other hand, thiamine is an essential cofactor for all organisms, including bacteria. The role of intestinal microbes play in modulating thiamine availability is poorly understood. Selecting one of the intestinal organisms for research showed that thiamine acquisition mechanisms used by the organism were not only critical for its physiology and fitness, but also provided an opportunity to model how other gut microbes may respond to the shifting availability of thiamine in the intestine. The importance of this is that the variation and ability of gut microbes to transport, synthesize, and compete for thiamine is expected to impact the structure and stability of the microbiota. This variation may have both direct and indirect effects on human health. The authors suggest that targeted thiamine delivery could be used therapeutically to upgrade metabolism of microbiotic communities linked to disease.
Thiamine Depleting Enzymes
There are two enzymes that occur in the human bowel, each of them being synthesized by a different microorganism. Although their function is poorly understood, a little explanation is necessary. Thiamine is constructed from two chemical rings. One is called a pyridinium ring and the other is called a thiazole, attached to each other by what is known as a methylene bridge (CH3). These enzymes attack the methylene bridge, separating the two rings and thus destroying the biochemical action of the vitamin. The curious thing, however, is that the enzymes are also able to bring about the attachment of the two rings, existing independently, thus constructing a metabolically active thiamine molecule.
Whether they attack and destroy or synthesize thiamine is dependent on pH, (indicating an alkaline or acid medium). This may be very important in considering the overall requirement of thiamine in the body and it is not surprising that the action of these enzymes is poorly understood. In fact, the overall bacterial production of the B group vitamins (riboflavin, folate and thiamine) by microbiota is important in further understanding of their effect on host energy metabolism.
End-stage Kidney Disease
An anti-metabolite of thiamine is known as oxythiamine. It has been found that plasma concentrations of this substance are significantly increased in patients with end-stage renal disease. This produces functional thiamine deficiency, contributing to the overall debility experienced by patients. A commentary addresses the significance of this and the potential role of gut microbiota in the generation of oxythiamine. This strongly suggests that adequate doses of thiamine should be given to patients undergoing dialysis
Children with Crohn’s Disease
Fecal samples were collected from 23 children with Crohn’s disease and 21 healthy children. Samples were collected from the sick children before they started receiving parenteral nutrition, during its administration and when they returned to their habitual diets. Disease improvement following parenteral nutrition was associated with an extensive modulation of the gut microbiome. The authors suggested that exploring associations between the gut microbiota and colonic inflammation during parenteral nutrition may offer clues into the microbial origins of Crohn’s disease. The trouble with this is the traditional “chicken and egg” argument. It may mean that the adverse changes in microbiota were an effect from inflammation of the bowel rather than the cause but it is an interesting association.
Children with Autism
Twenty-seven children with autism were compared with healthy controls. Thiamine pyrophosphate (TPP, the active form) was decreased by 24% in autistic children compared with controls. It was particularly interesting that they had normal plasma and urinary thiamine levels (inactive form), whereas the plasma thiamine pyrophosphate concentrations were decreased and there was evidence of oxidative stress. The authors suggested that failure of colonic absorption of TTP from gut microbiota might be the underlying cause of its decreased blood concentration, since the inactive form of the vitamin was normal. The evidence of oxidative stress in autism may reflect changes in mucosal immunity and host-microbe homeostasis and certainly would deserve further research.
There are many different commercially available preparations of probiotics advertised online. The arguments presented are confusing. Some preparations offer the “best bacteria” while others indicate that a wide complement of organisms is required. The research so far suggests that the complete microbiome provides the diversity that meets health requirements and its loss of bacterial components that leads to loss of its efficiency. Since the total complement of organisms in a healthy microbiomes is still unknown, supplementation with a probiotic may or may not have any effect.
It is indeed difficult for us to grasp the fact that our bodies are constructed from between 70 and 100 trillion single-celled organisms, all of which have to cooperate with each other. There is an increasing understanding that our health depends also on single-celled organisms that live in our intestines. We depend on them and they depend on us, a symbiotic relationship. Since they require thiamine as well as their host, it underlines the essential nature of appropriate nutrition. As our knowledge increases concerning our place in world life, we must be collectively insane not to recognize the responsibilities offered to us by evolution. We keep trying to destroy ourselves as well as the world in which we live. The nature of nutrition may emerge as the most important item in the preservation of human health.
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This article was published originally on March 5, 2018.
Hi Dr Lonsdale,
I was wondering if you have any experience with sulbutiamine long term administration? If seems to depress dopamine levels and thus testosterone https://pubmed.ncbi.nlm.nih.gov/10996447/. I am struggling with cfs/me but my testosterone levels were normal. After starting sulbutiamine 400 mg a day, they plummeted.
Will the body be able to compensate given enough time? I don`t have access to another form of ttfd.
With sincere appreciation,
What pH and where, induces what?
“Whether they attack and destroy or synthesize thiamine is dependent on pH, (indicating an alkaline or acid medium).”
Hi Dr Lonsdale,
Would you consider sharing your perspective on a condition such as bipolar disorder? I would love to hear more of your thoughts on this condition in particular, which from what I understand has been growing at an astonishing rate. I am sure I have seen Dr Peter Gotsche suggest in a presentation I saw on YouTube that the rise of bipolar disorder was at least partly attributable to the rise in the use of anti-depressants in the general population.
I am a carer for someone with tardive dystonia and tardive akathesia – some great resources on these conditions (especially genetic factors) and the appalling state of psychiatry in Australia are available from: http://www.drlucire.com Dr Yolande Lucire must be Australia’s biggest whistleblower in psychiatry, and is a private forensic psychiatrist with very explosive information in this field.
I have personally witnessed the person I care for recover in less than 24 hours from a manic episode with one dose (three capsules each) of emu oil and turmeric supplements, which were being trialled for pain from the psychiatric-drug-induced movement disorder that had already set in. No drugs used or needed. I have seen the same manic symptoms resolve on two other occasions also with nutritional supplementation, and very rapidly.
I have seen first hand the devastating effects of these “mental health” drugs as well as the strange revulsion that psychiatrists have for any form of patient / carer enquiry into their practices – simple questions about diagnosis, treatment, drugs, you name it, they really hate questions!!! Treatment success is measured simply as compliance with authority, and non-compliance is obviously a sign of illness!
If you have any light you can shed on this condition in particular, I think the world would benefit. A whole article would be amazing if you had the time / inclination, as I don’t think I have found one yet on this site. Thank you, Sarah
I hate acronyms like SIBO. There seems to be a disconnect here. If the millions of bacterial that make up the microbiome are collectively involved in our health on a symbiotic basis, why should they cause disease if they get into the small intestine? The latest medical literature that I have read concerning the microbiome states baldly that we do not yet know this important symbiotic relationship. They point out that it is antibiotics that kill our friendly bacteria, indicating that they provide a problem, not a treatment. If SIBO refers to “an overgrowth of bacteria”, this surely is not referring to the microbiome unless Dr. SIBO is suggesting that the symbiotic bacteria switch to becoming pathogenic. Or is he referring to an entirely different group of recognized pathogenic bacteria? I must admit that I am confused
Yes it’s definitely another work of science still in progress…..Have you seen one of those comprehensive stool analysis reports? They’re basically trying to link certain types of bacteria to various disease’s. Higher levels of X bacteria are higher in such & such chronic disease. Scientists don’t really know yet what they all do, if good or bad, but are more of a problem if overgrown in small intestine it seems. They absorb your nutrients (b1 ?) when there, and release toxins that travel throughout your body? Antibiotics and their varying effectiveness(some work, some dont) on the many types of bacteria, both good and bad, has altered how the whole system works. This, along with a poor diet (carbs-sugar), leads to more bad guys in the small intestine these days(imbalance). Which leads to disease, perhaps? If you believe Hippocrates, then yes. Dr SIBO seems to think this autonomic intestinal neuropathy leads to all bacteria types in the wrong place. If you add this antibiotics/carb combo, it makes sense you are killing, then growing more bad guys down there than good. I doubt Dr SIBO has looked at Real modern thiamine deficiency as a cause of this neuropathy. Why we need Dr Thiamine’s knowledge here….why we need a lab to do the transketolase test. So hopefully we can find some answers to all these questions 🙂
I really think that it is the present medical model that is the problem. The brain consumes a huge amount of energy dependent on the complex chemistry of oxidative metabolism. Thiamine is a major catalyst for this. I believe that the common diet in America is too high in calories, even if the micronutrients are in sufficient concentration for a healthy organic diet. Oxidative metabolism is overwhelmed like a choked engine in a car. Malfunction of the brain results in distorted signals represented in symptoms. Depending on the distribution of the deficiency and its degree of severity, this gives rise to a constellation of symptoms that are then classified as disease A . Another constellation = disease B.The other obvious factor is the genetics but many genetic traits are insufficient to cause disease on their own. Some form of “stress”,( infection, injury, divorce etc.) coupled with marginal malnutrition, may be necessary to precipitate disease. Thus, thiamine deficiency becomes the common denominator in causing a series of different diseases.
Amen Doc …Amen….and the avoidence of antibiotics whenever possible. No more 5 minutes consults with quick and dirty gut altering prescriptions…Prevention with Nutrition! Another Hippocrates idea, he was a pretty smart guy. With SIBO thought to be in 40 million Americans guts, including mine, it seems to me IV thiamine is the way to go here? Taking orally is mostly just feeding SIBO, consequently most SIBO diets want you to avoid thiamine fortified foods. Does a Meyers Cocktail have enough thiamine in it, and how often would one have to take one? Again not having the transketolase test available makes this another guessing game. These iv’s aren’t covered by insurance as far as I know, and they are not cheap.
It’s obvious from your writing you are younger than what the calender says. Which makes me wonder what the Lonsdale secret is? Are you supplementing with thiamine? No ice cream …ever ? Yoga and yogurt ? “Don’t worry be happy” ? Please share your secret with those of us here searching for answers.
Thanks for writing this piece…you jumped right on it, after we brought it up…very cool Dr T 🙂
Any thought of sending a copy of your book to Dr Pimentel (Dr Sibo) at Cedars-Sinai?