Thiamine and the Microbiome

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.

Probiotics

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.

Conclusions

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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Image credit: DataBase Center for Life Science (DBCLS), CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons.

This article was published originally on March 5, 2018.