MiZ Co., Ltd.
“The Overlooked Benefits of Hydrogen-producing Bacteria” was published in the academic journal Medical Gas Research.
A review article “The overlooked benefits of hydrogen-producing bacteria.” with MiZ Co., Ltd., University of California, Berkeley, and Keio University was published in the Dutch academic journal Medical Gas Research. (2023, Volume 13, Issue 3, Pages 108-111). This paper was adopted for the cover of Medical Gas Research.
Article URL: https://www.medgasres.com/preprintarticle.asp?id=344977
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1. introduction
Foods containing lactic acid bacteria, bifidobacteria, etc. are ingested all over the world. In the food industry, for commercial purposes, bacteria such as lactic acid bacteria and bifidobacteria that have beneficial effects on human health are classified as “good bacteria”, and bacteria that cause opportunistic infections such as sepsis are classified as “bad bacteria”. Beneficial bacteria such as lactic acid bacteria and bifidobacteria produce short-chain fatty acids by digesting dietary fiber, induce regulatory T cells, and maintain homeostasis in the intestinal tract.
On the other hand, among intestinal bacteria, hydrogen-producing bacteria called hydrogen-producing bacteria are anaerobic bacteria. , unable to grow in the presence of oxygen. However, these anaerobic bacteria possess the enzyme hydrogenase and can produce hydrogen. Hydrogenase is an enzyme that reversibly catalyzes the production and decomposition of hydrogen molecules through redox reactions. Until now, hydrogen has been thought to be inert in the body and not metabolized in the body, so it has not been noticed by modern medicine, which originated with Hippocrates in ancient Greece. It is a substance that should be Hydrogen-producing bacteria include pathogenic bad bacteria, but their occupancy in the intestine is usually kept low. On the other hand, there are also hydrogen-producing bacteria that benefit human health. Here, we focus on
hydrogen-producing bacteria that act as beneficial bacteria with unimaginable benefits to human health.
2. Super Good Bacteria – Hydrogen Producing Bacteria –
From birth to death, human beings continuously generate hydroxyl radicals, which are highly reactive and highly toxic, from the oxygen taken in by respiration inside mitochondria, which are intracellular organelles. Hydrogen molecules, being the smallest diatomic molecules, easily permeate mitochondrial membranes and protect cells from oxidative stress by reacting with hydroxyl radicals generated inside mitochondria. It is no exaggeration to say that molecular hydrogen is the only antioxidant that can scavenge hydroxyl radicals inside mitochondria without side effects. Therefore, it can be said that hydrogen-producing bacteria are far superior to good bacteria such as lactic acid bacteria and bifidobacteria that cannot produce hydrogen. Despite this, not only the food industry, but also the medical and pharmaceutical societies did not turn their attention to
hydrogen-producing bacteria. In view of this background, we call hydrogen-producing bacteria that bring health benefits “super good bacteria”.
3. Benefits of Hydrogen-Producing Bacteroidetes and Firmicutes It is said that more than 1,000 types of intestinal bacteria of approximately 100 trillion exist in the large intestine of humans. Among them, 70% of intestinal bacteria are hydrogen-producing bacteria that have hydrogenase, which is an enzyme for hydrogen metabolism, and metabolize carbohydrates to produce hydrogen together with acetic acid, butyric acid, etc. (3). According to a metagenomic survey, the hydrogen-producing bacteria in the human large intestine are predominantly Firmicutes and Bacteroidetes, with Firmicutes at 51% and Bacteroidetes at 41%, totaling 92%. As mentioned above, hydrogen has been thought to be an inert substance in the body and not to be metabolized. explain the core of
Bacteroidetes form colonies by binding dimeric IgA antibodies and settle in the mucus near intestinal epithelial cells, from which they constantly produce hydrogen. It can be calculated that about 10 liters of hydrogen is produced from the human intestine per day. The hydrogen produced scavenges hydroxyl radicals in intestinal epithelial cells to protect the intestinal wall from oxidative stress. Excess hydrogen permeates the cell membrane by diffusion, and part of it enters the blood stream and circulates throughout the body (Fig. 1). It can be said that the membrane permeability and diffusibility of hydrogen are one of the excellent characteristics not found in pharmaceuticals. It is known that the concentration of exhaled hydrogen produced by intestinal bacteria depends on the pH and hydrocarbons in the intestine. Therefore, it is thought that the hydrogen in the blood stream reaches the head, and the hydrogen permeates the blood-brain barrier and enters the brain to protect the brain from oxidative stress. Since oxygen (O2), which is a diatomic molecule similar to hydrogen (H2), penetrates the blood-brain barrier and is used in brain cell respiration, it is easy to imagine that hydrogen molecules can also penetrate the blood-brain barrier. . It has been reported that there are fewer Bacteroidetes in dementia patients than in healthy subjects. Although this report does not mention hydrogen, the lack of Bacteroidetes results in less hydrogen being produced in the intestines, so that biological substances such as DNA and proteins in brain cells are attacked by hydroxyl radicals. It can be imagined that this is the cause of dementia.
Colonies of the aforementioned Bacteroidetes and dimeric IgA antibodies promote the metabolic function of Firmicutes, another hydrogen-producing bacterium that dominates the human large intestine, and as a result prevent the promotion of enteritis. Firmicutes is also known as a butyric acid-producing bacterium, and it has been reported that butyric acid bacteria are significant in healthy long-lived elderly people. Butyric acid produced by Firmicutes prevents and suppresses colorectal cancer via the p21 gene, and there are reports that the number of butyric acid bacteria is significantly lower in patients with ulcerative colitis and Crohn’s disease, but this is due to butyric acid. It can be imagined that not only the effect but also the hydrogen produced by butyric acid bacteria has an effect. As a substance that activates Firmicutes, mucus-associated functional factor (MAFF) is assumed as a gene whose function is unknown. However, considering that hydrogen is what protects against the promotion of enteritis here, it is strange to think that the interaction between hydrogen-producing bacteria, Bacteroidetes and Firmicutes, contributes to the maintenance of human health. is not. In fact, there is also a report that delivery of hydrogen to the gastrointestinal tract by ingestion of hydrogen water regulates the activity of
hydrogen-producing bacteria and improves the clinical characteristics of intestinal flora disorders.
Google’s subsidiary Calico (South San Francisco, USA), which is conducting research and development aimed at preventing aging and related diseases, uses naked bar rats as experimental animals. Naked rats live about ten times longer than common rodents and are more resistant to cancer. It has been reported that Bacteroidetes and Firmicutes are dominant when examining the intestinal bacteria of naked bar rats. This suggests that hydrogen produced by Bacteroidetes and Firmicutes may be involved in the longevity and cancer resistance of naked bar rats.
Since hydrogen has the properties described above, it can improve intractable diseases such as Parkinson’s disease and cancer caused by oxidative stress, which cannot be improved by modern medicine and pharmaceuticals. From these facts, it is no exaggeration to say that hydrogen-producing bacteria are “super good bacteria”.
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Figure 1. (1) Bacteroidetes bound to dimeric IgA antibodies colonize intestinal epithelial cells. (2) Bacteroidetes produce hydrogen; (3) The produced hydrogen eliminates hydroxyl radicals generated inside intestinal epithelial cells and protects the intestinal wall from oxidative stress. (4) Hydrogen generated from Bacteroidetes colonies may activate Firmicutes metabolism. (4) The surplus hydrogen diffuses, and part of it enters the blood stream and circulates throughout the body.
4. Hydrogen-Producing Bacteria and Disease – Possibility of Hydrogen Involvement in Gut-Brain Correlations –
Comparing diseases associated with disruption of the composition of the intestinal flora (dysbiosis) and diseases confirmed to be ameliorated by hydrogen reveals that there are many overlapping diseases. Known diseases associated with the above-mentioned Bacteroidetes include intractable diarrhea, Crohn’s disease, irritable colitis, SIRS, inflammation, Parkinson’s disease, rheumatism, cancer, arterial disease, dementia, and premature birth. Known diseases include refractory diarrhea, Crohn’s disease, irritable enteritis, SIRS, ulcerative colitis, and depression. It can be speculated that common mechanisms may underlie diseases associated with dysbiosis and those ameliorated by hydrogen. In other words, it can be considered that the cause of diseases related to dysbiosis is the decrease in the supply of hydrogen to the body due to the decrease in
hydrogen-producing bacteria. For example, patients with Parkinson’s disease, rheumatoid arthritis, cardiovascular disease, Crohn’s disease, and dementia have been found to have a low number of hydrogen-producing bacteria in their intestines and a low hydrogen concentration in their breath. It has also been demonstrated that hydrogen produced by intestinal hydrogen-producing bacteria is effective against concanavalin A-induced hepatitis.
As mentioned above, hydrogen can easily penetrate the blood-brain barrier and enter the brain, so it can also eliminate hydroxyl radicals generated in the brain. Hydrogen that enters the brain protects brain neurons from oxidative stress and improves diseases caused by cranial nerve disorders such as depression and dementia. In the Society of Enterobacteriology, the bidirectional relationship between the brain and the intestine is called “brain-gut correlation” or “gut-brain axis”, but hydrogen produced by hydrogen-producing bacteria is the center of “brain-gut correlation”. must play a role. It has been reported that (1) intestinal bacteria, (2) oxidative stress, (3) inflammation, and (4) mitochondrial dysfunction are closely related to psychiatric disorders such as depression. Hydrogen is not mentioned in this report. However, the mechanism that hydrogen produced by hydrogen-producing bacteria reduces oxidative stress in the whole body, including the brain, suppresses mitochondrial dysfunction and inflammation, thereby improving mental illness. In light of this, it is easy to imagine that hydrogen plays a central role in improving disease.
5. Hydrogen Will Achieve Healthy Longevity
People with few hydrogen-producing bacteria in their intestines can supply hydrogen to their bodies by inhaling hydrogen gas or drinking hydrogen water. Hydrogen-producing bacteria having hydrogenase can not only produce hydrogen, but also can create energy by decomposing hydrogen. Hydrogen-producing bacteria can also save energy by decomposing hydrogen with carbon dioxide into acetic acid and methane, and reducing sulfuric acid with hydrogen into hydrogen sulfide. From this fact, it is possible to increase the number of hydrogen-producing bacteria by supplying hydrogen to the body.
In joint research with a research group at the Osaka University School of Medicine, the authors of this paper clarified that the
administration of hydrogen water to sepsis model mice for 7 days suppressed the bacterial translocation that causes sepsis. It was also confirmed that the number of hydrogen-producing bacteria,
Bacteroidetes, increased. An increase in hydrogen-producing bacteria in the intestine results in the production of more hydrogen in the intestine, which contributes to the maintenance of health.
There is a correlation between the amount of hydrogen produced by hydrogen-producing bacteria and the hydrogen concentration in exhaled breath, and the hydrogen concentration in exhaled breath is used as a useful index of hydrocarbons metabolized by intestinal bacteria. It has been reported that hydrogen concentration in exhaled breath of centenarians in Japan is higher than that of diabetics with an average age of 79 years. It is thought that the hydrogen produced by hydrogen-producing bacteria in the body protects us from oxidative stress and contributes to longevity.
Far from “healthy longevity”, hydrogen may not be a dream to realize “immortality”. This is the reason why hydrogen-producing bacteria can be called “super good bacteria”.
Japanese title: The overlooked benefits of hydrogen-producing bacteria English title: The overlooked benefits of hydrogen-producing bacteria. Authors: Dr. Yusuke Ichikawa (Science) 1,2, Tan Yamamoto 2,3, Shinichi Hirano, Ph.D. (Veterinary Medicine) 1, Bunpei Sato 1,2, Yoshiyasu Mutoh, Ph.D. (Engineering) 3, Fumitake Sato 1,2
Affiliation: 1. Research and Development Department, MiZ Inc., MiZ Inc. CA, USA, 3. University of California, Berkeley, 4. Faculty of Data Science, Musashino University, 5. Faculty of Environment and Information Studies, Keio University
Article URL: https://www.medgasres.com/preprintarticle.asp?id=344977
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This paper was adopted for the cover of Medical Gas Research Volume 13.
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