The large intestine has long been thought to be a digestive tract that only absorbs water and some minerals and produces feces. However, more bacteria than the number of human somatic cells reside in the large intestine in a symbiotic relationship with the host. As many as 500 to 1,000 species of bacteria exist in the large intestine, and a symbiotic relationship is formed among them, creating a kind of ecosystem.
These bacteria take in nutrients and metabolize them to produce gaseous components such as hydrogen (H2) and methane and short-chain fatty acids such as acetate, propionate and n-butyrate, producing energy in the process. In addition, some bacteria produce vitamins. The metabolic function of the microbiota in the large intestine is thought to be comparable to that of the human liver, and the gut microbiota can be considered an "organ". Therefore, a drastic change in the gut microbiota due to environmental factors such as high-fat diets and antibiotics could cause changes in the host equivalent to organ damage. It has been shown that disturbance of the gut microbiota (dysbiosis) may be involved in the development of host diseases.
The aim of this laboratory is to elucidate the effects of non-digestible components, especially non-digestible saccharides such as dietary fiber and resistant starch, ingested on the gut microbiota and the physiological effects induced in the host by changes in colonic fermentation using rat and human stools, and to find a relationship with the prevention of lifestyle-related diseases. An overview is given below.
1. Studies on the significance of vitamins in colonic fermentation and vitamins produced by gut bacteria.
This research project has been started for several years and is currently the main theme of our laboratory.
In particular, we have been studying vitamin B12 (VB12; cobalamin), and have recently started research on biotin (vitamin B7).
We started working on VB12 in our laboratory because we presume that VB12 is one of the factors that keep the gut microbiota stable. VB12 is a very complex organic compound with cobalt as a component. Bacteria and archaea are the only organisms on earth that can synthesize VB12, while vertebrates cannot (humans, of course). Although the majority of gut bacteria require VB12, few species of bacteria can synthesize VB12. Therefore, if VB12 cannot be appropriately delivered to the colon, it will be difficult for gut bacteria that require it to reside in the large intestine, and the composition of the gut microbiota will not be maintained normally.
The amount of VB12 consumed in the diet is extremely low, and if the amount of VB12 delivered to the large intestine is insufficient, the composition of the gut microbiota will be disrupted, which could cause disease in the human host. Therefore, in our laboratory, we are studying the following
1） Elucidation of the appropriate amount of VB12 intake, taking into account the maintenance of healthy bacterial flora and fermentation in the colon.
2） Exploring the potential of nutritional supplementation to promote VB12 synthesis by bacteria in the large intestine
3） Identification of gut bacteria with VB12 synthesizing ability
4） Comparison of human and rat intestinal bacteria in terms of VB12 synthesis capacity and colonic fermentation patterns
2. Study on enhanced colonic H2 production due to non-digestible saccharides and suppressive effect of colonic H2 on oxidative stress
H2 molecule has reducing power and alleviates oxidative stress in the body. H2 is produced solely by colonic bacteria, which ferment non-digestible saccharides that escape digestion by host enzymes such as dietary fiber, oligosaccharides, resistant starch, etc. We are exploring the possibility that H2 produced by colonic fermentation could also exhibit reducing power in the body and contribute to health. The aim of this study is to investigate the characteristics of non-digestible saccharides that promote H2 production in the large intestine, and to clarify that the promotion of colonic H2 production contributes to the prevention of diseases by inducing the alleviation of oxidative stress and suppression of oxidative damage in the body.
We found that H2 delivery by colonic H2 in the body alleviates oxidative stress and then suppresses oxidative damage (Br J Nutr 2012).
We also found that colonic H2 generated from non-digestible saccharides diffuses to the abdominal cavity before transferring to abdominal tissues, especially the adipose tissue (Fig.2; J Nutr 2013).
This shows that colonic H2 would contribute systemically to maintain redox balance.
Recently, we found that the alleviation of oxidative stress in the adipose tissue by H2 derived from colonic fermentation is due to electron donation from H2 to α-tocopherol radicals, which promotes their regeneration to α-tocopherol (Fig. 3; Br J Nutr 2020).