Seven fullness + high fiber can improve the flora and prolong life?
Gut · Tours | Can Full Saturation + High Fiber Improve Bacteria and Prolong Life?
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Good evening everyone, thank you for your kind invitation. My name is Zhang Chenhong, State Key Laboratory of Microbial Metabolism, School of Life Science and Technology, Shanghai Jiaotong University.
I have been doing some research on the relationship between intestinal flora and chronic metabolic diseases, such as obesity and type 2 diabetes, with Zhao Liping since my PhD.
But today, what I want to share with you is flora and aging and life span.
Forever young, immortal, this is probably a dream for all human beings.
For example, in Nordic mythology, the Goddess Eaton has a youth golden apple, which can help the Nordic gods to maintain their youth. There are also myths and legends in China, and Xu Fudongdu went to Qin Shihuang to find elixir of immortality.
During the development of science, we have also made a lot of research on which pathways are involved in our life span, aging, etc., and what they are related to.
For example, in the study of humans, mice, nematodes, etc., what has aging been related to?
It is related to the decline of the stability of the genome, the decrease of telomere length, the change of epigenetics, the change of the stability of proteome, the loss of control of nutrition perception, the loss of mitochondrial function, the aging of cells and the decrease of stem cells,Changes in the signal of the cell-to-cell dialogue and so on.
However, these are some changes of the host itself. We all know that there are a large number of microorganisms symbiotic with us in the intestine. So, what role do these little partners play in our aging and life?
As early as 1907, Nobel Prize winner Mechenikov once put forward a hypothesis. He believes that some toxic and harmful substances produced by the intestinal flora will enter the host's circulatory system and cause us toAging.
But this is only a hypothesis, because the research conditions at the time did not allow it to be verified.
With the development of science and technology, our understanding of flora is getting deeper and deeper.
We have established an intestinal flora after birth and have remained relatively stable after adulthood, which has accompanied us throughout our lives. But in the state of aging, due to various changes in our lifestyle, physiological and immune systems, and intestinal characteristics, Our flora has changed accordingly.
A lot of studies have compared the difference between the flora of the elderly and healthy young people. One of the great characteristics is that in the process of aging, the number of actinomycetes is reduced, and the proteobacteria are reduced.This class of bacteria is increasing. Of course, in the study of different populations, many different conclusions have been reached.
How exactly does our flora change with aging? What is the molecular mechanism of the effects of microorganisms on the aging process and lifespan of the host? These need further research.
Scientists use some simple model organisms to study, such as C. elegans and Drosophila melanogaster.
Why? Because their genetic background is very clear, and their life cycle is very short. If we want to use model organisms such as mice or monkeys to study life span and aging, it may take a very long time.
The life cycle of nematodes and fruit flies, only a few weeks, or even shorter, is a good model animal. Moreover, their symbiotic microorganisms are also relatively simple, so they are commonly used models in aging research.
For example, in the research of nematodes, we feed the nematodes with E. coli OP50 as its nutrient in the laboratory, so this bacteria has become its symbiotic microorganism.
Scientists have found that, unlike mammals, nematodes cannot produce a very important signaling molecule, nitric oxide NO, but rely on OP50. Nitric oxide can regulate nematode life-related gene expression, soIt plays a role in worm life.
On the other hand, a non-coding DNA sequence of E. coli OP50 is very similar to a gene related to lifespan regulation of nematodes, which can regulate this gene to some extent and also affect the lifespan of nematodes.
In addition, the metabolites produced by bacteria can affect the lifespan of nematodes. For example, we know that a "magic drug" metformin, in addition to being a first-line treatment for type 2 diabetes, has been used in many animal studies.Found it to extend life.
And through the study of nematodes, it was found that metformin does not directly affect the pathway of nematodes, but affects the synthesis of folic acid by OP50 of E. coli, reduces the formation of methionine, thereby affecting the AMPK pathway of the nematodes and prolongingLife of nematodes.
Another aspect, microorganisms can affect the nutritional status of its host. For example, in the oligotrophic state, adding Lactobacillus to fruit flies can improve the growth and development of fruit flies.
In addition, different strains and strains have different effects on the life of the host. Nematodes were originally insects that lived in the soil. In the laboratory, we were fed E. coli OP50, but it was in the soil.Eat another bacterium.
Nematodes have a shorter lifespan when eating that kind of bacteria than OP50. Even if 1% of this soil-derived bacteria is added to OP50, the lifespan of nematodes will be shortened.
In a recent study, scientists mutated nearly 4,000 genes in E. coli and obtained nearly 4,000 mutant strains, and found that 29 of them are related to the lifespan of nematodes.
Twelve of these 29 genes are not only related to the length of life, but also to the occurrence of tumors and β-amyloid deposition during aging.
The molecular mechanism of the role of 5 genes is to increase an acid capsular polysaccharide colanic acid produced by Escherichia coli, which affects the mitochondrial function of the nematode and the response of unfolded proteins, etc., and then affectsLife of nematodes.
These are some conclusions obtained from simple model organisms. And we know that the mammal's intestine is very, very complicated, and the flora inside it is very, very large. Then the flora affects mammalian aging andWhat about the life mechanism?
A recent mouse study found that the flora of aging mice will change, which will destroy the host's intestinal barrier function, resulting in an increase in host systemic inflammation.
If a very important gene related to systemic inflammation, TNF-α, is knocked out, the effect of systemic inflammation caused by the flora of elderly mice will not exist.
So in mammals, the intestinal flora also plays a very important role in aging and longevity. But what kind of bacteria have played such a role needs further research. And these bacteria and hostThe specific molecular dialogue between them also needs to be further revealed.
Since the flora is so important in aging and longevity, we can improve our flora through regulation, such as using dietary intervention, prebiotics, probiotics, or faecal transplantation, which is very popular now, to transplant young and healthy flora toAging individuals, etc., can these interventions prolong life and improve aging?
One of the most widely recognized dietary interventions that can prolong life is dieting-dieting that does not cause malnutrition. Reducing the amount of food by about 40% to 20% will not cause malnutrition.
This method has been confirmed in very many creatures such as worms, spiders, monkeys, fish, mice, rabbits, etc., and it can indeed prolong life.
Of course, be careful not to cause malnutrition and not to over diet.
So does dieting play a role in human aging and life? Of course, it is not realistic to do dieting experiments for people throughout the life cycle.
However, scientists conducted a short two-month dieting study and found that it can indeed improve the expression of many pathways related to aging. In other words, it can affect aging and life expectancy.
A life-cycle study of dogs and monkeys found that the metabolites of the host changed by dieting are aromatic compounds containing benzene rings.
These compounds are co-metabolites of the intestinal flora and the host, that is to say, dieting can significantly change the flora, and the flora may be important in dieting.
So, we cooperated with Professor Liu Yong of the Institute of Nutrition to conduct a full-life cycle diet experiment for mice. After weaning the mice, we reduced the food intake by 30% until it died naturally.
We found that the diet group actually delayed aging and increased life expectancy by 20% compared to free-fed satiated mice. The average life expectancy of C57 mice was about 1,000 days.Life can reach about 1300 days.
We also found that dieting significantly changed the intestinal flora of mice.
This mouse has a very special flora structure, and the bacteria that change in it are significantly related to the lifespan of the mouse and some of its metabolic indicators.
So what kind of flora does dieting cause? It is a flora with absolute abundance of Lactobacillus. How much can Lactobacillus account for? It can account for 20% of mouse intestinal bacteria.
Everyone knows that one type of bacteria accounts for more than 20% in the intestine, which is a very high proportion. Mice only need to diet for 14 days to form such a special flora structure, accompanied byDiet mice for life.
On the other hand, such a flora structure will reduce some of the antigenic substances produced by the flora into the host's circulatory system, so the systemic inflammation in mice is also reduced.
Not only that, we injected chemotherapeutic drugs to dieting mice and found that the intestinal mucosal damage and intestinal stem cells caused by chemotherapeutic drugs were reduced and improved. That is to say, after I used a diet to create a more optimized flora, it could reduceIntestinal side effects from chemotherapy drugs.
Since such a bacterial group dominated by Lactobacillus is so important, does the very abundant Lactobacillus really play a role in extending life and improving aging?
We isolated this Lactobacillus from dieting mice and obtained two strains of Lactobacillus. They were found to be Lactobacillus mucus and named CR141 and CR147 respectively.
We sequenced the whole genome of these two strains and found that their genomes are very, very similar, with a similarity of 99.6%. Of course, they still have some functions and genes that are different.
In in vitro tests, we found that only one of the strains, CR147, has a significant anti-inflammatory effect and can reduce the interleukin 8 produced by Caco-2 cells induced by TNF-α. Only CR147 has this effect, andCR141 does not.
We added CR147 and CR141 to E. coli OP50 and fed them to nematodes. We found that only CR147 can significantly extend the lifespan of nematodes, and CR141 has no such effect. So only one of the two strains like this has this effect.
Then, we collected the feces of old mice. The mice at 18 months have entered the senescence period, and their intestinal flora has changed significantly.
We collected the feces of these elderly mice, incorporated this CR147 in a high abundance ratio, and then transplanted it to sterile animals. We found that CR147 can indeed improve the intestinal barrier function damage and the smallSystemic inflammation in mice.
That is, CR147 does have a protective effect on aged mice.
Our studies show that dieting can significantly change the flora of mice, and can create a very specific Lactobacillus-based flora, reducing the entry of flora antigens into the host's circulatory system, thereby enabling the host to improve aging,extend your life.
And this effect is strain-specific, only CR147 among them has the effect of reducing systemic inflammation related to aging.
So, what does this research mean to people? Many people are asking, can I eat this Lactobacillus ratus CR147 as a probiotic to prolong life and delay aging?
I think so, first of all, we must study why CR147 strain can protect the intestinal barrier and anti-inflammatory effect. We find its corresponding metabolite, or some related proteins, and we can develop some smallMolecular substances may be used clinically.
On the other hand, we need to find bacteria with similar functions in the human body, which may be more suitable as human probiotics.
Intervention against flora can help us build an optimized intestinal flora structure to help us extend life and delay aging.
And the intervention against the flora may be much easier than the intervention against the human. Because we can change the culture medium of the bacteria, that is, our diet and nutrition, etc., this way may be saferAnd simple.
How to eat can prevent aging and prolong life?
In the mouse experiment just now, we reduced the mouse's food intake by 30%, which means that it actually ate a full stomach. This is in line with our ancient wisdom of Chinese people: full stomach can extend life.It happens. From animal studies it does.
Then everyone will ask, what exactly is 70% full? For mice, we can strictly control the amount of food we eat, what do people do?
I can tell you what Qicheng's feeling of fullness looks like: that the stomach is not feeling full, but your desire to eat has fallen, and the speed of active eating will also decrease, but you will continue to get used to iteat.
So you have to divert your attention at this time, you will not continue to eat after you divert your attention. This way you can maintain a full stomach. This may be a good way to benefit everyonehealth.
Another way to interfere with the flora is to increase the amount of dietary fiber we consume.
The high dietary fiber diet has a very good effect on the improvement of the flora, in chronic metabolic diseases and some other diseases related to aging. In this regard, many studies have been reported in our research group.Already.
So, as a scientist, as a person who studies the flora, we will continue to interpret the role of the flora in the lifespan and aging of the host, as well as its molecular mechanism, to find the really key functional bacteria.
For everyone here, I hope you can use a reasonable diet, full satiety, high dietary fiber, etc. to maintain a healthy intestinal flora structure to help you live longer.
"Gut · Tao" is a TED lecture column recorded by the Enthusiastic Gut Institute. This article is the first recorded guest of Zhang Chenhong in the fifth session. Picture:/ s / 6576a852c4354279882da02ca70d9b33
Zhang Chenhong, Researcher, State Key Laboratory of Microbial Metabolism, Shanghai Jiaotong University
Enthusiastic Think Tank Expert
Researched in the field of the relationship between intestinal flora and obesity and other metabolic diseases for nearly 10 years, and made outstanding achievements in improving obesity and type 2 diabetes through nutritional regulation of intestinal flora.Excellent Doctoral Dissertation of Shanghai.
Hosted the National Natural Science Foundation of China Youth Project, was selected to the Shanghai Science and Technology Commission Yangfan Talent Program, was selected as the fourth batch of “National Ten Thousand People Program” young talents, and has undertaken important research projects in a number of National Natural Science Foundation projects and “863” projectsjobs.
Published more than 30 papers in SCI papers, including 12 papers published by the first author or corresponding author in the internationally influential journals Science, Nature Communications, and ISME Journal.
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