Gut flora, why is it shocking? What are the great opportunities?

2016-05-06 | Mr. Zealous |

Friendly reminder: You may know a lot of the content of this article, you may not care about some of the content, but there are a few pictures that are worth reading, and the enthusiastic gentleman also translated it into Chinese, which is worth collecting!

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In April of last year, I wrote a less mature science popular science-"Autism, the intestinal flora?", Which wrote :

The study of the intestinal flora is on fire, it is a mess!

Researches related to the past five years not only often dominate the headlines of Nature, Science, and Cell, but also make these top magazines issue additional publications.

Of course, it is also so hot that my doctoral doctor who has left my studies for ten years returned to my specialty.

After one year, the first two sentences have become even worse, just like the latest issue of "Science", with another breath published N blockbuster articles, and "Nature" and "Cell" are often sung by you.I stepped on the stage and desperately cheered up the research on intestinal flora.

Gut flora, tumor immunotherapy, CRISPR, etc. have become the hottest spots in life science.

The third sentence has not changed much. My Tsinghua PhD student is still struggling in the field of entrepreneurship. The difference may be: I have read thousands of documents, gained a little more knowledge, and met some people in the same circle.

It's also a little bit depressed, because the knowledge has increased, and science writing has become cautious, and I dare not write easily.

Fortunately, because of the needs of the project recently I tell you secretly, I wrote a business plan carefully, so that I can have a chance to sort out my knowledge of the intestinal flora.

The content used in the business plan is still a bit dry, and some of them look good by myself. Because I am a little narcissistic, plus "enthusiastic addiction" I accidentally committed it. Today, I just put someThe contents of trade secrets in fact, I have no big secrets are shared.

So, there is light.

Oh no, so I have today's sharing.

We started with some things you need to know about gut flora in the past 8 years :

HMP and MetaHIT

HMP, Human Microbiome Project, human microbiome project it feels very ambitious, isn't it?, Initiated by the American NIH, from 2008 to 2013, it spent 120 million US dollars sequencing company Shuangweiwei, rightSequences of 300 volunteers in various parts of the body were sequenced. It is said that the entire genome of 3,000 microorganisms was cracked, and a human symbiotic microorganism reference database was initially established.

MetaHIT, Metagenomics of the Human Intestinal Tract, Human Intestinal Metagenome Project, initiated by the European Union, 14 research institutions in 8 countries participated, from January 1, 2008 to June 30, 2012, it cost 22 million Euros,3.3 million genes of intestinal microorganisms have been identified and the concept of 3 intestinal types has been proposed.

These two projects were the basic work for the intestinal flora research in full swing later.

Although some scientists have discovered a link between intestinal flora and metabolic diseases before, these two research programs have completely exploded the industry.

To MetaHIT, let me gossip.

When Europeans started this project, they found the cooperation of BGI. At first, their idea was simple: help me sequence well, I paid, but the Chinese's ingenuity finally convinced them. Wang Jun, Qin Junjie, etc.Some people think that the sequencing data has much to dig, and soon became deeply involved in MetaHIT.

In addition to the 3.3 million genes published in 2010, in 2012 and 2013, MetaHIT with the support of Huada published articles on diabetes, obesity and intestinal flora in the journal Nature; in 2014, HuadaThe main team also published an article in Nature Biotechnology to supplement the metagenomic reference genes to nearly 9.88 million!

This campaign, Huada became famous in one fell swoop!

Unfortunately, they have left a lot of people and trained N Huahua companies. Their own metagenomics sequencing business did not go all out, continued to lead the era, and lost the opportunity to rebuild N Huada.

Send Huada a few words: hey!

HMP + MetaHIT + A large number of related research findings :

The number and types of human symbiotic microorganisms are amazing

Human digestive tract, oral cavity, nasopharynx, skin, reproductive tract are full of microorganisms, they are many types, for example: intestinal tract, there are 500-1000 species; in oral cavity, there are more than 600 species; in breast milk, there are also hundreds of microorganisms.!

According to the latest research data, the human body has about 3X10 ^ 13 cells, and the number of symbiotic microorganisms reaches 4X10 ^ 13.

Humans have about 25,000 genes, and each microorganism generally has thousands of genes. Hundreds of thousands of microorganisms add up, there are millions of genes, and the total number of human genes is hundreds of times!

The number of microorganisms and genes are extremely large. They strongly influence or even dominate the fate of people. Uncovering the secrets of symbiotic microorganisms, rewriting human understanding of health and disease, is bringing about a huge revolution in the field of health and medical treatment.

their functions are beyond imagination

Huge amount of human symbiotic microorganisms, with various characteristics, only a few of them are harmful to humans, and most of them are docile, some of them are of great benefit to humans, such as: helping to digest plant fibers that humans cannot use on their ownSynthesize vitamins, absorb minerals, inhibit pathogenic microorganisms, etc.

The picture above shows people's full understanding of microorganisms' participation in human physiological functions.

particularly the role of intestinal microbes

People are gradually clear that the cooperation of intestinal and intestinal microorganisms may be one of the sources of human immunity, and the intestine may be one of the engines of immunity.

Lifestyle, hygiene habits, diet, medicine, etc. will affect the type, number and function of intestinal microorganisms. This makes people's immune system respond differently, or hypersensitivity allergic reactions, or immune deficiency.

Changes in microorganisms and immune system, promote the occurrence of insulin resistance and chronic inflammation, and problems such as metabolic syndrome, obesity, diabetes and even cancer may arise.

Most chronic diseases are related to intestinal microorganisms


After the microbiome project unveiled the mysterious veil of human symbiotic microorganisms, people have studied different chronic diseases and found that basically all chronic disease processes are closely related to intestinal microorganisms.

More than 70% of the human body's mucosal immunity occurs in the intestine. Through complex immune mechanisms, the intestine and intestinal flora are closely related to various organs and parts of the body.

The causes of chronic diseases are very complicated. We cannot rashly conclude that the single factor of the intestinal flora has caused chronic diseases. But as a core element, the role of intestinal microorganisms in the prevention, management and treatment of chronic diseases has been fullyunderstanding.

By using microorganisms as biomarkers to evaluate the progress of chronic diseases, and targeted intervention of microorganisms to control chronic diseases are hot topics in basic and translational research.

More and more factors affecting intestinal health

discovered and researched


Scientists have also determined that intestinal function and health are very susceptible to a variety of factors directly through animal experiments, epidemiological analysis, and clinical controlled experiments.

Some of these factors are congenital, such as the human's own genome; but more of them are acquired, especially dietary habits, exercise, drug antibiotic use, surgery, etc.

By understanding the factors that affect intestinal function and health, and knowing the extent of these factors' impact on microorganisms and human health, a good foundation is laid for precise and targeted intervention of intestinal microorganisms.

Human being has preliminary grasp

The survival law of intestinal microorganisms

With the untiring efforts of the past eight years, especially the past eight years, humans have gradually begun to control the survival laws of intestinal microorganisms, gradually establish a large number of databases, analyze the laws of the population, and help each individual to judge their intestinal microorganismsHave a good foundation for health.

As shown in the picture above, from the human uterus to the infant, adolescent, adult, and old age, what are the distribution of intestinal microorganisms, how feeding, drug use, nutrition and diet will affect them?We all have a preliminary understanding.

Specially speaking, what kind of flora structure is healthy, what does a healthy person's flora look like? In the latest "Science" special issue, there are two heavyweight papers dedicated to it, which is worth checking out.

We even need to re-examine cancer

As mentioned above, the intestinal tract may be one of the engines of systemic immunity. Many studies have also found that they are extremely important in the process of tumorigenesis and may also be a biomarker to predict the occurrence of certain tumors.

Intestinal microorganisms may participate in cancer development in two ways: one is to directly promote tumorigenesis through metabolites or its own components; the other is to indirectly complete the stimulation of tumors by acting on the immune system, etc.

In October 2015, two heavy-weight research papers were published in the journal Science, which also helped the fiery tumor immunotherapy :

One is the discovery that Bifidobacterium promotes cellular immunity with anti-cancer effects and the efficiency of anti-PD-L1 immunotherapy; the other is that the anti-cancer effect of CTLA-4 immunosuppressants depends on the intestinal flora: if it is obtainedThere is no bacteria in the intestine of mice with certain cancers such as killing them with antibiotics, and the anti-cancer drugs against CTLA-4 are not effective; on the contrary, if certain Bacteroides are present, the anti-cancer drugs are effective!

So, many people say that the intestinal flora is upset. Indeed, the importance of fully understanding them has never been understood, that is, in the past few decades, especially the last eight years.

This is the shocking intestinal flora, and what business opportunities are there for them?

Please continue reading :

Research on intestinal microorganisms

Not endorsement of panacea


Well, after talking about the amazing facts about intestinal flora found by humans in the past 8 years, let's take a look at what these studies are useful and what commercial prospects there are.

Let ’s start with the hot and hustle and bustle of probiotics and prebiotics, and just say the day before yesterday :

I recently shared an article in the latest "Science" special issue in the MC system mc.gutgutgut.cn, including a heavyweight review on "Juvenile window flora, education and shaping the immune system."

This is a very neutral scientific literature, but soon several friends in the industry cited this document as an endorsement of the product: Please eat XXX products to make your child ’s intestinal flora good, and to your child ’s body and immune systemit is good.

I have always been cautious about the products recommended to children, so I am also very polite about this :

The intestinal flora in the juvenile window is very important. They will participate in educating and shaping the child's immune system. But how does a child's healthy intestinal flora form? It is not by eating probiotics and prebiotics parents mustYou can't pin your child's gut health on some magic food or medicine, but rely on a scientific and diverse nutritional structure and physical exercise from the beginning of pregnancy to the pregnancy and post-natal stages.

So, some friends who are doing probiotics and prebiotics, the research progress I share is really not used to prove what your products are useful for children or pregnant women. It has been fully confirmed by research that effective probiotics, prebioticsIt may be a part of a maternal or child's food in certain circumstances, but it must not be the protagonist of a scientifically structured diet.

The study of intestinal microorganisms is not an endorsement of a panacea; the latest research results are by no means an endorsement of a specific product.

There is no panacea for all diseases in the world. When we reveal the secret of intestinal microbes, we are not finding a perfect entrance for finding a panacea. We can work hard to find probiotics, prebiotics or drugs related to intestinal microbes.But greater business and market opportunities exist objectively, and we need greater vision and determination.

Related research is actually global and national

The cornerstone of public nutrition and health policy


Mr. Zealous has participated in many entrepreneurial projects, but this choice has made me very excited, because I have strongly felt that when we uncover the secrets of human symbiotic microorganisms, especially intestinal microorganisms, this is important for individuals and businesses.In addition to focusing on seizing a single business opportunity, you can even participate in the revolution of global and national public nutrition and health policies.

Humans have never been able to quantify their own nutrition and health status as they are now. We can quantify and understand the status of public nutrition and food safety through analysis of indicators such as microorganisms. We can formulate corresponding policies to promote government and food companies to haveTargeted promotion of public nutrition and health.

In addition, we can use biological indicators such as microorganisms to find the root cause of chronic diseases and better prevent and control their spread.

Foresighted commercial companies should fully participate in this exciting change, grasp the opportunities for change, and exercise their due social responsibility.

More groups and individuals

The foundation of individualized nutrition and health

For everyone, the study of symbiotic microorganisms also means that revolutionary changes in nutrition, diet, and health management models are coming.

It used to be difficult to quantify the health status of groups and individuals. Now it may be achieved through the detection of several major indicators such as microorganisms; and based on this, we can make targeted changes.

It is extremely difficult to change the human genome. It is practical and feasible to change the expression of microbial genes. We are about to usher in a new revolution in the evaluation and intervention of group and individual nutrition and health.

So, if a person or a company just endorses the study of the intestinal flora as a product that may not be reliable, it may just get a tree and lose a forest.

Enterprises doing prebiotics and probiotics should understand such opportunities and challenges. The research of intestinal flora in the past eight years may not be the carnival of the industry, but the rational beginning of the industry.

We have a simple, convenient and cheap method for quantitative analysis of intestinal flora. Many prebiotics and probiotic functions may be overturned. This must coexist with opportunities and challenges.

In short, the intestine will be a super track in the medical and health field!

What specific business prospects will there be in the end? What are the startups in the United States? What are the seven tracks in China worthy of attention? What kind of things will Mr. Zealot focus on doing? Please listen to the next time!

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Mr. Zealous
Founder of Enthusiastic Bowel Research Institute, Tsinghua Life Science and Medical Alumni Association, Secretary-General of Health blogger, headline article author

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