Difficult to lose weight? Do n’t worry, the method of precise bacteria control has been born!

2015-12-16 | Mr. Zealous |

About the intestinal flora, Mr. Zealous has introduced a lot, in the article "79 super strong microbial knowledge, fully help you to conceive a 99-point superb baby", there are 14 knowledge of 19-32 worthy of everyone's understanding.

The intestinal flora shares our fate with our breathing. They are not just living in our bodies, but more importantly, they are also contributing to our health. For example, various types of human bodies cannot directly digest them.The absorbed plant cellulose and polysaccharides can be converted into short-chain fatty acids and vitamins that are good for the human body with the help of the intestinal flora.

And this is just one example of the multiplicity of intestinal bacteria.

Research over the years has shown that intestinal flora in our growth such as malnutrition, development such as the mature immune system, metabolic diseases such as obesity, infectious diseases such as resistance to bacterial infection and other aspects alsoBoth play an important role.

Many people will naturally think that we can consider adjusting the structure of the intestinal flora to improve people's health. In fact, many scientists are already in action and have made exciting progress.

Today, Dr. Wu Meng and Mr. Zealous will tell you three stories about intestinal flora and obesity. After reading this, you will feel that it is very reliable to lose weight by regulating bacteria.

different flora, fat and thin

In 2013, a scientist from the Gordon Laboratory at Washington University in St. Louis, USA, where Dr. Wu Meng is located, published research results that shocked the world in the journal Science:

For detailed introduction, please see Mr. Zexin's previous article: "Fat and thin" destined "? Weight loss, can you find a thin person to live with?"

Simply put: it is to transfer the intestinal flora of the twin sisters who are different from each other extracted from the stool to the intestines of the mice feed them to eat, and then separate them and feed them.Healthy food, mice that transferred the fat sister flora fat bacteria mice became fat, while mice that transferred the lean sister flora lean bacteria mice were relatively thinner.

This fully demonstrates that the intestinal flora can affect fat and lean, and what the scientists found later is even more magical: they put fat mice and lean mice together and keep them healthy as well.Food, fat mice are no longer fat!

Originally, similar to dogs, rats are also animals that eat poop! In a cage, fat mice will eat poop of lean mice, and the intestinal flora will complete the nature during the meal.Exchange options.

"Born" fat mice with fat bacteria, so they were "infected" with lean bacteria by lean mice, but they did not gain weight! Fat mice did not "infect" lean mice!

Uh ⊙o⊙ ... this is such a good thing!

Unfortunately, dogs and rats ca n’t change their poop, and they wo n’t change it. This is their way of survival, but people ca n’t, they ca n’t eat it ... so fat people want to please thin people, and hope that thin people can infect some thin bacteriareality.

Moreover, if you give fat mice unhealthy high-fat and high-sugar foods, they will live with more lean mice and eat more ... omitting the word here will not have goodLean bacteria, naturally will not lose weight.

So, to lose weight, it is always critical to keep your mouth shut.

But do n’t be discouraged, we still have many ways to change the structure of the intestinal flora, so as to achieve partial weight loss.

AKK bacteria, reliable weight loss probiotics?

There is a reliable method to study which bacteria are good for intestinal health, can help lose weight, and then consider developing them into probiotics.

In the article “Lard Destroyed Gut: What Oil to Eat, What Bacteria to Injury, and What Fat Gain?”, Mr. Zealous introduced a new research in 2015: keep other food ingredients the same, and only make the fat types different., If the fat in the recipe is lard, the mouse will be fatter, and the gut bacteria and bacteroides are more in the intestine :

If the fat in the recipe is fish oil, the rat is awesome, and there are many AKK, Lactobacillus and Bifidobacterium in the intestine :

Note this AKK bacteria, its full English name is: Akkermansia Muciniphila, there is currently no Chinese translation, so we call it AKK bacteria.

Does anyone think of AK47? Do you want a sharp weapon like AK47 to help you lose weight?

Scientists say that AKK bacteria are really reliable for weight loss!

AKK bacteria can thicken the intestinal mucus layer, improve metabolism, help consume more energy, and do not make people gain weight.

Special to tell you that some AKK bacteria in the intestines of some fat people are 100 times less than normal people.

So, AKK bacteria has become a popular weight loss probiotic, and I don't know if any company is making related products. Chinese pharmaceutical companies and probiotic factories can try it.

More reliable: development of prebiotics targeting AKK bacteria

Prebiotics, simply the food of probiotics. It can specifically stimulate the growth of one or more bacteria that are good for health. Common prebiotics are :

People have been relatively clear that many of the above prebiotics can stimulate the growth of bifidobacteria in a targeted manner.

Of course, Mr. Zealous also secretly told you that they can basically stimulate the growth of AKK bacteria, which is the food that AKK bacteria will eat, but the effect of stimulating AKK bacteria is not as obvious as that of Bifidobacterium.

Can you find crackling three, five, and two in addition to prebiotics that can stimulate AKK bacteria?

The answer is yes!

Before October 2015, the workload will be huge and the development time will be very long. You must constantly try candidate prebiotics; however, Dr. Wu Meng and colleagues announced a powerful prebiotic development in ScienceAfter the tool, things are relatively simple.

Let ’s look at the summary diagram of this heavy research by Cell Metabolism :

Is it a bit crazy to see it? The enthusiastic Mr. Gently turned around after seeing it too! So I specially invited Dr. Wu Meng to explain in person :

We started from the intestinal flora itself, combined with microbial genetics and genomics, and developed a new method for intestinal flora research: Multi-taxonInsertion Sequencing INSeq, using high-throughput sequencingTechnology to dynamically detect the effect of diet on the structure of intestinal bacteria and identify genes that regulate bacteria's ability to adapt to changing foods, paving the way for new probiotics and the components that can promote the growth of these probiotics-prebiotics.

Step 1: Use "barcode" to build mutation library

Specifically, the first step of this method is to put a "barcode" on the bacteria. We use microbiological genetic experiments to detect 4 types of common bacteria in the human intestinal tract, Bacillus cellulolyticus, O. ovale, and twoB. polymorpha subspecies with genetic mutations.

We inserted transposons with barcodes into their genomes, resulting in loss of gene function at the insertion site, resulting in a mutant strain with a specific gene deletion. By adjusting experimental conditions, for each species,We have created corresponding mutation libraries that contain millions of heterologous transposon mutants, covering all non-essential genes.

Under certain circumstances, the growth rate of some mutant strains will slow down, resulting in their relative abundance in the entire intestinal flora. As a result of the existence of barcodes, through genome sequencing, we can accuratelyDetect insertion sites for these mutants, identify mutant genes, and obtain the relative abundance of each mutant.

By comparing the changes in the abundance of each mutant strain in this environment, we created a statistical model and calculated the "health index" of each mutant strain in that environment. Mutant strains with a significantly lower "health index"The mutant gene is an important gene for bacteria to adapt to the environment.

Step 2: Establish a mouse model that simulates the human intestinal environment

With the mutation library, the second step is to establish a mouse model of "human intestinal flora." We transplanted human intestinal bacteria 11 wild strains? Four mutation banks to a sterile isolation systemBreeding and breeding mice in vivo, so that they only carry human intestinal bacteria, become "humanized" mice from the perspective of intestinal flora.

Then they are fed different human foods: typical western foods represented by high fat and high sugar, and healthy foods with low fat and high plant cellulose.

The third step: dynamic monitoring of intestinal flora changes

Next, the second-generation sequencing method was used to dynamically monitor the changes in flora structure and gene expression in mice fed different foods.

The sequencing data of these mutant libraries gave us the first opportunity to study at the genetic level how the intestinal flora adapts to different environments.

By comparing the sequencing data, we can accurately record the abundance changes of each mutant before and after being placed in the mouse. Those mutants whose gene function is lost due to transposon insertion and whose abundance has significantly decreased will be recorded.These are the mutants we are looking for because their mutant genes are genes that play important roles in this environment.

Step 4: Verify the corresponding prebiotic is valid after finding the gene

The last is the most exciting step. Can we find new ways to regulate the structure of the intestinal flora?

In the 2013 experiment described above, we found that one of the important bacteria transmitted by "lean mice" to "fat mice" is cellulolytic bacteria.

In a new study, we found that Bacillus deficiens grows happily in low-fat, high-fiber healthy foods, accounting for almost half of the total flora, but it suddenly decreases in high-fat, high-sugar foodMore than half.

Can we find a way to make them grow happily in western food?

By Multi-taxon INSeq, we found that the mutant strains of Fibrobacterium bacillus have a gene cluster that only show a lower health index than other foods in Western foods.Growth in food plays an important role.

Can we use it as a target?

Through in vitro experiments, we found that the most common cereal hemicellulose arabinoxylan is the substrate of this gene cluster, so we decided to add hemicellulose arabinoxylan to the drinking water of mice, we foundThe relative abundance of cellulolytic bacteria suddenly increased to a higher level than in healthy foods, and it was food-specific and species-specific, which fully verified our hypothesis.

How about? Maybe you still don't understand it! It doesn't matter, check it more.

Mr. Zealous also took more than a month to finally understand the details of this technology and was very excited about its application prospects.

Why? See Dr. Wu Meng and me for a discussion of the possible prebiotics this technology may use to develop AKK bacteria :

Understand? When you find a probiotic that can lose weight, in addition to making it directly, it is more reliable to try to find a prebiotic that can make it grow better in the intestine!

Screen genes, determine substrates, actual verification may be completed within weeks.

If successful, AKK bacteria need not share prebiotics such as oligofructose with bifidobacteria, etc. Therefore, to lose weight, eat prebiotics targeting AKK bacteria, the effect may be full.

Overall, the establishment of this method, like the leader of this research project, Professor Jeffrey Gordon, a double academician of the American Academy of Sciences and Medical College, said that it laid the foundation for future research on intestinal flora function, showing that we canPrebiotics are designed to precisely regulate the intestinal flora.

Precise regulation is the legendary targeted regulation!

References

Everard A et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci US A. 2013 May 28; 110 22: 9066-71.

Dao MC et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2015 Jun 22. pii: gutjnl-2014-308778.

Wu M et al. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides. Science. 2015 Oct 2; 350 6256: aac5992.

Cani PD, Everard A. Harnessing Genes and Diet to Fine-Tune the Gut Microbial Fitness. Cell Metab. 2015 Nov 3; 22 5: 754-6.

Caesar R et al. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metab. 2015 Oct 6; 22 4: 658-68.

Bindels LB et al. Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol. 2015 May; 12 5: 303-10.


This article was written by Mr. Zealous and Dr. Wu Meng from Washington University in St. Louis, USA.

Dr. Meng Wu: 2002-year undergraduate alumni of Tsinghua University, a proud student of Jeffrey Gordon, a pioneering figure in the field of intestinal microbiome research, the first author of the heavy paper in Science Magazine in 2015

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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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