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This article is original by Translational Medicine.
Please indicate the source for reprinting.
Author: Daisy Guide: Recently, a study published in "Nature" shows that a kind of molecular evidence has been found-the complex relationship between diet, gut microbiota and immune function The interaction provides a unified explanation
.
It is determined that the metabolic decomposition of dietary amino acids in the mouse intestine triggers the immune signal cascade reaction, in which branched-chain amino acids are absorbed by the intestinal microbe Bacteroides fragilis and converted into glycolipid molecules that also have branched chains by specific enzymes
.
Finally, the Harvard team proved that the branched-chain lipid molecules synthesized in the laboratory induced NK T cells to release the immune signal chemical IL-2
.
The use of branched-chain glycolipid molecules to treat mice with ulcerative colitis has shown good results
.
This discovery provides hope for these NK T cell-mediated inflammatory diseases.
NK T cells are the immune cells that are eventually activated by the molecules produced by this microorganism to control inflammation in the colon of mice.
This study can also be confirmed in humans.
, Will help design small molecule treatments, thereby enhancing the intestinal tract and overall immunity
.
"What you eat is what you eat
.
" This "cliche" has been used for hundreds of years to illustrate the connection between diet and health
.
Now, an international research team has found molecular evidence for this concept, demonstrating how diet ultimately affects immunity through the gut microbiota
.
This study conducted in mice showed that the food consumed by the animal triggers the release of a specific by-product of intestinal microbial metabolism, which in turn regulates the animal's intestinal immunity
.
Recently, the findings published in the journal Nature provide a unified explanation for the complex interactions between diet, gut microbiota, and immune function
.
This is the result of a collaboration between scientists from Harvard Medical School, Brigham and Women's Hospital, Seoul National University, and Monash University in Australia
.
The researchers published an article titled "Host immunomodulatory lipids created by symbionts from dietary amino acids": The experiment pinpointed a microbial molecule whose synthesis and release are affected by the host's diet
.
This molecule in turn stimulates the activation and signal transmission of a subset of cells called natural killer (NK) T cells, which are involved in immune regulation and are involved in a range of inflammatory states
.
Dennis Kasper, professor of immunology at the Blavatnik Institute at Harvard Medical School and senior author of the study, said that although scientists have long speculated that diet plays an important role in immune health, this new study sheds light on the precise molecular level behind this interaction.
United
.
Kasper said: "We have shown how diet affects the immune system through microbial mediators in the intestine.
This is a very significant example of the role of the diet-microbe-immune triad
.
What
this study really does is to provide a A step-by-step approach from beginning to end to explain how and why these three effects, and how diet ultimately affects the immune system
.
" The researchers said that if it is confirmed in large animals, it will eventually be confirmed in humans.
This discovery It will help design small molecule treatments to enhance the intestinal tract and overall immunity
.
Sungwhan Oh, the principal investigator of the Brigham Center for Experimental Treatment and Reperfusion Injury, a former postdoctoral researcher in Kasper's laboratory, and the first author of the study, said: "The molecules produced by gut microbes have huge structural diversity
.
We use microbes and Chemical tools to clarify how these molecules are synthesized by gut bacteria and their role in the host’s gut
.
Our findings have produced fascinating insights into the microbiome, diet, and immune function, and provided interesting clues.
Explain how to use molecules made by our internal neighbors to design therapies
.
"In a series of experiments, the research team determined the immune signal cascade triggered by the metabolic breakdown of dietary amino acids in the mouse intestine
.
This multi-step approach starts when an animal eats food containing branched-chain amino acids, which are named after the dendritic structure of one molecular chain
.
The branched-chain amino acids are then absorbed by the gut microbe B.
fragilis and converted by a specific enzyme into glycolipid molecules that also have branched chains
.
Bacteroides fragilis then releases branched-chain molecules, which are discovered and picked up by a class of immune signaling cells called antigen-presenting cells.
In turn, it induces NK T cells to exercise immunity by up-regulating inflammation control genes and immunomodulatory chemicals.
Adjust the response
.
It is worth noting that experiments have proved that it is the branches of the chain structure that trigger the cascade
.
The linear form of this molecule did not produce the same effect
.
In addition, the research team found that Bacteroides fragilis changed the structure of its metabolized glycolipid molecules, enabling it to better bind to receptors on specific immune cells and initiate a signal cascade, which ultimately leads to a down-regulation of inflammation
.
The study also showed that each of the three different branched-chain amino acids ingested by mice produced slightly different structural changes to bacterial lipid molecules, resulting in different patterns of binding to immune cells
.
Co-researcher Seung Bum Park, professor of chemistry at Seoul National University, synthesized 23 different forms of microorganisms and conducted experiments by a research team at Harvard University
.
They created immunomodulatory molecules to determine how each microorganism interacts with immune cells that regulate inflammation
.
Experiments by the Harvard team showed that the branched-chain lipid molecules synthesized in the laboratory induced NK T cells to release the immune signal chemical IL-2, while the linear-chain lipid molecules made in the laboratory did not
.
Therefore, NK T cells are activated to induce the expression of genes that regulate immunity, rather than the expression of genes that drive inflammation
.
Jamie Rossjohn, professor of biochemistry and molecular biology at the Monash Institute of Biomedical Discovery, Australia, used structural biology methods to clarify how lipid structures bind to antigen-presenting cells
.
Antigen-presenting cells are a type of immune cell, and NK T cells can produce anti-inflammatory chemicals
.
In the last step, the researchers used branched-chain glycolipid molecules to treat mice with ulcerative colitis
.
Animals treated with branched-chain molecules performed much better than untreated animals
.
Not only did they gain weight, but when the researchers examined the mice’s intestinal cells under a microscope, they found that these cells also had mild signs of colon inflammation
.
In summary, these experiments provide a structural and molecular explanation for the previously observed anti-inflammatory effects of this type of glycolipid produced by the gut microbe Bacteroides fragilis
.
Rossjohn said: "This research provides a good example of interdisciplinary discovery research, and aims to answer a major question in biomedical science, namely how the interaction between diet and microbiota regulates the immune system
.
" 2014 Kasper and colleagues published a study showing that glycolipid molecules released by Bacteroides fragilis have anti-inflammatory effects on the intestines and protect mice from colitis, but scientists don’t know how these molecules are produced by microorganisms.
, There is no specific structural feature of glycolipid that confers anti-inflammatory effects
.
The current research answers this question and proves that the glycolipid molecules produced by this particular organism are branched.
It is this branched structure that allows them to bind to immune cells in a way that inhibits the pro-inflammatory signals of these cells
.
Kasper said: "Our new research shows that the branching of the lipid structure induces a very different response-the branching of this structure induces an anti-inflammatory response, not a pro-inflammatory response
.
" The researchers said this The discovery provides hope for these NK T cell-mediated inflammatory diseases, which can one day be treated with microbial molecules made in the laboratory to inhibit inflammation
.
Kasper said the exact function of NK T cells is unclear
.
NK T cells are immune cells that are ultimately activated by molecules produced by this microorganism to control inflammation in the mouse colon
.
However, considering that these cells are distributed in the human gastrointestinal tract and lungs, as well as in the liver and spleen, they may play an important role in immune regulation
.
Previous studies have shown that these cells may be involved in a series of inflammations, including ulcerative colitis, and may be involved in airway inflammation such as asthma
.
Kasper also said: "We will never be able to isolate enough immunomodulatory molecules from bacteria for treatment, but the beauty of this technology is that we can now synthesize them in the laboratory.
.
Our idea is that we will have a drug that can regulate inflammation inside and outside the colon
.
"Co-authors include T.
Praveena, Heebun Song, Ji Sun Yoo, Da Jung Jung Jung, Deniz Erturk Hasdemir, Yoon Soo Hwang, ChangWon Lee, Jérôme Le Nours, Hyunsoo Kim, Jesang Lee and Richard Blumberg
.
Reference: https:/ /medicalxpress.
com/news/2021-11-mice-diet-immune-function-gut.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment plans
.
If you need health guidance, please go to a regular hospital
.
Recommendation·Activity New diagnostic technology clinical application Salon hot·Article Vaccine research and development [Nature] Pharmaceutical giant Sanofi and others are leading the development of protein vaccines, and the era of protein-based COVID-19 vaccines may be coming soon! Cancer treatment [Nature sub-Journal] Large-scale study of 480,000 people: In the face of extremely lethal liver cancer and chronic liver disease, scientists have confirmed that whole grains and dietary fiber can greatly reduce the risk of death! Cancer treatment [eLife] Can infrared fingerprints help detect cancer? The prospects are bright! Medical Research [Science Sub-Journal] Cupping + New Coronary DNA Vaccine = Immune Response × 100, Chinese scientists combined ancient and modern medicine and invented a new transfection method! New Coronavirus [Science Breakthrough] The Nobel Prize Female Scientist has developed a new system tool that focuses on a rarely noticed mutation in Delta, revealing why Delta is so contagious? Gene Sequencing【BMJ】Benefits all mankind! The pain of rare disease diagnosis will become history, and whole-genome sequencing is an inevitable trend in medical development! Genetic disease treatment 【Science】The era of RNA drugs has arrived, and the future is boundless! Soon it may bring new insights into cancer treatment [AACR sub-Journal] for patients with rarer genetic diseases! Gastric Cancer Atlas brings new treatment strategies!
Please indicate the source for reprinting.
Author: Daisy Guide: Recently, a study published in "Nature" shows that a kind of molecular evidence has been found-the complex relationship between diet, gut microbiota and immune function The interaction provides a unified explanation
.
It is determined that the metabolic decomposition of dietary amino acids in the mouse intestine triggers the immune signal cascade reaction, in which branched-chain amino acids are absorbed by the intestinal microbe Bacteroides fragilis and converted into glycolipid molecules that also have branched chains by specific enzymes
.
Finally, the Harvard team proved that the branched-chain lipid molecules synthesized in the laboratory induced NK T cells to release the immune signal chemical IL-2
.
The use of branched-chain glycolipid molecules to treat mice with ulcerative colitis has shown good results
.
This discovery provides hope for these NK T cell-mediated inflammatory diseases.
NK T cells are the immune cells that are eventually activated by the molecules produced by this microorganism to control inflammation in the colon of mice.
This study can also be confirmed in humans.
, Will help design small molecule treatments, thereby enhancing the intestinal tract and overall immunity
.
"What you eat is what you eat
.
" This "cliche" has been used for hundreds of years to illustrate the connection between diet and health
.
Now, an international research team has found molecular evidence for this concept, demonstrating how diet ultimately affects immunity through the gut microbiota
.
This study conducted in mice showed that the food consumed by the animal triggers the release of a specific by-product of intestinal microbial metabolism, which in turn regulates the animal's intestinal immunity
.
Recently, the findings published in the journal Nature provide a unified explanation for the complex interactions between diet, gut microbiota, and immune function
.
This is the result of a collaboration between scientists from Harvard Medical School, Brigham and Women's Hospital, Seoul National University, and Monash University in Australia
.
The researchers published an article titled "Host immunomodulatory lipids created by symbionts from dietary amino acids": The experiment pinpointed a microbial molecule whose synthesis and release are affected by the host's diet
.
This molecule in turn stimulates the activation and signal transmission of a subset of cells called natural killer (NK) T cells, which are involved in immune regulation and are involved in a range of inflammatory states
.
Dennis Kasper, professor of immunology at the Blavatnik Institute at Harvard Medical School and senior author of the study, said that although scientists have long speculated that diet plays an important role in immune health, this new study sheds light on the precise molecular level behind this interaction.
United
.
Kasper said: "We have shown how diet affects the immune system through microbial mediators in the intestine.
This is a very significant example of the role of the diet-microbe-immune triad
.
What
this study really does is to provide a A step-by-step approach from beginning to end to explain how and why these three effects, and how diet ultimately affects the immune system
.
" The researchers said that if it is confirmed in large animals, it will eventually be confirmed in humans.
This discovery It will help design small molecule treatments to enhance the intestinal tract and overall immunity
.
Sungwhan Oh, the principal investigator of the Brigham Center for Experimental Treatment and Reperfusion Injury, a former postdoctoral researcher in Kasper's laboratory, and the first author of the study, said: "The molecules produced by gut microbes have huge structural diversity
.
We use microbes and Chemical tools to clarify how these molecules are synthesized by gut bacteria and their role in the host’s gut
.
Our findings have produced fascinating insights into the microbiome, diet, and immune function, and provided interesting clues.
Explain how to use molecules made by our internal neighbors to design therapies
.
"In a series of experiments, the research team determined the immune signal cascade triggered by the metabolic breakdown of dietary amino acids in the mouse intestine
.
This multi-step approach starts when an animal eats food containing branched-chain amino acids, which are named after the dendritic structure of one molecular chain
.
The branched-chain amino acids are then absorbed by the gut microbe B.
fragilis and converted by a specific enzyme into glycolipid molecules that also have branched chains
.
Bacteroides fragilis then releases branched-chain molecules, which are discovered and picked up by a class of immune signaling cells called antigen-presenting cells.
In turn, it induces NK T cells to exercise immunity by up-regulating inflammation control genes and immunomodulatory chemicals.
Adjust the response
.
It is worth noting that experiments have proved that it is the branches of the chain structure that trigger the cascade
.
The linear form of this molecule did not produce the same effect
.
In addition, the research team found that Bacteroides fragilis changed the structure of its metabolized glycolipid molecules, enabling it to better bind to receptors on specific immune cells and initiate a signal cascade, which ultimately leads to a down-regulation of inflammation
.
The study also showed that each of the three different branched-chain amino acids ingested by mice produced slightly different structural changes to bacterial lipid molecules, resulting in different patterns of binding to immune cells
.
Co-researcher Seung Bum Park, professor of chemistry at Seoul National University, synthesized 23 different forms of microorganisms and conducted experiments by a research team at Harvard University
.
They created immunomodulatory molecules to determine how each microorganism interacts with immune cells that regulate inflammation
.
Experiments by the Harvard team showed that the branched-chain lipid molecules synthesized in the laboratory induced NK T cells to release the immune signal chemical IL-2, while the linear-chain lipid molecules made in the laboratory did not
.
Therefore, NK T cells are activated to induce the expression of genes that regulate immunity, rather than the expression of genes that drive inflammation
.
Jamie Rossjohn, professor of biochemistry and molecular biology at the Monash Institute of Biomedical Discovery, Australia, used structural biology methods to clarify how lipid structures bind to antigen-presenting cells
.
Antigen-presenting cells are a type of immune cell, and NK T cells can produce anti-inflammatory chemicals
.
In the last step, the researchers used branched-chain glycolipid molecules to treat mice with ulcerative colitis
.
Animals treated with branched-chain molecules performed much better than untreated animals
.
Not only did they gain weight, but when the researchers examined the mice’s intestinal cells under a microscope, they found that these cells also had mild signs of colon inflammation
.
In summary, these experiments provide a structural and molecular explanation for the previously observed anti-inflammatory effects of this type of glycolipid produced by the gut microbe Bacteroides fragilis
.
Rossjohn said: "This research provides a good example of interdisciplinary discovery research, and aims to answer a major question in biomedical science, namely how the interaction between diet and microbiota regulates the immune system
.
" 2014 Kasper and colleagues published a study showing that glycolipid molecules released by Bacteroides fragilis have anti-inflammatory effects on the intestines and protect mice from colitis, but scientists don’t know how these molecules are produced by microorganisms.
, There is no specific structural feature of glycolipid that confers anti-inflammatory effects
.
The current research answers this question and proves that the glycolipid molecules produced by this particular organism are branched.
It is this branched structure that allows them to bind to immune cells in a way that inhibits the pro-inflammatory signals of these cells
.
Kasper said: "Our new research shows that the branching of the lipid structure induces a very different response-the branching of this structure induces an anti-inflammatory response, not a pro-inflammatory response
.
" The researchers said this The discovery provides hope for these NK T cell-mediated inflammatory diseases, which can one day be treated with microbial molecules made in the laboratory to inhibit inflammation
.
Kasper said the exact function of NK T cells is unclear
.
NK T cells are immune cells that are ultimately activated by molecules produced by this microorganism to control inflammation in the mouse colon
.
However, considering that these cells are distributed in the human gastrointestinal tract and lungs, as well as in the liver and spleen, they may play an important role in immune regulation
.
Previous studies have shown that these cells may be involved in a series of inflammations, including ulcerative colitis, and may be involved in airway inflammation such as asthma
.
Kasper also said: "We will never be able to isolate enough immunomodulatory molecules from bacteria for treatment, but the beauty of this technology is that we can now synthesize them in the laboratory.
.
Our idea is that we will have a drug that can regulate inflammation inside and outside the colon
.
"Co-authors include T.
Praveena, Heebun Song, Ji Sun Yoo, Da Jung Jung Jung, Deniz Erturk Hasdemir, Yoon Soo Hwang, ChangWon Lee, Jérôme Le Nours, Hyunsoo Kim, Jesang Lee and Richard Blumberg
.
Reference: https:/ /medicalxpress.
com/news/2021-11-mice-diet-immune-function-gut.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment plans
.
If you need health guidance, please go to a regular hospital
.
Recommendation·Activity New diagnostic technology clinical application Salon hot·Article Vaccine research and development [Nature] Pharmaceutical giant Sanofi and others are leading the development of protein vaccines, and the era of protein-based COVID-19 vaccines may be coming soon! Cancer treatment [Nature sub-Journal] Large-scale study of 480,000 people: In the face of extremely lethal liver cancer and chronic liver disease, scientists have confirmed that whole grains and dietary fiber can greatly reduce the risk of death! Cancer treatment [eLife] Can infrared fingerprints help detect cancer? The prospects are bright! Medical Research [Science Sub-Journal] Cupping + New Coronary DNA Vaccine = Immune Response × 100, Chinese scientists combined ancient and modern medicine and invented a new transfection method! New Coronavirus [Science Breakthrough] The Nobel Prize Female Scientist has developed a new system tool that focuses on a rarely noticed mutation in Delta, revealing why Delta is so contagious? Gene Sequencing【BMJ】Benefits all mankind! The pain of rare disease diagnosis will become history, and whole-genome sequencing is an inevitable trend in medical development! Genetic disease treatment 【Science】The era of RNA drugs has arrived, and the future is boundless! Soon it may bring new insights into cancer treatment [AACR sub-Journal] for patients with rarer genetic diseases! Gastric Cancer Atlas brings new treatment strategies!
