Don't look at these massive studies of human healthy gut microbiome NCS

August 30, 2019 / BIOON / - in recent years, the research on intestinal microorganisms has become more and more popular More and more in-depth research has gradually revealed many secrets of intestinal microorganisms More and more studies have found that intestinal microorganisms are closely related to human health In this paper, we reviewed the recent NCS studies on gut microbes and health, and shared them with you 【1】 Cell: shock! In a new study, researchers from MD Anderson Cancer Research Center at the University of Texas in the United States found that a key difference between a small number of long-term survivors of pancreatic cancer and many patients with pancreatic cancer who failed to respond to all treatments was the bacteria in their tumors The community stimulates or suppresses the immune response The results are published in the August 8, 2019 issue of cell Using 16S rRNA gene sequencing, the researchers found that the bacterial diversity of long-term survivors far exceeded that of short-term survivors The median survival of patients from the MD Anderson cohort was 9.66 years for those with high diversity and 1.66 years for those with low diversity This diversity result has nothing to do with other factors such as previous therapies, body mass index (BMI) and antibiotic use, which makes it a predictor of patient survival and points out the potential importance of tumor microbiome in cancer progression Immunohistochemistry showed that the tumors of the long-term survivors in the two cohorts had higher T cell density, including CD8 positive killer T cells, which was consistent with the previous research results that the long-term survivors had stronger immune response The researchers compared bacteria in the intestines, tumors, and adjacent tissues of three surgical patients They found that the intestinal microbiome accounts for about 25% of the tumor microbiome, but does not exist in normal adjacent tissues, indicating that bacteria in the intestinal tract can be colonized in pancreatic tumors The researchers transplanted fecal flora from patients with advanced cancer into mice and found that the donor microbiome accounted for about 5% of the resulting tumor microbiome, but 70% of the total tumor microbiome had been changed Next, they transplanted faecal flora from patients with advanced pancreatic cancer, patients who had survived for more than five years without signs of disease, and healthy controls into mice Five weeks after tumor production, mice receiving fecal microbiome transplants from patients with advanced pancreatic cancer had larger tumors, while mice receiving fecal microbiome transplants from long-term survivors had a 70% reduction in tumor size on average, and mice receiving fecal microbiome transplants from healthy controls had a 50% reduction in tumor size on average Immunoassay showed significantly higher numbers of CD8 positive T cells and greater activation of CD8 positive T cells in mice receiving fecal flora transplantation from long-term survivors compared with the other two groups Mice receiving fecal microbiota from patients with advanced pancreatic cancer had increased regulatory T cells and myelogenous suppressor cells, both of which inhibited the immune response To assess whether FMT's effect depends on the immune system, the researchers removed T cells from a group of mice that received fecal microbiota transplants from long-term survivors, completely blocking the antitumor effect of FMT 【2】 Nature breakthrough: intestinal microorganisms may affect the process of ALS doi: 10.1038/s41586-019-1443-5 research conducted by researchers of Weizmann Institute of Science in mice found that intestinal microorganisms (collectively referred to as intestinal microflora) may affect the process of ALS, also known as lugaretian's disease The researchers found that the progress of a disease similar to ALS slows down after mice received some intestinal microbial strains or substances that are known to be secreted by these microorganisms The preliminary results showed that the discovery of the regulatory function of this bacterial group may be applicable to ALS patients The relevant research results were published in nature recently Scientists have shown in a series of experiments that the symptoms of an ALS like disease worsen when most of its microbiota is removed with broad-spectrum antibiotics in transgenic mice In addition, the scientists also found that it is very difficult to cultivate these ALS prone mice in sterile conditions, because these mice are difficult to survive in sterile environment In conclusion, these results suggest a potential link between changes in microbiota and accelerated disease development in mice genetically predisposed to ALS Next, using advanced computational methods, scientists characterized the composition and function of the microbiome in mice prone to ALS, and compared them with normal mice They identified 11 microbial strains that changed as the disease progressed in mice prone to ALS, even before the mice developed significant ALS symptoms When the scientists isolated these microbial strains and gave them to mice prone to ALS one by one in the form of probiotic like supplements after antibiotic treatment, some of them had a significant negative impact on this ALS like disease But a strain called akkermansia muciniphila significantly slowed down the progression of disease in mice and prolonged their survival time To reveal how the bacteria produced this effect, scientists examined thousands of small molecules secreted by intestinal microbes They focused on a molecule called nicotinamide (NAM): after antibiotic treatment, the levels of nicotinamide in the blood and cerebrospinal fluid of mice prone to ALS decreased, while after administration of akkermansia, which secretes the molecule, the levels of nicotinamide increased In order to confirm that Nam is indeed a kind of microbial secretory molecule that can block the progress of ALS, scientists have continuously injected Nam into mice prone to ALS The clinical condition of these mice improved significantly Detailed studies of gene expression in their brains have shown that Nam improves the function of their motor neurons 【3】 Two science papers pointed out that the new therapeutic food can promote the healthy development of intestinal microbiome in malnourished children Doi: 10.1126/science.aau4732, 10.1126/science.aau4735 An interdisciplinary research team from the St Louis School of medicine, University of Washington, and the International Center for diarrhoeal disease research in Bangladesh has taken a new approach to address the pressing global health problem of child malnutrition Their approach focuses on selectively promoting the healthy development of key growth promoting gut microorganisms through the use of ingredients present in affordable, culturally acceptable foods Their research supports the idea that the healthy growth of infants and children is closely related to the healthy development of their intestinal microbiota after birth In two papers published in science on July 12, 2019, these new therapeutic foods directed by intestinal microbiome, developed by Washington University and Bangladesh International Center for diarrhea research, come from their earlier research on the development of intestinal microbiome in healthy children in Bangladesh A few years ago, they found that malnourished children have immature gut microbiomes - those that look younger than their age matched healthy peers Ahmed points out that a few years ago they found that conventional therapeutic foods failed to repair this immaturity in the malnourished children they had treated The Gordon team then transplanted the immature intestinal microbiota from malnourished children and the normally mature intestinal microbiota from healthy children into mice that were normally kept in sterile conditions The results showed that the immature intestinal microflora was related to the weight loss, bone development defect, metabolism and immune function abnormality of mice These findings provide early evidence that failure to form a normal gut microbiome may be the cause of malnutrition, not the consequence of malnutrition In the first of these two papers, the co authors are Dr Jeanette L Gehrig, Dr siddarth Venkatesh and Hao Wei Chang (who are all members of Gordon's Lab) describes how they first used sterile mice, then sterile piglets, and transplanted members of the intestinal microbiome from Bangladeshi children into these sterile mice and pigs to screen a range of diets made up of ingredients from complementary foods used in Bangladesh They developed the microbiome directed comprehensive food prototype, which can repair and transplant the immature intestinal microflora from malnourished Bangladeshi children in these two animal models, and improve the health of these animals The researchers then tested the food prototype in accordance with the double-blind controlled feeding study described above In the second paper, the first author, Dr Arjun S Raman, a member of Gordon laboratory, described a method for analyzing how economic fluctuations affect complex and dynamic financial markets, which was originally developed in the field of economic physics, and developed new computational methods This method provides a new general method to characterize the structure of human intestinal microflora - their normal development, how they are disturbed in the state of malnutrition and other diseases, and how they respond to treatment interventions designed to repair them 【4】 Science: gut microbes are able to digest our drug doi: 10.1126/science.aau6323 in a recent = study, researchers at the University of California, San Francisco, described the first concrete example of how microbiomes interfere with the expected effects of drugs They focused on L-dopa, the main treatment for Parkinson's disease, and they identified which of the trillions of bacteria are responsible for the degradation of drugs and how to prevent this microbial interference Using the Human Microbiome Project as a reference, maini Rekdal and his team looked through bacterial DNA to find out which gut microbes had genes that encode enzymes similar to those found in them There are several microorganisms that meet their criteria, only one of which is Enterococcus faecalis (Enterococcus faecalis), which metabolizes all L-dopa Through this discovery, the team provided the first strong evidence that Enterococcus faecalis and bacterial enzymes (PLP dependent tyrosine decarboxylase or tyrdc) were associated with L-dopa metabolism Even though human and bacterial enzymes perform exactly the same chemical reactions, bacteria look a little different Maini Rekdal speculated that carbidopa might not be able to penetrate microbial cells, or that slight structural differences might prevent the drug from interacting with bacterial enzymes But the reason may not matter Balskus and her team have found a molecule that inhibits bacterial enzymes "The molecule shuts down this unnecessary bacterial metabolism without killing the bacteria," maini Rekdal said This and similar compounds can provide a starting point for the development of new drugs to improve the therapeutic effect of levodopa in patients with Parkinson's disease 【5】 One nature and one nature medicine point out that human microbiome is related to prediabetes, inflammatory bowel disease and premature delivery