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Click [Medical Formula] Paying attention to our gut microbiota is an important factor in the occurrence and development of many diseases.
For example, the occurrence of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) is closely related to changes in the gut microbiota.
Therefore, using intestinal microbiota transplantation (FMT) to reshape the intestinal microbiota to restore the normal interaction between the host and the microbiota is a promising therapeutic strategy.
More and more studies have found that FMT has shown good efficacy in the treatment of inflammatory bowel disease and irritable bowel syndrome.
FMT usually uses frozen capsules, enema, colonoscopy or duodenal perfusion to transfer the fecal microbiota of healthy donors to diseased recipients to achieve the therapeutic effect.
Although it looks simple and rough, it is currently the only microbial-based treatment that can transplant a complex microecosystem into the intestine.
Although FMT has been used clinically for many years, there are still many unknown factors for its exact mode of action and long-term safety and effectiveness.
In addition, the role of intestinal microbiota in different diseases is different, indicating that there is still a need to select donors and FMT operating procedures in accordance with the disease situation.
So what diseases can FMT be applied to, and how does it work? Next, take a few high-scoring articles as examples to describe in detail the application and design of FMT in the treatment of human diseases.
1.
JAMA 2019: Patients with ulcerative colitis (UC) relief after 8 weeks of FMT.
Experimental design: (1) Among 73 subjects with ulcerative colitis, 35 received autologous FMT randomly and 38 randomly received donor FMT (2) The subjects undergo FMT through colonoscopy for the first time, and then receive 2 enema within 7 days; (3) In the 8th week, evaluate the effect of FMT treatment, perform colonoscopy and evaluate the colitis activity index; (4) Follow up for 12 months.Experimental results: (1) 12 subjects completed donor FMT, 3 subjects completed autologous FMT, and 5 subjects after donor FMT continued to relieve symptoms after 12 months; (2) Donor There were 3 serious adverse events in the FMT group and 2 serious adverse events in the autologous FMT group.
2.
Science 2020: FMT can promote the response of immunotherapy patients with refractory melanoma.
Experimental design: (1) 10 patients cleared the native intestinal flora in the body within 72 hours, including oral vancomycin (500mg), neomycin Combination of gluten (100mg) and polyethylene glycol (PEG, the last 15h) solution; (2) The recipient can suppress intestinal flora through colonoscopy and oral stool capsule at the same time; (3) Take it to the patient on the 12th day FMT capsules to maintain the intestinal flora; (4) Two days later, the recipient will be given anti-PD-1 drug (nivolumab) therapy; (5) The last capsule FMT combined with anti-PD-1 drug therapy will be repeated every 14 days for a total of 6 (6) Assess the treatment effect, and the recipients with clinical immune response and remission continue to be treated with anti-PD-1 drugs alone.
Experimental results: (1) The safety of FMT combined with anti-PD-1 agents was good, and 3 patients had a clinical response; (2) Fecal bacterial transplantation (FMT) changed the recipient’s intestinal flora, which is conducive to immunotherapy.
Increased Rongococcus and decreased bifidobacteria that promote immune tolerance, but the bacterial groups and metabolic functions that are significantly related to clinical response have not been identified; (3) FMT therapy and immune cell infiltration and genes in the intestinal and tumor microenvironment The improvement of expression profile is related.
3.
Gastroenterology 2021: The long-term safety experiment design of FMT in the treatment of recurrent Clostridium difficile infection (CDI): (1) Include 609 rCDI patients undergoing FMT through colonoscopy or enema; (2) 1 week, 1 week after FMT Follow-up for months, 6 months and 1 year.
At each time point, a questionnaire will be conducted on the patients to ask about symptoms (diarrhea, constipation, urgency, cramps), duration, relief, new symptoms, antibiotic use, and Diffuse Shuttle Bacteria detection.
If there is a recurrence, ask the patient about the treatment and the resolution of the symptoms; (3) 447 of them will be followed up for more than 2 years.
Experimental results: (1) During the 1-year follow-up period, more than 60% of patients had diarrhea, less than 33% of patients had constipation, and 9.
5% of patients had recurrence of CDI; (2) Patients with IBD, dialysis-dependent nephropathy, and multiple FMT The risk of diarrhea is higher, and the risk of constipation in female patients is higher, while the risk of constipation in IBD patients is lower; (3) During the long-term follow-up, 188 patients developed 73 new symptoms, of which 13% had gastrointestinal diseases and 10% of their body weight Increase, 11.
8% of new infections.
A number of studies have confirmed that FMT has a good curative effect in the treatment of recurrent CDI and ulcerative colitis, but the curative effect on allergic diseases, inflammatory bowel disease (CD) and autoimmune diseases remains to be confirmed.
CDI is mainly a disease driven by pathogenic microorganisms, which is characterized by the loss of the barrier function of the intestinal microbiota, while FMT can reset and restore the richness and diversity of the intestinal flora to prevent the colonization and pathogenicity of Clostridium difficile Sex.
In a study for the treatment of inflammatory bowel disease (IBD), the combination of corticosteroids and FMT can relieve patients' symptoms for a long time.
In the study of using FMT to treat irritable bowel syndrome (IBS), 2 items showed a significant improvement in the condition, while the other 3 items had no obvious effect.
Of course, this may be related to factors such as the characteristics of patients with IBS, the condition of the donor, the route of administration, and the number of FMTs.
A domestic meta-analysis found that among 26 FMT clinical studies, 3/4, 1/4, and 1/2 of the studies reported that fecal bacteria transplantation has significant effects on liver disease, metabolic syndrome/obesity, and antibiotic resistance.
Clinical efficacy.
In the process of treating complex diseases through FMT, we must understand that the intestinal microbiota is only one of the many factors that cause diseases, and its weight in the pathology and physiology of different diseases is different.
At the same time, the choice of donor for FMT is very important.
For example, there is a study transplanting the fecal flora of a healthy young donor who loves sports, does not smoke, and was born naturally to IBS patients, and the condition has been significantly improved.
Therefore, the abundance of intestinal flora and the existence of health-related species are important factors that need to be considered when selecting a donor.
Studies have shown that transplantation of whole intestinal flora is more accurate than transplantation of colon/colon flora.
Of course, before performing FMT, the condition of the recipient should also be taken into consideration.
Studies have shown that UC patients with improved symptoms after FMT have higher intestinal flora and Candida abundance than before FMT.
In addition, studies have reported that the failure of FMT in the treatment of CD is related to the enrichment of Klebsiella, Actinomycetes and Haemophilus in the intestinal tract of patients.
These studies indicate that the intestinal flora of the recipient at baseline may affect the effect and clinical outcome of FMT.
If microorganisms related to the efficacy of FMT are confirmed, they can help different types of patients choose targeted treatment strategies.
Therefore, long-term monitoring of microorganisms that change before and after FMT treatment is very necessary.
At present, the causal relationship and mechanism between bacterial flora changes and diseases are not clear, and it is difficult to determine the time and dose of FMT.
The response of the same patient to FMT may change over time.
There may also be harmful strains in the donor flora, which may cause infection and infectious diseases.
A domestic study reviewed the development and safety of FMT in the past 20 years and found that serious adverse events occurred in patients with impaired intestinal mucosal barrier.
Therefore, it is still necessary to further clarify the efficacy of FMT and formulate individualized donor-recipient pairing schemes to ensure safe and stable treatment.
In conclusion, in the future FMT research design, it is necessary to formulate precision medical strategies and carry out targeted intervention treatment for each patient.
First of all, suitable FMT donors and recipients should be determined based on clinical, microbiological, immune and metabolic parameters in blood and feces.
At the same time, the intestinal microbiota of the donors and recipients need to be accurately characterized to determine the relationship between disease control and FMT.
Influencing factors related to efficacy.
Secondly, the FMT process is designed according to the characteristics of the recipient, including the characteristics of the donor, treatment methods and auxiliary medical care, to ensure the efficacy of FMT.
After FMT, clinical parameters, immune response and microbial composition should also be specifically monitored.
At present, FMT has been extensively explored in gastrointestinal inflammation, metabolic diseases, cardiovascular diseases, and nervous system.
At the same time, it has also made certain breakthroughs in microbial targeted intervention and auxiliary tumor immunotherapy.
However, the effectiveness of FMT in many studies varies.
This also needs to be more refined and personalized in the future FMT-related research and design for precision medicine.
The application of FMT technology is now on the verge of a new era, and there are still vast unknown areas that we need to explore.
I hope this article will help you in the research of intestinal flora, the application of FMT, and the design of related topics and fund applications.
References 1.
Eusebi LH, Telese A, Marasco G, et al.
Gastric cancer prevention strategies: A global perspective.
J Gastroenterol Hepatol, 2020.
2.
Costello SP, Hughes PA, Waters O, et al.
Effect of Fecal Microbiota Transplantation on 8 -Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.
JAMA, 20193.
Baruch EN, Youngster I, Ben-Betzalel G, et al.
Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.
Science, 2020.
4.
Saha S , Mara K, Pardi DS, et al.
Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.
Gastroenterology, 2021.
END Call for contributions "Medical Formula" is now officially open to fans! The content must be originally published and related to scientific research.
Once adopted, a generous reward (300-2000 yuan) will be given.
Please stamp for details.
"Medical side" has always been committed to serving "medical people", pushing the most cutting-edge and most valuable original clinical and scientific research articles to clinicians and scientific researchers.
The medical department has launched "Laboratory Basics", "SCI Writing Skills", "Document Intensive Reading and Analysis", "Easy Learning of Medical English", "National Natural Science Foundation of China", "Clinical Data Mining", "Gene Data Mining", "R Language Tutorial", "Medical Statistics", "Minimally Invasive Animal Experiment Training" and many other special courses, if you need to know the detailed tweets of the courses, you can follow the "Medical Party" public account and click "Exquisite Topics" to enter the Tencent classroom: https://medfun .
ke.
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com NetEase Cloud Classroom: http://study.
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com/u/ykt1467466791112 Customer Service Tel: 15821255568 Customer Service WeChat: yixuefang1234
For example, the occurrence of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) is closely related to changes in the gut microbiota.
Therefore, using intestinal microbiota transplantation (FMT) to reshape the intestinal microbiota to restore the normal interaction between the host and the microbiota is a promising therapeutic strategy.
More and more studies have found that FMT has shown good efficacy in the treatment of inflammatory bowel disease and irritable bowel syndrome.
FMT usually uses frozen capsules, enema, colonoscopy or duodenal perfusion to transfer the fecal microbiota of healthy donors to diseased recipients to achieve the therapeutic effect.
Although it looks simple and rough, it is currently the only microbial-based treatment that can transplant a complex microecosystem into the intestine.
Although FMT has been used clinically for many years, there are still many unknown factors for its exact mode of action and long-term safety and effectiveness.
In addition, the role of intestinal microbiota in different diseases is different, indicating that there is still a need to select donors and FMT operating procedures in accordance with the disease situation.
So what diseases can FMT be applied to, and how does it work? Next, take a few high-scoring articles as examples to describe in detail the application and design of FMT in the treatment of human diseases.
1.
JAMA 2019: Patients with ulcerative colitis (UC) relief after 8 weeks of FMT.
Experimental design: (1) Among 73 subjects with ulcerative colitis, 35 received autologous FMT randomly and 38 randomly received donor FMT (2) The subjects undergo FMT through colonoscopy for the first time, and then receive 2 enema within 7 days; (3) In the 8th week, evaluate the effect of FMT treatment, perform colonoscopy and evaluate the colitis activity index; (4) Follow up for 12 months.Experimental results: (1) 12 subjects completed donor FMT, 3 subjects completed autologous FMT, and 5 subjects after donor FMT continued to relieve symptoms after 12 months; (2) Donor There were 3 serious adverse events in the FMT group and 2 serious adverse events in the autologous FMT group.
2.
Science 2020: FMT can promote the response of immunotherapy patients with refractory melanoma.
Experimental design: (1) 10 patients cleared the native intestinal flora in the body within 72 hours, including oral vancomycin (500mg), neomycin Combination of gluten (100mg) and polyethylene glycol (PEG, the last 15h) solution; (2) The recipient can suppress intestinal flora through colonoscopy and oral stool capsule at the same time; (3) Take it to the patient on the 12th day FMT capsules to maintain the intestinal flora; (4) Two days later, the recipient will be given anti-PD-1 drug (nivolumab) therapy; (5) The last capsule FMT combined with anti-PD-1 drug therapy will be repeated every 14 days for a total of 6 (6) Assess the treatment effect, and the recipients with clinical immune response and remission continue to be treated with anti-PD-1 drugs alone.
Experimental results: (1) The safety of FMT combined with anti-PD-1 agents was good, and 3 patients had a clinical response; (2) Fecal bacterial transplantation (FMT) changed the recipient’s intestinal flora, which is conducive to immunotherapy.
Increased Rongococcus and decreased bifidobacteria that promote immune tolerance, but the bacterial groups and metabolic functions that are significantly related to clinical response have not been identified; (3) FMT therapy and immune cell infiltration and genes in the intestinal and tumor microenvironment The improvement of expression profile is related.
3.
Gastroenterology 2021: The long-term safety experiment design of FMT in the treatment of recurrent Clostridium difficile infection (CDI): (1) Include 609 rCDI patients undergoing FMT through colonoscopy or enema; (2) 1 week, 1 week after FMT Follow-up for months, 6 months and 1 year.
At each time point, a questionnaire will be conducted on the patients to ask about symptoms (diarrhea, constipation, urgency, cramps), duration, relief, new symptoms, antibiotic use, and Diffuse Shuttle Bacteria detection.
If there is a recurrence, ask the patient about the treatment and the resolution of the symptoms; (3) 447 of them will be followed up for more than 2 years.
Experimental results: (1) During the 1-year follow-up period, more than 60% of patients had diarrhea, less than 33% of patients had constipation, and 9.
5% of patients had recurrence of CDI; (2) Patients with IBD, dialysis-dependent nephropathy, and multiple FMT The risk of diarrhea is higher, and the risk of constipation in female patients is higher, while the risk of constipation in IBD patients is lower; (3) During the long-term follow-up, 188 patients developed 73 new symptoms, of which 13% had gastrointestinal diseases and 10% of their body weight Increase, 11.
8% of new infections.
A number of studies have confirmed that FMT has a good curative effect in the treatment of recurrent CDI and ulcerative colitis, but the curative effect on allergic diseases, inflammatory bowel disease (CD) and autoimmune diseases remains to be confirmed.
CDI is mainly a disease driven by pathogenic microorganisms, which is characterized by the loss of the barrier function of the intestinal microbiota, while FMT can reset and restore the richness and diversity of the intestinal flora to prevent the colonization and pathogenicity of Clostridium difficile Sex.
In a study for the treatment of inflammatory bowel disease (IBD), the combination of corticosteroids and FMT can relieve patients' symptoms for a long time.
In the study of using FMT to treat irritable bowel syndrome (IBS), 2 items showed a significant improvement in the condition, while the other 3 items had no obvious effect.
Of course, this may be related to factors such as the characteristics of patients with IBS, the condition of the donor, the route of administration, and the number of FMTs.
A domestic meta-analysis found that among 26 FMT clinical studies, 3/4, 1/4, and 1/2 of the studies reported that fecal bacteria transplantation has significant effects on liver disease, metabolic syndrome/obesity, and antibiotic resistance.
Clinical efficacy.
In the process of treating complex diseases through FMT, we must understand that the intestinal microbiota is only one of the many factors that cause diseases, and its weight in the pathology and physiology of different diseases is different.
At the same time, the choice of donor for FMT is very important.
For example, there is a study transplanting the fecal flora of a healthy young donor who loves sports, does not smoke, and was born naturally to IBS patients, and the condition has been significantly improved.
Therefore, the abundance of intestinal flora and the existence of health-related species are important factors that need to be considered when selecting a donor.
Studies have shown that transplantation of whole intestinal flora is more accurate than transplantation of colon/colon flora.
Of course, before performing FMT, the condition of the recipient should also be taken into consideration.
Studies have shown that UC patients with improved symptoms after FMT have higher intestinal flora and Candida abundance than before FMT.
In addition, studies have reported that the failure of FMT in the treatment of CD is related to the enrichment of Klebsiella, Actinomycetes and Haemophilus in the intestinal tract of patients.
These studies indicate that the intestinal flora of the recipient at baseline may affect the effect and clinical outcome of FMT.
If microorganisms related to the efficacy of FMT are confirmed, they can help different types of patients choose targeted treatment strategies.
Therefore, long-term monitoring of microorganisms that change before and after FMT treatment is very necessary.
At present, the causal relationship and mechanism between bacterial flora changes and diseases are not clear, and it is difficult to determine the time and dose of FMT.
The response of the same patient to FMT may change over time.
There may also be harmful strains in the donor flora, which may cause infection and infectious diseases.
A domestic study reviewed the development and safety of FMT in the past 20 years and found that serious adverse events occurred in patients with impaired intestinal mucosal barrier.
Therefore, it is still necessary to further clarify the efficacy of FMT and formulate individualized donor-recipient pairing schemes to ensure safe and stable treatment.
In conclusion, in the future FMT research design, it is necessary to formulate precision medical strategies and carry out targeted intervention treatment for each patient.
First of all, suitable FMT donors and recipients should be determined based on clinical, microbiological, immune and metabolic parameters in blood and feces.
At the same time, the intestinal microbiota of the donors and recipients need to be accurately characterized to determine the relationship between disease control and FMT.
Influencing factors related to efficacy.
Secondly, the FMT process is designed according to the characteristics of the recipient, including the characteristics of the donor, treatment methods and auxiliary medical care, to ensure the efficacy of FMT.
After FMT, clinical parameters, immune response and microbial composition should also be specifically monitored.
At present, FMT has been extensively explored in gastrointestinal inflammation, metabolic diseases, cardiovascular diseases, and nervous system.
At the same time, it has also made certain breakthroughs in microbial targeted intervention and auxiliary tumor immunotherapy.
However, the effectiveness of FMT in many studies varies.
This also needs to be more refined and personalized in the future FMT-related research and design for precision medicine.
The application of FMT technology is now on the verge of a new era, and there are still vast unknown areas that we need to explore.
I hope this article will help you in the research of intestinal flora, the application of FMT, and the design of related topics and fund applications.
References 1.
Eusebi LH, Telese A, Marasco G, et al.
Gastric cancer prevention strategies: A global perspective.
J Gastroenterol Hepatol, 2020.
2.
Costello SP, Hughes PA, Waters O, et al.
Effect of Fecal Microbiota Transplantation on 8 -Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.
JAMA, 20193.
Baruch EN, Youngster I, Ben-Betzalel G, et al.
Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.
Science, 2020.
4.
Saha S , Mara K, Pardi DS, et al.
Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.
Gastroenterology, 2021.
END Call for contributions "Medical Formula" is now officially open to fans! The content must be originally published and related to scientific research.
Once adopted, a generous reward (300-2000 yuan) will be given.
Please stamp for details.
"Medical side" has always been committed to serving "medical people", pushing the most cutting-edge and most valuable original clinical and scientific research articles to clinicians and scientific researchers.
The medical department has launched "Laboratory Basics", "SCI Writing Skills", "Document Intensive Reading and Analysis", "Easy Learning of Medical English", "National Natural Science Foundation of China", "Clinical Data Mining", "Gene Data Mining", "R Language Tutorial", "Medical Statistics", "Minimally Invasive Animal Experiment Training" and many other special courses, if you need to know the detailed tweets of the courses, you can follow the "Medical Party" public account and click "Exquisite Topics" to enter the Tencent classroom: https://medfun .
ke.
qq.
com NetEase Cloud Classroom: http://study.
163.
com/u/ykt1467466791112 Customer Service Tel: 15821255568 Customer Service WeChat: yixuefang1234