From incurable intestinal infections to metabolic syndrome, from melanoma to irritable
But is the new therapy really capable ofget rid of all diseases and universally works well for everyone? In August and September 2022, three independent scientific groups at once published the results of studies that describe the dynamics of the microbiome after transplantation or, in simple terms, assess what the success of such therapy depends on.
How does a stool transplant work?
FMT is the transfer to the recipient of fluid samples andbacteria collected in the lower intestine from a donor. As a rule, such a procedure is used to restore the disturbed intestinal microflora of the patient and treat diseases associated with it.
Although the first records of the use of donorfeces as a remedy for food poisoning and diarrhea was registered in the "Handbook of Emergency Medicine" by the Chinese Hong Ge back in the 4th century, in evidence-based medicine this method has become popular relatively recently.
First study on the use of transplantThe Fecal Microbiome was published in 1958 by Ben Eiseman and other Colorado surgeons. They noted that the use of fecal enemas helped cure four critically ill people with fulminant pseudomembranous colitis. This is a serious disease of the large intestine, which causes inflammation and formations on the mucous membrane.
It was later shown that this disease causesthe bacterium Clostridium difficile and that FMT is one of the best ways to treat it. According to a large number of studies, in the treatment of pseudomembranous enterocolitis, the effectiveness of FMT reaches 90%.
Modern research has shown thatThe totality of all microorganisms in the human body, the microbiome, is essential to human health. Changes in its composition affect microbial interaction with the human body. Therefore, disturbances in the human gut microbial ecosystem are associated with many metabolic, inflammatory, and infectious diseases.
The recipient is more important than the donor
Although clinical trials have shown that FMTmay effectively treat certain bowel disorders, their mechanism of action remains unclear. Some suggest that the gut microbiomes of donors have beneficial properties that help return the recipient's gut to a healthy state. However, this has never been systematically studied.
In a paper published in the journal NatureMedicine, researchers at the European Molecular Biology Laboratory used data from more than 300 human fecal microbiota transplants to gain insight into what happens when two gut microbiomes collide.
Using clinical and metagenomic data, the researchers found that the recipient, rather than the donor, primarily determines the microbial composition resulting from this procedure.
Using machine learning, scientistsanalyzed the factors that determine microbial dynamics after transplantation, including the presence or absence of individual microbial species. Their results suggest that species richness (a measure of how diverse the recipient's gut microbiome is prior to transplantation), as well as how different the recipient's gut microbiome is from that of the donor, are major factors in determining which species will survive and thrive after transplantation.
This means that there is no universal donor, the researchers believe, but it is possible to choose a personalized treatment for everyone.
Kill first, heal later!
Researchers fromUniversity of Hohenheim in Germany. In a paper published in the journal Cell Reports Medicine, they showed that out of two strains of the same bacterium that existed before the transplant, only one survived.
During the study, scientists useda special method to be able to detect even small changes in the microbiome. In addition to their own results, they also recorded data from 14 other clinical studies and evaluated data from more than 250 people who received stool transplants. Particular attention has been paid to the transmission of individual bacteria or strains during transplantation.
Their most important takeaway:regardless of the underlying disease, after transplantation, only one strain prevailed for most types of bacteria. Patients mostly contained either the same strain as before treatment, or a new, transferred strain, but only in rare cases a mixture. The more the existing gut microbiome was damaged prior to transplantation or disrupted by antibiotic pretreatment, the more successfully the donor microbes could colonize.
The researchers say these resultsexplain the different effectiveness in the treatment of transplantation of individual diseases. For example, in the case of recurrent infections caused by the bacterium Clostridioides difficile, the efficiency reaches 90%, which is associated with long-term use of antibiotics, which almost completely destroy the recipient's own microbiome.
On the other hand, the low efficiency of transplantationin the treatment of patients with inflammatory bowel disease, ulcerative colitis, severe obesity or diabetes, due to the high degree of preservation of their own bacteria, which interfere with transplantation.
The conclusion is simple, scientists note, preliminaryantibiotic treatment and bowel lavage before transplantation increase the likelihood of colonization of the digestive tract by donor bacteria and the effectiveness of treatment.
Factors affecting the survival rate of donor feces. Image: Daniel Podlesny et al., Cell Reports Medicine
Find the right personalized treatmentAI will help, which was developed by scientists from the Catholic University of Rome and the University of Trento. In a study published in the journal Nature Medicine, experts analyzed a total of more than 1,300 gut microbiota samples (collected from faeces) from donors and recipient patients with eight different diseases, including bacterial disorders, using sophisticated genome sequencing and computer analysis techniques. , melanoma, irritable bowel syndrome and Tourette's syndrome.
The researchers also found that patientsthose who received antibiotic therapy before the transplantation procedure had a higher engraftment. In addition, the administration of the microbiota in several ways (eg, capsules along with colonoscopy) increased the effectiveness of the treatment.
Scientists have shown that with the help of artificialintelligence, it is possible to predict with high accuracy the composition of the donor microbiota after transplantation, and this can then lead to the identification of better donors whose faeces will be more successful in an individual transplant.
Some researchers believe thatstool transplantation can act as a universal cure for almost any problem. For example, there are many studies reporting that people with mental illness have a different microbiome and suggest that FMT may alleviate some of the symptoms associated with them.
But most of the findings in this area are based onexperiments performed on model organisms, usually laboratory mice. While lab mice are pretty smart, many of the "mouse models of mental illness" are inconsistent. Some researchers question the fact that a mouse can have depression or borderline personality disorder in the same way that a human can. Therefore, it is too early to talk about a universal solution.
Nevertheless, great progress in the study of FMT and further research may show that the range of possible applications of such therapy is much wider than it seems today.
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