From incurable intestinal infections to metabolic syndrome, from melanoma to irritated intestinal syndromes, or Tourette: many diseases are estimated to be potentially treatable through the transplantation of fecal microbiotics.
In August and September 2022, three independent scientific groups published research results that describe the dynamics of microbiomus after transplantation or, in simple terms, assess the success of such therapy.
How's the kala transplant working?
FFM is the transfer to the recipient of samples of fluid and bacteria collected at the bottom of the donor's intestine, usually using this procedure to remediate the damaged microflora in the patient's intestine and treat the diseases associated with it.
Although the first records of the use of donor feces as a cure for food poisoning and diarrhoea were recorded in the Chinese Handbook of Emergency Medicine as early as the fourth century, the method became popular in evidentiary medicine relatively recently.
The first study on the use of fecal microbiom transplant was published in 1958 by Ben Ezeman and other surgeons from Colorado, who noted that the use of fecal enema had helped to cure four critical patients with a fluminant pseudoembranous colit; this is a severe intestinal disease that causes inflammation and mucous education.
Later, it was shown that the disease causes the clostridium difcile bacteria and that TFM is one of the best ways to treat it. According to a large number of studies, the effectiveness of the TFM is 90 per cent when treating pseudo-emerocrine entrocolitis.
Modern research has shown that the sum of all microorganisms in humans, microbes, is important for human health; changes in their composition affect microbial interactions with human organisms; therefore, human intestinal microbial ecosystem disorders are associated with many metabolic, inflammatory and infectious diseases.
The recipient is more important than the donor
Although clinical trials have shown that TFMs can effectively treat certain intestinal disorders, the mechanism for their action remains unclear. Some suggest that donor intestinal microbiomes have useful properties that help bring the recipient's intestine back to health, but this has never been systematically studied.
In a paper published in Nature Medicine, researchers from the European Molecular Biology Laboratory used data from more than 300 transplants of human fecal microbiotics to gain insight into what happens when two intestinal microbiomas run into each other.
Using clinical and metagenomic data, researchers found that the recipient, not the donor, primarily determined the microbial composition resulting from the procedure.
Using machine learning, scientists analysed the factors that determine the microbial dynamics after transplant, including the presence or absence of individual microbial species, which show that the wealth of species, as well as the extent to which the microbial intestine of the recipient's intestine differs from the donor, are the main factors that determine which species will survive and thrive after transplantation.
This means that there is no one-size-fits-all donor, researchers believe, but personal treatment is available for everyone.
Kill first, cure later!
Researchers from Hohenheim University in Germany came to a similar conclusion, and in a paper published in Cell Reports Medicine, they showed that only one of the two strains of the same bacteria that existed before the transplant survived.
In the study, scientists used a special method to detect even minor changes in microbiom. In addition to their own analyses, they also recorded data from 14 other clinical studies and evaluated data from more than 250 individuals who had received a kala transplant. Particular attention was paid to the transmission of individual bacteria or strains during transplantation.
Their most important conclusion is that, regardless of the main disease, after transplantation, most types of bacteria were dominated by only one strain. The patients mostly contained either the same strain as before the treatment, or a new strain, but only rarely a mixture. The more the existing intestinal microbe was damaged before the transplant or the pre-treatment of antibiotics, the more successful donor microbes could be.
Researchers say that these results explain the different effectivenesss in the treatment of transplants of individual diseases, for example, in the case of recurrent infections caused by the clostridoides difficile bacteria, the efficiency is 90 per cent, due to the long-term use of antibiotics, which almost completely destroy the recipient ' s own microbe.
On the other hand, the low efficiency of transplants in treating inflammable intestines with ulcer, obesity or diabetes is due to the high level of protection of their own bacteria, which hinder transplantation.
The conclusion is simple, as scientists point out, pre-treatment with antibiotics and intestinal wash before transplantation increases the likelihood that the digestive tract will be colonized by donor bacteria and the effectiveness of treatment.
A study published in Nature Medicine, by researchers from the Catholic University in Rome and the University of Trento, which analysed over 1,300 samples of intestinal microbiotics from donors and patients with eight different diseases, including bacterial disorders, melanoma, intestinal syndrome and Tourette syndrome, using sophisticated methods of genomic sequencing and computer analysis.
Researchers also found that patients who received antibiotics prior to transplantation had a higher degree of exposure, and the introduction of microbiotics had improved the effectiveness of treatment in several ways.
Scientists have shown that artificial intelligence is very accurate in predicting the composition of donor microbiotics after transplantation, and this can then lead to the identification of the best donors whose feces will be more successful in individual transplants.
Some researchers believe that kala transplantation can be a universal drug that can help almost any problem; for example, there are many studies that indicate that people with mental illness have another microbe, and the assumption that TFMs can alleviate some of the symptoms associated with them.
But most of the findings in this area are based on experiments conducted on model organisms, usually in laboratory mice. Although laboratory mice are quite clever, many of the "mice models of mental illness" are contradictory. Some researchers question the fact that mice may have depression or borderline personality disorder in the same way as humans. Therefore, it is too early to talk about a universal solution.
Nevertheless, great progress in the study of FPMs and further research may show that the range of possible applications of such therapy is much wider than is currently available.