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Higher levels of microbiota engraftment linked to greater chances of transplantation success



From incurable intestinal infections to metabolic syndrome, from melanoma, to chronic inflammatory bowel disease, such as irritable bowel syndrome, to Tourette’s syndrome: many diseases can potentially be cured by Fecal Microbiota Transplantation (FMT), and researchers from the Catholic University, Rome and the University of Trento have shown that the greater the level of engraftment of the transplanted microorganisms, the greater the chances of success of the therapy.

This is the core of the study published in the journal Nature Medicine coordinated by Gianluca Ianiro, Researcher in diseases of the Digestive System at the Catholic University and consultant of the UOC of Gastroenterology at the Agostino Gemelli University Polyclinic Foundation” IRCCS and by Professor Nicola Segata, Professor of Genetics at the University of Trento and in the Cibio Department of the University of Trento and the European Institute of Oncology in Milan, Italy.

Microbiota transplantation is a new therapeutic frontier that embraces different fields of medicine, not only gastroenterology, but even, for example, oncology, (it has been seen that the efficacy of some cancer therapies is influenced by the microbiota). It’ clearer and clearer that the gut microbiota -the set of microorganisms that live in symbiosis in our gut performing so many functions in addition to the digestive one- is important for human health and has a crucial role both for the digestive tract, the immune system, and even (through the gut-brain connection operated by the vagus nerve) for the nervous system, with possible repercussions on complex diseases such as multiple sclerosis and autism.”

Antonio Gasbarrini, full professor of Internal Medicine at the Catholic University and director of the Department of Medical and Surgical Sciences and of the Internal Medicine and Gastroenterology Operating Units and CEMAD-Digestive Disease Center of the Agostino Gemelli IRCCS University Polyclinic Foundation

Transplantation is done by isolating and purifying donor microbiota collected from feces and transferring it by various ways (in capsules or during a colonoscopy) to the donor patient. What is not really clear of this therapeutic procedure is how well the transplanted microorganisms engraft in the recipient patient’s intestine.

Experts have analyzed with sophisticated genomic sequencing and computer analysis techniques a total of more than 1,300 gut microbiota samples (collected from feces) from donors and recipient patients with as many as eight different diseases (C. difficile, infections with intestinal multiresistant bacteria, metabolic syndrome, melanoma, chronic inflammatory bowel disease, irritable bowel syndrome, chemotherapy diarrhea, Tourette’s syndrome).

“Thanks to the ability of the analysis based on genomic sequencing techniques,” Segata explains, “to identify the different bacterial strains present in the microbiota, which have a specific pattern for each person, we were able to understand whether a particular strain was transmitted from the donor to the recipient”.

“We have seen,” Ianiro explains, “that patients with higher levels of microbiota engraftment achieved a better clinical response; also that engraftment is greater in patients with infectious diseases (who have a less severe microbiota imbalance -dysbiosis) than in those with chronic diseases (who have more complex and radicate dysbiosis).”

“We also found,” Ianiro adds, “that patients treated with antibiotic therapy prior to the transplant procedure had higher engraftment, and that infusion of the microbiota via multiple routes of administration (e.g., capsules along with colonoscopy) promoted engraftment. It was also found that some microbial species (particularly Proteobacteria and Actinobacteria) engraft better than others (e.g., the phylum Firmicutes).

Finally, “we have shown that by using artificial intelligence we can predict with relevant accuracy the composition of the donor microbiota after transplantation, and this could then lead to identifying the best donors whose feces are more successful in increasing the diversity of the microbiota (which is a parameter of microbiota health) post-fecal transplantation,” Ianiro and Segata point out.

“This study is the result of a fruitful collaboration and years of study by our research group on gut microbiota transplantation. It is thanks to these advances in knowledge about the conditions that maximize the success of transplantation,” Giovanni Cammarota, Associate Professor in Gastroenterology at the Catholic University and Director of the UOC of Gastroenterology at the Agostino Gemelli IRCCS University Polyclinic Foundation explains, “that we will increasingly be able to exploit the procedure in clinical practice for the treatment of many diseases.

“This is why,” Ianiro concludes, ” we have recently won a grant to pursue, with the Trento and Milan group and our Medical Oncology unit, a randomized, controlled trial aimed at evaluating whether fecal transplantation succeeds in improving the therapeutic response to immunotherapies (the latest frontier of oncology drugs) in patients with advanced kidney cancer. Already for other cancers, such as melanoma, there is initial and promising evidence about the connection between microbiota and immunotherapy success, Professor Cammarota concludes.

Source:

Journal reference:

Ianiro, G., et al. (2022) Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases. Nature Medicine. doi.org/10.1038/s41591-022-01964-3.



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