Monday, 19 September 2022

New insights on microbiota transplantation

Nature Medicine published the results of a study conducted at Cattolica University and the University of Trento

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Faecal Microbiota Transplantation (FMT) can be beneficial for a wide range of diseases, including intestinal infections that cannot be treated with antibiotics, metabolic syndrome, melanoma, chronic inflammatory bowel disease, irritable bowel syndrome, Tourette's syndrome, and others. Researchers from Cattolica University, Rome campus, and the University of Trento have demonstrated that the higher the level of engraftment of the transplanted microorganisms, the greater the chances of success of the treatment.

This is the essence of the study published in Nature Medicine and coordinated by Gianluca Ianiro, researcher in diseases of the digestive system at Cattolica University and staff physicians of the Operative Unit of Gastroenterology at Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, and Nicola Segata, professor of genetics at the University of Trento, Cibio Department of the University of Trento and the European Institute of Oncology in Milan. 

"Microbiota transplantation– explains Antonio Gasbarrini, professor of Internal Medicine at Cattolica University and director of the Department of Medical and Surgical Sciences and of the Operative Units of Internal Medicine and Gastroenterology and the Center for Digestive Diseases - Cemad of Fondazione Policlinico Universitario 'A. Gemelli' IRCCS - is a new therapeutic frontier that embraces different sectors of medicine, not only gastroenterology, but even, for example, oncology (it has been seen that the microbiota has an impact on the effectiveness of certain cancer treatments). In particular, it is now widely accepted that the gut microbiota – the set of microorganisms that live in symbiosis in our intestine carrying out many functions besides the digestive one – is important for human health, and plays an important role for the digestive tract and for the immune system, and even (through the gut-brain connection operated by the vagus nerve) for the nervous system, with possible impacts on complex diseases such as multiple sclerosis and autism".

The transplant is carried out by isolating and purifying the donor microbiota collected from the faeces and transferring it in various ways (in capsules or during a colonoscopy) to the recipient. What remains unclear in this procedure is precisely the level of engraftment of the transplanted microorganisms in the recipient's intestine.

Using highly sophisticated genomic sequencing and computer analysis techniques, the researchers have analyzed more than 1300 samples of intestinal microbiota (collected from faeces) from donors and recipients with eight different diseases (C. difficile, infections from multidrug-resistant intestinal bacteria, metabolic syndrome, melanoma, chronic inflammatory bowel disease, irritable bowel syndrome, chemotherapy-induced diarrhoea, Tourette's syndrome).

"Thanks to new analysis techniques that we have developed and that are based on metagenomic sequencing techniques – explains Segata – we have been able to identify the different bacterial strains in the microbiota, which are very specific for each person, and understand if a particular strain has been transmitted from the donor to the recipient".

"We have seen – explains Ianiro - that patients with a higher level of microbiota engraftment have obtained a better clinical response and that the engraftment is greater in patients with infectious diseases (who have a simpler microbiota imbalance, dysbiosis, that is more easily restored) than those with chronic diseases (who have more complex and long established dysbiosis)".

"We also found – continues Ianiro – that patients treated with antibiotic therapy prior to the transplant procedure had a greater engraftment and that the infusion of the microbiota through multiple routes of administration (e.g. capsules and colonoscopy) favours engraftment". "It has also emerged – Segata added – that some microbial species (in particular those belonging to the phyla of Proteobacteria and Actinomycetes) engraft more easily than others".

Finally, "we have shown that with artificial intelligence we can predict with significant accuracy the composition of the donor's microbiota after the transplantation, and this could therefore lead to identifying donors whose faeces are able to further increase the diversity of the microbiota (which is a health parameter of the microbiota) after faecal transplantation" underlined Ianiro and Segata.

"This study is the result of a fruitful collaboration and years of study by our research group on gut microbiota transplantation. It is precisely thanks to these advances on the conditions that maximize the success of the transplant – explains Giovanni Cammarota, associate professor of gastroenterology at the Cattolica University and director of the Operative Unit of Gastroenterology at Fondazione Policlinico Universitario 'A. Gemelli' IRCCS - that we will increasingly succeed in using this procedure in clinical practice to treat many diseases".

"It is no coincidence – concludes Ianiro – that we have recently been awarded funding to continue, with the Trento and Milan groups and with our Medical Oncology unit, a randomized and controlled study to establish whether faecal transplantation can improve the therapeutic response to immunotherapies (the last frontier of oncological drugs) in patients with advanced kidney cancer". "For other types of cancers, such as melanoma, there is initial and promising evidence about the connection between microbiota and the success of immunotherapy," concludes Cammarota.