The article summarizes results of research and possible future clinical applications of the microbiome and provides instructions for doctors. More communication is needed between basic and clinical research to accelerate the arrival of this valuable tool at the patient's bedside. There are many possible diagnostic and therapeutic applications: from the fight against antibiotic resistance to colon cancer screening, predicting response to immunotherapy and enhancing its effectiveness in the fight against cancer.
Both diagnostic and therapeutic use of the microbiota will become reality within the next 5-10 years. It emerges from an "informative" article published in Cell, written by doctors for doctors, to inform clinicians that a series of valuable diagnostic and therapeutic applications based on the microbiome could be just around the corner and bridge the communication gap between basic researchers and clinicians, which is slowing down their implementation.
Dr Gianluca Ianiro, researcher in Gastroenterology at the Catholic University and medical director of the Gastroenterology Unit at the Gemelli IRCCS Polyclinic explains: 'We thought that the time had come to take stock of the possible clinical applications of the microbiome. Despite a huge amount of research and studies on the microbiome, clinical applications are still very scarce, sometimes not entirely orthodox, sometimes "primitive". But this will soon change, because the microbiome is the perfect target for precision medicine, specific to each individual and variable in composition depending on life events and diet."
So why is it not yet being applied in clinical practice? "Because of a series of challenges, of 'brakes", Dr Serena Porcari, UOC of Gastroenterology at the Fondazione Policlinico Gemelli IRCCS and first author of the paper in Cell explains. The first is biological: it is difficult to identify causal links between the composition of the microbiome and diseases due to the heterogeneity and complexity of the intestinal microbiome. The second is methodological: clinical studies on the microbiome are complex because they must take into account diet, medications taken, and environmental influences in their design; there is also a lack of standardized protocols for its analysis. The third is logistical: there is a lack of large-scale multicenter studies because most of the evidence in this field comes from academic research conducted by individual centers with small sample sizes (funding is also scarce). There is little communication between clinicians and basic scientists. The final "obstacle" is cultural: most doctors' limited familiarity with the microbiome prevents the clinical application of research data.
However, the results obtained so far suggest prospects for both diagnostic and therapeutic use of the microbiota within the next 5-10 years (especially on the diagnostic front).
Professor Antonio Gasbarrini, Dean of the Faculty of Medicine and Surgery and Professor of Internal Medicine at the Catholic University of the Sacred Heart, Director of the Internal Medicine and Gastroenterology Unit and the Centre for Digestive Diseases (CEMAD) at the Gemelli IRCCS University Polyclinic Foundation explains: "In the first case the microbiota could be used as a biomarker for early disease; in this area, the most convincing studies to date are those on colon cancer. Or it could be used as a predictor of response to therapy (e.g., immunotherapy in oncology), or the microbiota could be used for differential diagnosis between ulcerative colitis and Crohn's disease.
On the therapeutic side, we have several directions. One is faecal transplantation, which is becoming increasingly refined and is moving towards microbial consortia (a sort of cocktail of selected microbes, already used for the treatment of Clostridium difficile colitis). Aanother promising prospect is that of bacteriophages, viruses that colonize pathogenic bacteria and destroy them ("lytic" phages); and finally, there is the engineering of probiotics (producers or carriers of beneficial compounds).
Professor Giovanni Cammarota, Professor of Gastroenterology at the Catholic University and Director of the UOC of Gastroenterology at the A. Gemelli IRCC says: "we accelerate the use of the microbiome in clinical practice through various possible actions". By standardising research and reporting of microbiota tests from one laboratory to another; improving the design of clinical trials; refining the rationale for trials (understanding the mechanisms through basic research and building clinical trials on the results of this research); connecting the world of research with that of clinicians, providing training and promoting interdisciplinarity.
'The first thing to arrive in clinics, will be a colon cancer screening test that can guide the indication for colonoscopy for people who, in addition to a positive faecal occult blood test (FIT, Fecal Immunochemical Test), have a particular type of microbiota." Dr Ianiro reveals. Another test on the horizon is one to predict the response to immunotherapy in cancer patients (the most solid data acquired so far are on lung cancer and melanoma). On the therapeutic front, in addition to the established indications for microbiota transplantation for Clostridium difficile colitis, the next applications will be on the eradication of multi-drug resistant (MDR) bacteria such as Klebsiella in intestinal infections or before they cause damage (e.g. in patients awaiting organ transplantation). The next frontier will be to use microbiota to enhance the action of immunotherapy in oncology.
