Microbiome, from doctors (for doctors) comes the toolbox on frontiers of care

A series of valuable diagnostic-therapeutic applications based on the microbiome could really be just around the corner. And now the toolbox set up by doctors for doctors themselves arrives in an article published in the scientific journal Cell, thanks to a team of experts from Gemelli and the Catholic University. A reasoned point on results with extraordinary potential, also useful in bridging that communication gap between basic researchers and clinicians that is slowing down their implementation.

'We thought,' explains Dr Gianluca Ianiro, researcher in Gastroenterology at the Catholic University and medical director UOC of Gastroenterology Policlinico Gemelli IRCCS, 'that the time had come to take stock of the possible clinical applications of the microbiome. Despite an enormous amount of research and studies on the microbiome, clinical applications are still very scarce, sometimes unorthodox, sometimes 'primordial'. But this will soon change, because the microbiome is the perfect target for precision medicine, specific from person to person and variable in composition depending on life events and diet'. So why is it not yet applied in clinical practice? 'For a series of challenges, of 'brakes',' explains Dr Serena Porcari, UOC of Gastroenterology Fondazione Policlinico Gemelli IRCCS and first author of the work on Cell-. The first is biological: identifying causal links between microbiome composition and pathologies is difficult due to the heterogeneity and complexity of the intestinal microbiome. The second is methodological: clinical studies on the microbiome are complex because they have to take into account diet, drugs taken, and environmental influences in their design; there is also a lack of standardised protocols for its analysis. The third is logistical: there is a lack of large multicentre studies because most of the evidence in this field comes from academic research conducted by single centres and with low sample sizes (funding is also scarce). There is little communication between clinicians and basic scientists. The last 'brake' is cultural: the limited familiarity with the microbiome of most physicians prevents the clinical application of research data'.

Da sinistra Antonio Gasbarrini, Serena Porcari, Gianluca Ianiro e Giovanni Cammarota

But the results obtained so far do, however, portend prospects for both diagnostic and therapeutic use of the microbiota within the next five to ten years (especially on the diagnostic front). 'In the first case,' explains Professor Antonio Gasbarrini, Dean of the Faculty of Medicine and Surgery and Professor of Internal Medicine at the Università Cattolica del Sacro Cuore, Director of the UOC Internal Medicine and Gastroenterology and of the Centre for Diseases of the Digestive System (Cemad) at the Fondazione Policlinico Universitario Gemelli IRCCS, 'the microbiota could be used as a biomarker of early disease; in this field, the most convincing studies so far are those on colon cancer. Or it could be used as a predictor of response to a therapy (e.g. immunotherapy in oncology), or the microbiota could be used for the differential diagnosis between ulcerative colitis and Crohn's disease. On the therapeutic side, we have several directions. That of faecal transplantation is becoming more and more refined and is moving towards microbial consortia (a sort of cocktail of selected microbes, already used for the treatment of Constridium difficile colitis); another promising prospect is that of bacteriophages, viruses that colonise pathogenic bacteria and destroy them (the 'lytic' phages); finally, there is that of engineering probiotics (producers or carriers of beneficial compounds)'.

So how can the use of the microbiome in clinical practice be accelerated? 'Through several possible actions,' argues Professor Giovanni Cammarota, Professor of Gastroenterology at the Catholic University and director of the UOC of Gastroenterology Policlinico Universitario A. Gemelli IRCC-: standardise research and reporting of microbiota testing from one laboratory to another; improve the design of clinical trials; refine the rationale of trials (understand the mechanisms through basic research and build clinical trials on the results of this research); connect the world of research with that of clinicians, do training and promote interdisciplinarity'. What's around the corner? 'The first thing coming to the clinic,' Dr Ianiro reveals, 'will be a colon cancer screening test that can guide towards the indication for colonoscopy for people who, in addition to a positive faecal occult blood test (FIT, Fecal Immunochemical Test), present a particular type of microbiota. Another test around the corner is the one to predict the response to immunotherapy in a cancer patient (the most solid data acquired so far are on lung cancer and melanoma). On the therapy front, in addition to the well-established indications of microbiota transplantation for Costridium 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 do damage (e.g. in patients awaiting organ transplantation). The next frontier will be to use the microbiota to enhance the action of immunotherapy in cancer'.