Preface

Before the completion of the human genome project, the paradigm of human diseases was based on the assumption that being born with genes associated to any disease was a signed destiny to develop it.   With the discovery that we are made by only 23,000 genes, we now appreciate that the environment plays a major role in determine if and when we develop chronic inflammatory diseases.  Indeed, over the past few decades we have witnessed a dramatic rise of chronic inflammatory diseases affecting humankind with different type of outcomes depending on the socio-economic environment in which children are born and raised.  Children living in impoverished areas around the world often develop stunted growth from 4 to 24 months of age, a concern that is heightened by potential lasting consequences of impaired cognitive development throughout their lifespan. While in the past it was believed that malnutrition was the driving factor leading to these clinical outcomes, we now know that chronic, subclinical inflammation most likely is the key element leading to poor physical and intellectual growth. Similarly, chronic inflammatory processes starting in childhood seem to be responsible of chronic inflammatory diseases “epidemics”, including allergic, autoimmune, metabolic, neurodegenerative, and tumoral diseases, detected in industrialized countries during the past few decades that can develop at any age. The combination of pre-, peri-, and post-natal factors may influence if and when the immune system unleash inflammation.  Under ideal conditions, including healthy pregnancy, normal delivery, appropriate feeding (breast-feeding, natural food), limited use of antibiotics, and few infections during the first 1000 days, the human microbiome stays in balance and train the immune system to generate inflammation only when there are the extreme conditions to be protected against “enemies”, so maintaining normal health and prevent aberrant pro-inflammatory or allergic responses. Conversely, increase C-section practice even when not medically indicated, decrease breast-feeding practice, excessive use of antibiotics, all cause an imbalanced microbiome (dysbiosis), so training the immune system to continuously unleash inflammation also when not needed, leading to chronic inflammatory diseases in genetically predisposed individuals.  While research around the role of the microbiome is growing exponentially, clinical applicability is lacking. Current studies evaluate the microbiota at different taxonomic levels, at different time points, from different sites, by different platforms, and with different computational strategies. This is due to rapid growth in the field, challenged by narrow focus of individual studies, small sample sizes, cross-sectional design, and lack of standardization. The focus has also mainly been on the bacterial microbiota, while viruses, parasites, and fungi are also likely to be important members of this large co-evolving ecosystem that lives on and within us.  Further mechanistic studies to understand these human-microbe interactions will be important. We are much more likely to discover clinically meaningful and successful interventions if they are designed based on established mechanistic understanding. Therefore, we need to transition from descriptive to mechanistic studies of the microbiome, for promising translational medicine to be possible. In order to implement this transition, we need to appreciate that studies on human genetics, microbiome, immune functions, and environmental factors need to be highly integrated following the overall theme that human phenotypes are mainly dictated by the activation of specific metabolic pathways that may change key functions influencing the balance between health and disease. Specifically, it appears now clear that the human microbiome may epigenetically influence the expression of a variety of genes controlling key metabolic functions that control the shift from genetic predisposition to clinical outcome.  Therefore, this book provides the state-of-the-art of current knowledge on the human metabolome and how the use of novel technologies coupled with robust metadata and artificial intelligence analysis may lead to a radical paradigm shift of the future of human health by allowing personalized interventions (precision medicine) and, even more impactful and exciting, the possibility of disease interception and primary prevention. If properly implemented, these studies have the potential to dramatically impact our understanding of and approach to a variety of complex chronic inflammatory diseases. Only then will breakthrough treatment and prevention strategies likely emerge. 

Mucosal Immunology and Biology Research Center and Center for Celiac Research, Harvard Medical School, Massachusetts Gen Hosp Children, Mucosal Immunology and Biology Research Center, Boston, MA 02114, United States

Prof. Alessio Fasano is an Italian-born medical doctor, pediatric gastroenterologist and researcher. He currently holds many roles, including professor of pediatrics at Harvard Medical School and professor of nutrition at Harvard T.H. Chan School of Public Health, both in Boston. He serves as director of the Center for Celiac Research and Treatment at MassGeneral Hospital for Children (MGHfC) and co-director of the Harvard Medical School Celiac Research Program. In addition, he is director of the Mucosal Immunology and Biology Research Center at MGHfC, where he oversees a research program with approximately 50 scientists and staff researching a variety of acute and chronic inflammatory diseases, including cystic fibrosis, celiac disease, enteric infections and necrotizing enterocolitis. A common theme of these programs is the study of the emerging role of the gut microbiome in health and disease. Fasano is also the scientific director of the European Biomedical Research Institute of Salerno (EBRIS) in Italy. Along with these leadership positions, he is a practicing outpatient clinician in pediatric gastroenterology and nutrition and the division chief.

Fasano is considered an expert and pioneering researcher worldwide in the field of celiac disease and bacterial pathogenesis. Not only did he found the premier celiac research center in the United States, but the impact of his more than 300 peer-reviewed journal publications and 160 patents has greatly shaped and advanced the knowledge of a multitude of chronic inflammatory diseases and immune diseases. He was among the top 1 percent cited scientists worldwide based on Web of Science Group’s annual list of Highly Cited Researchers.
Throughout his career, he has prioritized and advocated for his patients by disseminating his research to the general public along with expansive outreach efforts. He often collaborates with celiac support organizations and government agencies to work toward this goal, and actively participates in fundraising efforts for the Center for Celiac Research and Treatment. He is the author of multiple books and has been featured in journals, magazines and interviews for the general public.
He has published numerous groundbreaking research studies, including the 2000 discovery of the zonulin protein and its regulation and modulation of intestinal permeability. In 2003, he published the results of the epidemiological study that demonstrated the prevalence of celiac disease in the U.S. to be far higher than previously thought, at a rate of 1 in 133 persons. His work also contributed to the development of an anti-tissue transglutaminase (tTG) diagnostic test for celiac disease, that is part of standard diagnostic testing for celiac disease.