How Nutrition Can Impact Gut Microbiome Composition, Intestinal Permeability and Antigen Trafficking Leading To Chronic Inflammatory Diseases
Alessio Fasano, MD, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children; Harvard Medical School, Boston, MA, USA; European Biomedical Research Institute Salerno (EBRIS) Salerno, Italy.

Improved hygiene leading to a reduced exposure to microorganisms have been implicated as one possible cause for the ‘epidemic’ of immune-mediated diseases, particularly non-infective chronic inflammatory diseases (CID), in industrialized countries during the past 3-4 decades now affecting millions of individuals. The social and financial burdens imposed by these chronic, debilitating diseases include poor quality of life, high health care costs, and substantial loss of productivity. That is the essence of the hygiene hypothesis that argues that rising incidence of these pathologies may be, at least in part, the result of lifestyle and environmental changes that have made us too "clean" for our own good. Interestingly, increase hygiene in some developing countries did not lead to an increase in CID as seen in industrializing countries, casting some doubts on the validity of the hygiene hypothesis.

Apart from genetic makeup and exposure to environmental triggers, three more elements have been recently identified being key players in the pathogenesis of CID. A third element is the inappropriate Increase in intestinal permeability, which may be influenced by the composition of the gut microbiota, has been proposed in the pathogenesis of these diseases. Intestinal permeability, together with antigen (Ag) sampling by enterocytes and luminal dendritic cells, regulates molecular trafficking between the intestinal lumen and the submucosa, leading to either tolerance or immunity to non-self Ag. This tolerance-immune response balance is influenced by the function of the immune system (both innate and adaptive immune response) as a forth element involved in the pathogenesis of CID. Finally, the composition of gut microbiome and its epigenetic influence on the host genomic expression has been identified as a fifth element in causing CID. The gut microbiome consists of more than 100 trillion microorganisms, most of which are bacteria. It has been just recently recognized that there is a close bidirectional interaction between gut microbiome and our immune system and this cross talk, particularly during infancy, is highly influential in shaping the host gut immune system function and, ultimately, the tolerance/immune response balance.
This observation led to a revisitation of the possible causes of CID epidemics. With the appreciation that the gut microbiome plays a decisive role in either generating (mucosal) tolerance or leading the way to the development of inflammatory conditions, alternative hypothesis have been formulated. There is growing evidence that many CID are characterized by a change in microbiome composition. While factors such as modality of deliver, neonatal feeding regimens, use of antibiotics, infections can influence microbiota composition, diet is by far the most important variable affecting gut ecosystem. Therefore, re-shaping gut microbiota through dietary manipulation is becoming an extremely active area of research for the prevention or treatment of a multitude of CID. Celiac disease and autism spectrum disorders will be discussed as clinical examples of this new paradigm.