Alessio Fasano, M.D.

Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children – Harvard Medical School, Boston, MA – U.S.A.

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 the 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.

Increased hygiene and a lack of exposure to various microorganisms have been held responsible for the “epidemic” of chronic inflammatory diseases (CID) that over the past 30-40 years has been recorded in industrialized countries including the U.S. 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, increased hygiene in some developing countries has not led to an increase in CIDas seen in industrialized countries, casting some doubts on the validity of the hygiene hypothesis.

This observation has 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 hypotheses have been formulated.  There is growing evidence that many CIDs are characterized by a change in microbiome composition. While factors such as modality of delivery, neonatal feeding regimens, use of antibiotics, and infections can influence microbiota composition, diet is by far the most important variable affecting the 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. This approach has already been clinically implemented for the treatment of inflammatory bowel diseases.