ABSTRACT
Improved hygiene leading to a reduced exposure to microorganisms has been implicated as one possible cause for the “epidemic” of immune-mediated diseases, particularly noninfective chronic inflammatory diseases (CID), in industrialized countries during the past three to four 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, increased hygiene in some developing countries has not led 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 as 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, which 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 responses) as a fourth element involved in the pathogenesis of CID. Finally, the composition of the 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 and the growing evidence that many CIDs are characterized by gut dysbiosis have redirected the scientific interest on the epigenetic role of gut microbiome in causing the CID epidemics. Given its unique “fingerprint” even among individuals affected by the same CID, reshaping microbiome composition and function would represent a potential intervention for personalized diagnosis, treatment, and even primary prevention for a variety of CIDs.
