Research over the past decade has accumulated a large body of evidence linking alterations in the gut microbial
composition to several diseases, such as inflammatory bowel disease, asthma, arthritis, obesity and cardiovascular
disease. Furthermore, it is now clear that the normal intestinal microbiota also influences numerous physiological
aspects in the healthy host, including organ morphogenesis, immune system and gastrointestinal tract
development and maturation, intestinal vascularization, tissue regeneration, carcinogenesis, bone homeostasis,
metabolism and behaviour. An important insight that has come from these studies it that the timing of colonization of germ-free mice seems to be crucial if these mice are to recapitulate the phenotypes of conventionally raised mice. Whereas colonization of adult germ-free mice restores adiposity to normal levels113, colonization before weaning is required to normalize behaviour and protect against the iNKT cell accumulation that is associated with asthma and inflammatory bowel disease41,131. Such early microbial colonization might have an epigenetic effect on the host through
early-life imprinting, but it remains to be demonstrated how the gut microbiota achieves this. It is possible that
in Tlr2‑deficient mice, the altered microbiota contributes to altered DNA methylation patterns in cells of the colonic mucosa135. The impact of the gut microbiota as a modulator of methylation in other organs remains to be identified.