Bugs versus bugs: probiotics, microbiome and allergy.

exposure to infections. Although exposure to infections may be one source of immune education, the most extensive interaction of the human body with microbes occurs within our own gut, which, in addition to being the site of greatest bacterial colonization, is also the largest lymphoid organ in the body. Over 40 years ago, it was reported that germ-free status resulted in spontaneous allergy and anaphylaxis to dietary milk in rabbits [8] , suggesting that the microbiota is important for actively suppressing allergic sensitization and supporting the concept of ‘good bugs’ that could be used therapeutically. It has been proposed that a change in the constituents of the intestinal microbiota promotes allergic disease, a concept supported by recent preclinical data [9] . Using culture-based approaches to studying the human microbiome, there has been a lack of consistent findings comparing healthy to atopic infants [10, 11] . However, the vast majority of commensal bacteria cannot be cultured and are not represented in such approaches. The development of highthroughput genomic approaches for quantifying taxonomic units has been used to study stool samples from atopic infants compared to healthy controls, with a finding of reduced diversity and dysbiosis in allergic disease [12, 13] . Readers are referred to Garn et al. [14] for a comprehensive review of the current state of microbiome research in allergic disease. Studies on larger birth cohorts are needed to definitively answer the question of how changes in the microbiome precede the development of atopic disease. Advances in sequencing techniques now Probiotics, defined as ‘live organisms which, when administered in adequate amounts, confer a health benefit to the host’ [1] have a long history of human use, such as the ingestion of fermented milk products for health purposes. Commonly used probiotics include Lactobacillus or Bifidobacterium species, which have effects on the immune system and intestinal barrier function that support their use in the prevention or treatment of immune-mediated disorders [2–4] . It remains poorly understood, however, how probiotics actually interact with our commensal bacteria. The intestine, particularly the large intestine, is heavily colonized and commensal bacteria outnumber human cells by a factor of 10 to 1. The intestinal microbiota plays a key role in the maintenance of mucosal health: it helps to metabolize nutrients, produce shortchain fatty acids required for epithelial metabolism and has broad-ranging effects on the mucosal barrier, immune function and metabolism [5] . Manipulation of health by altering the microbiome was first systematically applied to livestock, where both antibiotics and probiotics have been used to promote weight gain [6] .