The role of microbial byproducts in protection against immunological disorders and the hygiene hypothesis.

Over the past three decades the incidence of allergic disorders and autoimmune diseases has risen and this trend is particularly prominent in developed nations. The hygiene hypothesis suggests that as a living environment becomes more sanitized, children are not exposed to microbial and parasitic stimulations that were once commonly acquired since early in life, leading to a lack of immune sensitization tending towards T helper 2 (Th2) dominance. This postulation is sufficient to explain allergic disorders, which mostly result from hyper Th2 responses, but inadequate to explain the increase in Th1 or Th17-based autoimmunity. Recent advances in experimental mouse models revealed that stimulation of Toll-like receptors (TLRs) by pathogen-associated molecular patterns could reduce symptoms of allergic airway disease and prevent the onset of autoimmunity. The underlying mechanism for the protective effects of TLR ligands is currently under intense investigation and there are indications that IL-10-producing B cells, regulatory T cells, and innate immune cells play an important role during this process. The finding that early exposure to microbial byproducts contributes to the modulation of immunological disorders may once again modify our interpretation of the hygiene hypothesis.