99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: controversial aspects of the 'hygiene hypothesis'.

The 'hygiene hypothesis' proposes that the epidemic of allergic and autoimmune diseases is due to changes in the interactions between humans and the microbes of their ecosystem. This theory apparently does not explain (i) why allergic asthma is rising in 'unhygienic' American inner cities; (ii) why allergic diseases are less prevalent among migrants' children living in European big cities; (iii) why infections with airborne viruses do not 'protect' from allergic sensitization; (iv) why the inverse association between some infections (e.g. hepatitis A virus) and allergic diseases has been reproduced in some populations, but not in others; and (v) why probiotics are not effective in the prevention and therapy of allergic diseases. These challenging questions are useful starting points to improve our understanding of the hypothesis, and to identify among the infectious agents those really responsible for a protective influence against atopic and autoimmune diseases.