“The ‘hygiene hypothesis’ takes a number of forms which are not exclusive, but have yet to be articulated as a unifying concept. An inverse relationship between parasite infection and immune disorders was first suggested by Greenwood, who noted the low incidence of rheumatoid arthritis in West Africa , and then showed that mice and rats infected with rodent malaria were protected from autoimmune disease [9, 10]. Subsequently, the hygiene hypothesis became linked explicity to the setting of more developed countries when Strachan postulated that early-life exposure to common childhood infections protected younger siblings in larger families from developing allergies such as hay fever [11, 12]. At that time, soon after the emergence of the paradigm of opposing T helper type 1 (Th1) and Th2 arms of the immune system , this finding was interpreted as Th1-promoting viral and bacterial infections ‘educating’ the young immune system away from excessive and allergy-promoting Th2 responses. The core concept of infections imprinting the developing immune system has become embedded in most versions of the hygiene hypothesis, but the mechanistic explanation of opposing Th1/Th2 lineages has, over time, proved untenable.”
In contrast to the Th2-mediated allergies [mediated through immunoglobulin (Ig)E, mast cells and eosinophils], other modern maladies such as type I diabetes, multiple sclerosis and Crohn’s disease are driven by Th1 responses, or by the more recently defined Th17 cells . Critically, these Th1/17 conditions have been increasing in prevalence in high-income countries as sharply as Th2-dependent allergies. For example, the incidence of type I diabetes is increasing year-on-year at the rate of 3·4% , in tandem with the rise in asthma . Tellingly, the age of diabetes onset has become significantly younger, indicating that this disease is gaining in force within the population. Similar patterns have been observed for multiple sclerosis and Crohn’s disease, and it is difficult to reconcile the accentuation of these diseases with reduced exposure to Th1-stimulating microbes in early life.