Abstract
The discovery that microorganisms can be etiologic agents of disease has driven clinical, research and public health efforts to reduce exposure to bacteria. However, despite extensive campaigns to eradicate pathogens (via antibiotics, vaccinations, hygiene, sanitation, etc.), the incidence and/or severity of multiple immune-mediated diseases including, paradoxically, infectious disease have increased in recent decades. We now appreciate that most microbes in our environment are not pathogenic, and that many human-associated bacteria are symbiotic or beneficial. Notably, recent examples have emerged revealing that the microbiome augments immune system function. This review will focus on how commensal-derived signals enhance various aspects of the host response against pathogens. We suggest that modern lifestyle advances may be depleting specific microbes that enhance immunity against pathogens. Validation of the notion that absence of beneficial microbes is a risk factor for infectious disease may have broad implications for future medical practices.