The germ theory revisited: A noncentric view on infection outcome

The germ theory states that pathogenic microorganisms are responsible for causing infectious diseases. The theory is inherently microbe-centric and does not account for variability in disease severity among individuals and asymptomatic carriership—two phenomena indicating an important role for host variability in infection outcome. The basic tenet of the germ theory was recently challenged, and a radically host-centric paradigm referred to as the “full-blown host theory” was proposed. According to this view, the pathogen is reduced to a passive environmental trigger, and the development of disease is instead due to pre-existing immunodeficiencies of the host. Here, we consider the factors that determine disease severity using established knowledge concerning evolutionary biology, microbial pathogenesis, and host–pathogen interactions. We note that the available data support a noncentric view that recognizes key roles for both the causative microbe and the host in dictating infection outcome.