Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and
inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial
infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional
resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic
inflammation. In particular, bacterial products such as
lipopolysaccharide (LPS), also known as
endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the
inflammation further. The known need of microbes for free
iron can explain the
iron dysregulation that accompanies PE. We describe the main routes of
infection (gut, oral, and
urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic
biomarker of "
preeclampsia" that we assessed has, in fact, also been shown to be raised in response to
infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as
endotoxemia or
toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial
endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for
ulcers and other diseases that were previously considered to lack one.