The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth.

Preterm birth (PTB, <37 completed weeks' gestation) is one of the leading obstetrical problems in the United States, affecting approximately one of every nine births. Even more concerning are the persistent racial disparities in PTB, with particularly high rates among African Americans. There are several recognized pathophysiologic pathways to PTB, including infection and/or exaggerated systemic or local inflammation. Intrauterine infection is a causal factor linked to PTB thought to result most commonly from inflammatory processes triggered by microbial invasion of bacteria ascending from the vaginal microbiome. Trials to treat various infections have shown limited efficacy in reducing PTB risk, suggesting that other complex mechanisms, including those associated with inflammation, may be involved in the relationship between microbes, infection, and PTB. The complement system, a key mediator of the inflammatory response, is an innate defense mechanism involved in both normal physiologic processes that occur during pregnancy implantation and processes that promote the elimination of pathogenic microbes. Recent research has demonstrated an association between this system and PTB. The purpose of this article is to present a mechanistic model of inflammation-associated PTB, which hypothesizes a relationship between the microbiome and dysregulation of the complement system. Exploring the relationships between the microbial environment and complement biomarkers may elucidate a potentially modifiable biological pathway to PTB.