Spontaneous miscarriage is the most common adverse pregnancy outcome in humans and occurs in 15-20% of all recognized pregnancies. High psychosocial stress perception has long been recognized as a threat to pregnancy maintenance and accumulating evidence supports that stress affects maternal adaptation to pregnancy and subsequently impedes fetomaternal tolerance. This review strongly focuses on the role of microbial products within the stress-induced signalling cascade, linking the disequilibrium of the endogenous microflora to immune activation and pregnancy loss. The stress signalling cascade utilizes the presence of lipopolysaccharide (LPS), which acts as a danger signal via Toll like receptor 4. Physiologically, the intestinal microflora provides a source for endogenous LPS, i.e. during the stress response, and psychosocial stress challenge in mice enhances the gastrointestinal permeability and bacterial uptake from the gut. Clearly, these novel insights not only deepen our understanding of mechanisms involved in the stress response cascade, but also initiate a renaissance of therapeutic intervention strategies, aiming to modulate the intestinal flora by probiotic bacteria. In turn, intestinal barrier function may be enhanced and mediators of immune tolerance may be restored, i.e. in the context of reproduction.
