Background: Recurrent pregnancy loss (RPL) occurs in 3–5% in about 30% of cases no cause can be found. Women
with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women,
higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was
to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic
circulation of pro-inflammatory molecules able to induce endometrial inflammation.
Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss
Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent
51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled
women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering
STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20
healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were
investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1β and IL-18 by ELISA, respectively.
Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS
(P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial
expression of Nalp-3, caspase-1 and IL-1β was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001,
respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association
between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in
RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be
statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women.
Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers,
potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis.
Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and
- intestinal permeability
- recurrent pregnancy