Maternal Microbe-Specific Modulation of Inflammatory Response in Extremely Low-Gestational-Age Newborns

Laboratory of Genital Tract Biology, Department of Obstetrics and Gynecology, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA.
mBio (Impact Factor: 6.79). 12/2011; 2(1):e00280-10. DOI: 10.1128/mBio.00280-10
Source: PubMed


The fetal response to intrauterine inflammatory stimuli appears to contribute to the onset of preterm labor as well as fetal injury, especially affecting newborns of extremely low gestational age. To investigate the role of placental colonization by specific groups of microorganisms in the development of inflammatory responses present at birth, we analyzed 25 protein biomarkers in dry blood spots obtained from 527 newborns delivered by Caesarean section in the 23rd to 27th gestation weeks. Bacteria were detected in placentas and characterized by culture techniques. Odds ratios for having protein concentrations in the top quartile for gestation age for individual and groups of microorganisms were calculated. Mixed bacterial vaginosis (BV) organisms were associated with a proinflammatory pattern similar to those of infectious facultative anaerobes. Prevotella and Gardnerella species, anaerobic streptococci, peptostreptococci, and genital mycoplasmas each appeared to be associated with a different pattern of elevated blood levels of inflammation-related proteins. Lactobacillus was associated with low odds of an inflammatory response. This study provides evidence that microorganisms colonizing the placenta provoke distinctive newborn inflammatory responses and that Lactobacillus may suppress these responses.

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Available from: Raina Fichorova
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    • "Through the change of pH or through direct bactericidal properties, such products and practices may affect the composition of the normal vaginal microbiome, which is essential for the healthy mucosal environment and protection against yeast infection or other sexually transmitted pathogens. Vaginal lactobacilli are also important for having a healthy pregnancy and may prevent premature delivery and illness in the newborns (2). The disturbance of the normal microbiome, a condition called bacterial vaginosis (BV), is associated with significant risks for women's health as well as inflammatory complications in the newborn (3), while the presence of Lactobacillus has been associated with lower risk of inflammation (2). "
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    ABSTRACT: Over-the-counter (OTC) feminine hygiene products come with little warning about possible side effects. This study evaluates in-vitro their effects on Lactobacillus crispatus, which is dominant in the normal vaginal microbiota and helps maintain a healthy mucosal barrier essential for normal reproductive function and prevention of sexually transmitted infections and gynecologic cancer. A feminine moisturizer (Vagisil), personal lubricant, and douche were purchased OTC. A topical spermicide (nonoxynol-9) known to alter the vaginal immune barrier was used as a control. L. crispatus was incubated with each product for 2 and 24h and then seeded on agar for colony forming units (CFU). Human vaginal epithelial cells were exposed to products in the presence or absence of L. crispatus for 24h, followed by epithelium-associated CFU enumeration. Interleukin-8 was immunoassayed and ANOVA was used for statistical evaluation. Nonoxynol-9 and Vagisil suppressed Lactobacillus growth at 2h and killed all bacteria at 24h. The lubricant decreased bacterial growth insignificantly at 2h but killed all at 24h. The douche did not have a significant effect. At full strength, all products suppressed epithelial viability and all, except the douche, suppressed epithelial-associated CFU. When applied at non-toxic dose in the absence of bacteria, the douche and moisturizer induced an increase of IL-8, suggesting a potential to initiate inflammatory reaction. In the presence of L. crispatus, the proinflammatory effects of the douche and moisturizer were countered, and IL-8 production was inhibited in the presence of the other products. Some OTC vaginal products may be harmful to L. crispatus and alter the vaginal immune environment. Illustrated through these results, L. crispatus is essential in the preservation of the function of vaginal epithelial cells in the presence of some feminine hygiene products. More research should be invested toward these products before they are placed on the market.
    Full-text · Article · Feb 2013 · Microbial Ecology in Health and Disease
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    • "Increased levels of inflammatory cytokines and chemokines have been found in the cervical and vaginal secretions of women with trichomoniasis [3], and some have prognostic value in women with preterm delivery [59], [60]. On the other hand placental inflammation is associated with inflammatory responses in the fetus and especially in extremely low gestation age newborns, which has been independently linked to a wide range of frequently occurring developmental problems in this clinical population [61], [62]. "
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    ABSTRACT: Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted implications to the human host. Among them, Trichomonas vaginalis, a parasite adapted to the human genitourinary tract, infects globally ∼250 million each year rendering them more susceptible to devastating pregnancy complications (especially preterm birth), HIV infection and HPV-related cancer. While first-line antibiotic treatment (metronidazole) commonly kills the protozoan pathogen, it fails to improve reproductive outcome. We show that endosymbiotic Trichomonasvirus, highly prevalent in T. vaginalis clinical isolates, is sensed by the human epithelial cells via Toll-like receptor 3, triggering Interferon Regulating Factor -3, interferon type I and proinflammatory cascades previously implicated in preterm birth and HIV-1 susceptibility. Metronidazole treatment amplified these proinflammatory responses. Thus, a new paradigm targeting the protozoan viruses along with the protozoan host may prevent trichomoniasis-attributable inflammatory sequelae.
    Full-text · Article · Nov 2012 · PLoS ONE
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    • "Elizabeth Allred Alan Leviton Neuroepidemiology Unit Children's Hospital of Boston Boston, Massachusetts, USA Published 19 April 2011 Citation Fichorova, RN et al. 2011. "

    Full-text · Article · Mar 2011 · mBio
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