Evidence that intra-amniotic infections are often the result of an ascending invasion – a molecular microbiological study

Abstract

Background Microbial invasion of the amniotic cavity resulting in intra-amniotic infection is associated with obstetrical complications such as preterm labor with intact or ruptured membranes, cervical insufficiency, as well as clinical and histological chorioamnionitis. The most widely accepted pathway for intra-amniotic infection is the ascension of microorganisms from the lower genital tract. However, hematogenous dissemination of microorganisms from the oral cavity or intestine, retrograde seeding from the peritoneal cavity through the fallopian tubes, and introduction through invasive medical procedures have also been suggested as potential pathways for intra-amniotic infection. The primary reason that an ascending pathway is viewed as most common is that the microorganisms most often detected in the amniotic fluid are those that are typical inhabitants of the vagina. However, thus far, no studies have shown that microorganisms in the amniotic cavity are simultaneously present in the vagina of the woman from which they were isolated. The objective of the study was to determine the frequency with which microorganisms isolated from women with intra-amniotic infection are also present in the lower genital tract. Methods This was a cross-sectional study of women with intra-amniotic infection with intact membranes. Intra-amniotic infection was defined as a positive culture and elevated concentrations of interleukin-6 (IL-6) (>2.6 ng/mL) in amniotic fluid and/or acute histologic chorioamnionitis and funisitis. Microorganisms isolated from bacterial cultures of amniotic fluid were taxonomically identified through matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and 16S ribosomal RNA (rRNA) gene sequencing. Vaginal swabs were obtained at the time of amniocentesis for the identification of microorganisms in the lower genital tract. The overall bacterial profiles of amniotic fluids and vaginal swabs were characterized through 16S rRNA gene sequencing. The bacterial profiles of vaginal swabs were interrogated for the presence of bacteria cultured from amniotic fluid and for the presence of prominent (>1% average relative abundance) operational taxonomic units (OTUs) within the overall 16S rRNA gene bacterial profiles of amniotic fluid. Results (1) A total of 75% (6/8) of women had bacteria cultured from their amniotic fluid that are typical residents of the vaginal ecosystem. (2) A total of 62.5% (5/8) of women with bacteria cultured from their amniotic fluid also had these bacteria present in their vagina. (3) The microorganisms cultured from amniotic fluid and also detected in the vagina were Ureaplasma urealyticum, Escherichia coli, and Streptococcus agalactiae. (4) 16S rRNA gene sequencing revealed that the amniotic fluid of women with intra-amniotic infection had bacterial profiles dominated by Sneathia, Ureaplasma, Prevotella, Lactobacillus, Escherichia, Gardnerella, Peptostreptococcus, Peptoniphilus, and Streptococcus, many of which had not been cultured from the amniotic fluid samples. (5) Seventy percent (7/10) of the prominent (>1% average relative abundance) OTUs found in amniotic fluid were also prominent in the vagina. Conclusion The majority of women with intra-amniotic infection had bacteria cultured from their amniotic fluid that were typical vaginal commensals, and these bacteria were detected within the vagina at the time of amniocentesis. Molecular microbiological interrogation of amniotic fluid from women with intra-amniotic infection revealed that the bacterial profiles of amniotic fluid were largely consistent with those of the vagina. These findings indicate that ascension from the lower genital tract is the primary pathway for intra-amniotic infection.

Microorganisms associated with intraamniotic infection among women with preterm birth at Ruhengeri Referral Hospital, Rwanda: A case-control study

“…Some microorganisms were isolated from women with preterm birth and excluded from women that had carried their pregnancy to a full-term birth. Similar ndings reported that Escherichia coli and Streptococcus species were isolated from women with intraamniotic infections [17]. The current study compared the microbial differences between women with preterm and women with full-term delivery.…”

New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future?

“…A pioneering study has tested the use of VMT from healthy donors as therapeutic alternative for patients suffering from symptomatic, intractable and recurrent vaginosis, and reported positive treatment outcomes [160]. Since the uterine colonisation of microorganisms by vaginal-cervical ascension is known [35,36], VMT could open up a future way for managing endometrial dysbiosis. In addition, what about uterine microbiota transfer (UMT)?…”

“…Ascension of radioactively labelled macrospheres from vagina to the uterus by a 'uterine peristaltic pump' activity was shown [32,33], highlighting the most probable way for bacterial route into the uterus. Indeed, different studies suggest that microbial composition is highly influenced by the vaginal microbes [8,11,[34][35][36].…”

Innate Immune Mechanisms to Protect Against Infection at the Human Decidual-Placental Interface

“…Defense mechanisms in the cervix, such as the production of mucus and antimicrobial peptides (AMP), limit ascending infection from pathogens present in the lower genital tract, that otherwise may access the uterine cavity ( 6 ). However, some pathogens can escape antimicrobial strategies at the cervix and ascend to the uterus, where they can bypass the fetal membranes and lead to the inflammation of the membranes- also known as chorioamnionitis- and infection of the amniotic fluid ( 7 , 8 ). Pathologic and immune features of chorioamnionitis and intra-amniotic infection are generally associated with bacterial invasion and inflammation [refer to ( 8 , 9 ) for a comprehensive review on these mechanisms].…”