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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Fetal membrane bacterial load is increased in histologically confirmed inflammatory chorioamnionitis: A retrospective
Rochelle Hockney1, Gareth J Waring2, Gillian Taylor1
1School of Health and Life Sciences, Teesside University, Middlesbrough, TS1 3BX, UK; National Horizons Centre, Teesside University, 38 John Dixon Lane, Darlington, DL1 1HG, UK.
Introduction:
It is widely debated whether fetal membranes possess a genuine microbiome, and if bacterial presence and load is linked to inflammation. Chorioamnionitis is an inflammation of the fetal membranes. This research focussed on inflammatory diagnosed histological chorioamnionitis (HCA) and aimed to determine whether the bacterial load in fetal membranes correlates to inflammatory response, including histological staging and inflammatory markers in HCA.
Methods:
Fetal membrane samples were collected from patients with preterm spontaneous labour and histologically phenotyped chorioamnionitis (HCA; n = 12), or preterm (n = 6) and term labour without HCA (n = 6). The bacterial profile of fetal membranes was analysed by sequencing the V4 region of the 16S rRNA gene. Bacterial load was determined using qPCR copy number/mg of tissue. The association between bacterial load and bacterial profile composition was assessed using correlation analysis.
Results:
Bacterial load was significantly greater within HCA amnion (p = 0.002) and chorion (p = 0.042), compared to preterm birth without HCA. Increased bacterial load was positively correlated with increased histological staging (p = 0.001) and the expression of five inflammatory markers; IL8, TLR1, TLR2, LY96 and IRAK2 (p=<0.050). Bacterial profiles were significantly different between membranes with and without HCA in amnion (p = 0.012) and chorion (p = 0.001), but no differences between specific genera were detected.
Discussion:
Inflammatory HCA is associated with infection and increased bacterial load in a dose response relationship. Bacterial load is positively correlated with HCA severity and the TLR signalling pathway. Further research should investigate the bacterial load threshold required to generate an inflammatory response in HCA.
Insights
Increased bacterial load in fetal membranes correlates with histological chorioamnionitis (HCA) severity and inflammatory markers. This suggests infection drives HCA inflammation in a dose-dependent manner.
Area of Science:
- Obstetrics and Gynecology
- Microbiology
- Immunology
Background:
- The presence and role of a fetal membrane microbiome are debated.
- Chorioamnionitis (HCA) is a key cause of preterm birth, characterized by fetal membrane inflammation.
- The link between bacterial load and HCA severity requires further elucidation.
Purpose of the Study:
- To investigate the correlation between bacterial load in fetal membranes and histological chorioamnionitis (HCA).
- To assess the relationship between bacterial load, histological staging, and inflammatory markers in HCA.
Main Methods:
- Fetal membrane samples from HCA, preterm, and term labor groups were analyzed.
- Bacterial 16S rRNA gene sequencing determined microbial profiles.
- Quantitative PCR (qPCR) measured bacterial load (copy number/mg tissue).
Main Results:
- Significantly higher bacterial load in HCA amnion and chorion compared to controls.
- Positive correlation between bacterial load and HCA histological staging (p=0.001).
- Increased bacterial load associated with elevated inflammatory markers (IL8, TLR1, TLR2, LY96, IRAK2).
Conclusions:
- Histological chorioamnionitis (HCA) is linked to infection and increased bacterial load.
- Bacterial load demonstrates a dose-response relationship with HCA severity and TLR pathway activation.
- Further studies needed to define bacterial load thresholds triggering HCA inflammation.

