Interaction between Cervical Microbiota and Host Gene Regulation in Caesarean Section Scar Diverticulum

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

35900092

DOI Digital object identifier for electronic documents.

https://doi.org/10.1128/spectrum.01676-22

URI

Authors

Yang X, Pan X, Li M, Zeng Z, Guo Y, Chen P, Liang X, Chen P, Liu G

Journal

Microbiology spectrum

Year

2022

Keywords:

cesarean section scar diverticulum, gene regulation, host-microbiota interaction, microbiome

Cesarean section scar diverticulum (CSD) has become a formidable obstacle preventing women receiving CS from reproducing. However, the pathogenesis of CSD remains unexplored. In this study, we characterized the cervical microbiota, metabolome, and endometrial transcriptome of women with CSD. Based on the 16s rRNA results of cervical microbes, the microbial diversity in the CSD group was higher than that in the control group. Lactobacillus were significantly decreased in the CSD group and were mutually exclusive with potentially harmful species (Sphingomonas, Sediminbacterium, and Ralstonia) abnormally elevated in CSD. The microbiota in the CSD group exhibited low activity in carbohydrate metabolism and high activity in fatty acid metabolism, as confirmed by the metabolomic data. The metabolomic characterization identified 6,130 metabolites, of which 34 were significantly different between the two groups. In the CSD group, N-(3-hydroxy-eicosanoid)-homoserine lactone and Ternatin were significantly increased, in addition to the marked decrease in fatty acids due to high consumption. N-(3-hydroxy-eicosanoyl)-homoserine lactone is a regulator that promotes abnormal apoptosis in a variety of cells, including epithelial cells and vascular endothelial cells. This abnormal apoptosis of endometrial epithelial cells and neovascularization was also reflected in the transcriptome of the endometrium surrounding the CSD. In the endometrial transcriptome data, the upregulated genes in the CSD group were active in negatively regulating the proliferation of blood vessel endothelial cells, endothelial cells, and epithelial cells. This alteration in the host's endometrium is most likely influenced by the abnormal microbiota, which appears to be confirmed in the results by integrating host transcriptome and microbiome data. For the first time, this study described the abnormal activity characteristics of microbiota and the mechanism of host-microbiota interaction in CSD. IMPORTANCE Cesarean section scar diverticulum (CSD) has become a formidable obstacle preventing women receiving CS from reproducing. In this study, we revealed that potentially harmful microbes do have adverse effects on the host endometrium. The mechanism of these adverse effects includes the inhibition of the activity of beneficial bacteria such as lactobacilli, consumption of protective metabolites of the endometrium, and also the production of harmful metabolites. In the present study, we elucidated the mechanism from the perspectives of microbial, metabolic, and host responses, providing an important rationale to design preventive and therapeutic strategies for CSD.

Experiment 1

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Curated date: 2024/03/17

Curator: Eve10111

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Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Endometrium , Uterine epithelium Tunica mucosa (endometrium),Tunica mucosa uteri,Uterine endometrium,Uterine mucosa,Uterine mucous membrane,Endometrium,endometrium,Uterus epithelium,Uterine epithelium,uterine epithelium

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cesarean section caesarean section,Cesarean section,cesarean section

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Control

Group 1 name Corresponds to the case (exposed) group for case-control studies: Cesarean Section Diverticulum

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with a form of outpouching located in the anterior lower uterine cavity at the site of a cesarean section scar.

Group 0 sample size Number of subjects in the control (unexposed) group: 28

Group 1 sample size Number of subjects in the case (exposed) group: 24

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 Month

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased

Signature 1

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Curated date: 2024/03/17

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Source: figure 2

Description: Based on linear discriminant analysis (LDA), differential genus between the two groups were screened

Abundance in Group 1: increased abundance in Cesarean Section Diverticulum

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Bacteroides
Enterococcus
Escherichia/Shigella sp.
Gardnerella
Muribaculaceae
Paraburkholderia caballeronis
Prevotella
Ralstonia
Sphingomonas
Streptococcus

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Signature 2

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Source: figure 2

Description: Based on linear discriminant analysis (LDA), differential genus between the two groups were screened

Abundance in Group 1: decreased abundance in Cesarean Section Diverticulum

NCBI	Quality Control	Links
Lactobacillus
Faecalibaculum

Revision editor(s): Eve10111