The Vaginal Community State Types Microbiome-Immune Network as Key Factor for Bacterial Vaginosis and Aerobic Vaginitis

Francesco De Seta, Giuseppina Campisciano, Nunzia Zanotta, Giuseppe Ricci, Manola Comar, Francesco De Seta, Giuseppina Campisciano, Nunzia Zanotta, Giuseppe Ricci, Manola Comar

Abstract

Regarding bacterial vaginosis (BV), the relevance of the vaginal microbiota to the women's health fulfills a key role, but knowledge gaps regarding aerobic vaginitis (AV) exist. This study aims to characterize vaginal microbiome and its relationship with the local immune mediators, providing an opportunity to define the link between vaginal commensal microorganisms and opportunistic pathogens in the relation of a given vaginal community state type (CST). A total of 90 vaginal samples from Caucasian asymptomatic women of reproductive age (18-40 years) attending the yearly examination and not reporting any vaginal complaints were retrospectively evaluated for microbiome assessment and immune factor dosage. The samples were tested by the Ion Torrent PGM and the Luminex Bio-Plex technologies for the analysis of microbiome and immune factors, respectively. In our study, the CST classification together with the local immune response profiling represented a good predictive indicator of the vaginal health, suggesting that the predominance of a specific Lactobacillus and its relative abundance are pivotal elements to maintain a physiologic status. A vaginal colonization from Bifidobacterium may absolve a protective role similar to that of Lactobacillus, corresponding to a newly identified CST, although studies are needed to better clarify its clinical significance. Moreover, within each CST, a different pattern of inflammation is activated and orchestrated both by the dominant Lactobacillus spp. and by specific non-Lactobacillus bacteria and can give insights into the pathogenic mechanisms. In conclusion, this study contributes to the characterization of vaginal dysbiosis, reshaping this concept by taking into consideration the CST profiling, local immune marker, and immune-microbial network.

Keywords: Bifidobacteria; Lactobacillus species; immune proteins; vaginal community state types; vaginal microbiome.

Copyright © 2019 De Seta, Campisciano, Zanotta, Ricci and Comar.

Figures

FIGURE 1
FIGURE 1
Generic marker of dysbiosis. According to the Pearson correlation score, M-CSF significantly (FDR p-value <0.001) correlated with several microorganisms. The association was calculated by means of the observation_metadata_correlation.py script on the rarefied otu_table.biom (5,000 reads/sample). The amount of M-CSF also varied based on the community state type (CST). The comparisons were performed by means of a Kruskal–Wallis one-way analysis of variance. When a significant p-value was observed (p < 0.05), a multiple comparison test was used to determine which groups were different. The data are shown as the mean value ±standard error of the mean (SEM). Pearson scores for every bacterial species are shown in brackets. FDR, false discovery rate; M-CSF, macrophage colony-stimulating factor. ∗p < 0.05.
FIGURE 2
FIGURE 2
Inflammasome-dependent pathway. According to the Pearson correlation score, components belonging to the inflammasome complex significantly (FDR p-value <0.001) correlated with several microorganisms. The association was calculated by means of the observation_metadata_correlation.py script on the rarefied otu_table.biom (5,000 reads/sample). The amount of IL-1α and IL-18 varied based on the community state type (CST). The comparisons were performed by means of a Kruskal–Wallis one-way analysis of variance. When a significant p-value was observed (p < 0.05), a multiple comparison test was used to determine which groups were different. The data are shown as the mean value ± standard error of the mean (SEM). Pearson scores for every bacterial species are shown in brackets. FDR, false discovery rate. ∗p < 0.05, ∗∗∗p < 0.001.
FIGURE 3
FIGURE 3
Inflammasome-independent pathway. According to the Pearson correlation score, some pro-inflammatory soluble immune factors (FDR p-value <0.001) correlated with Lactobacillus iners and Ureaplasma parvum. The association was calculated by means of the observation_metadata_correlation.py script on the rarefied otu_table.biom (5,000 reads/sample). The amount of these molecules did not vary based on the community state type (CST). The comparisons were performed by means of a Kruskal–Wallis one-way analysis of variance. When a significant p-value was observed (p < 0.05), a multiple comparison test was used to determine which groups were different. The data are shown as the mean value ±standard error of the mean (SEM). Pearson scores for every bacterial species are shown in brackets. FDR, false discovery rate.

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