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. 2020 Jun;83(6):e13235.
doi: 10.1111/aji.13235. Epub 2020 Apr 9.

Pregnancy associates with alterations to the host and microbial proteome in vaginal mucosa

Christina Farr Zuend  1   2 , Nicole H Tobin  3 , Trisha Vera  1   2 , Lani Kotyrba  1   2 , Laura Noël-Romas  1   2 , Kenzie Birse  1   2 , Sarah Mutch  1   2 , Fan Li  3 , David Lee  3 , Stuart McCorrister  4 , Garrett Westmacott  4 , Grace M Aldrovandi  3 , Adam D Burgener  2   5   6   7
Affiliations

Pregnancy associates with alterations to the host and microbial proteome in vaginal mucosa

Christina Farr Zuend et al. Am J Reprod Immunol. 2020 Jun.

Abstract

Problem: Pregnant women are at increased risk of HIV acquisition, but the biological mechanisms contributing to this observation are not well understood.

Method of study: Here, we assessed host immune and microbiome differences in the vaginal mucosa of healthy pregnant and non-pregnant women using a metaproteomics approach. Cervicovaginal lavage (CVL) samples were collected from 23 pregnant and 25 non-pregnant women.

Results: Mass spectrometry analysis of CVL identified 550 human proteins and 376 bacterial proteins from 11 genera. Host proteome analysis indicated 56 human proteins (10%) were differentially abundant (P < .05) between pregnant and non-pregnant women, including proteins involved in angiogenesis (P = 3.36E-3), cell movement of phagocytes (P = 1.34E-6), and permeability of blood vessels (P = 1.27E-4). The major bacterial genera identified were Lactobacillus, Gardnerella, Prevotella, Megasphaera, and Atopobium. Pregnant women had higher levels of Lactobacillus species (P = .017) compared with non-pregnant women. Functional pathway analysis indicated that pregnancy associated with changes to bacterial metabolic pathway involved in energy metabolism, which were increased in pregnant women (P = .035).

Conclusion: Overall, pregnant women showed differences in the cervicovaginal proteome and microbiome that may be important for HIV infection risk.

Keywords: HIV; microbiome; pregnancy; proteomics.

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Figures

Figure 1
Figure 1
Cervicovaginal proteome pathways that are differentially abundant between pregnant and non‐pregnant women. A, Volcano plot of all proteins identified comparing pregnant and non‐pregnant women using two‐tailed independent t tests. B, Hierarchical clustering of differentially abundant (P < .05) proteins between pregnant and non‐pregnant women. Proteins that are overabundant are represented in the heat map in red and those that are underabundant are represented in blue. Pregnancy status and ectopy status are shown. Proteins involved in biofunctions significantly associated with pregnancy (angiogenesis including vasculogenesis and blood vessel permeability; movement of leukocytes; activation of cells; and immune factors) are highlighted. A total of 56 proteins were differentially abundant between pregnant and non‐pregnant women, with 27 overabundant in pregnant women and 29 underabundant. C, Principal component analysis of 27 immune‐related factors that were significantly different between pregnant and non‐pregnant women. Boxplots depicting log2 normalized protein abundance for immune (D), angiogenesis (E), and pregnancy (F) factors that were differentially abundant (P < .05) between pregnant and non‐pregnant women
Figure 2
Figure 2
The microbiome in pregnant women is dominated by Lactobacillus. A, Taxa proportion plots of each individual based on pregnancy status detected by MS Lactobacillus is displayed to the species level for the two most abundant species detected, L iners and L crispatus. B, Summary of distribution of bacterial taxa by pregnancy status. The average percentages for the top three bacterial taxa are shown. C, Normalized protein abundance for all Lactobacillus species in pregnant and non‐pregnant women. P value was calculated using the Mann‐Whitney U test. D, Normalized protein abundance for all Lactobacillus species in pregnant women compared with gestational age. Spearman's r = .2862, P = .1855. E, Shannon's Diversity Index by pregnancy status. Wilcoxon P value is shown. F, Principal component analysis of all bacterial proteins detected in pregnant and non‐pregnant women
Figure 3
Figure 3
Functional microbiome pathway analysis. A, ko‐level bacterial functions in pregnant and non‐pregnant women. B, Carbon fixation pathways in prokaryotes are increased in pregnant women. C, Bacterial genera that contribute proteins to carbon fixation pathways in prokaryotes in pregnant and non‐pregnant women. D, Principal component analysis of ko‐level bacterial functional data with pregnancy status. E, Principal component analysis of ko‐level bacterial function data with both pregnancy and microbiome (LD vs nLD) status. Lines indicate bacterial proteins that are driving the variances
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