Background: Gender reassignment surgery is a procedure some transgender women (TW) undergo for genderaffirming purposes. This often includes the construction of a neovagina using existing penile and scrotal tissue and/ or a sigmoid colon graft. There are limited data regarding the composition and function of the neovaginal microbiome representing a major gap in knowledge in neovaginal health. Results: Metaproteomics was performed on secretions collected from the neovaginas (n = 5) and rectums (n = 7) of TW surgically reassigned via penile inversion/scrotal graft with (n = 1) or without (n = 4) a sigmoid colon graft extension and compared with secretions from cis vaginas (n = 32). We identified 541 unique bacterial proteins from 38 taxa. The most abundant taxa in the neovaginas were Porphyromonas (30.2%), Peptostreptococcus (9.2%), Prevotella (9.0%), Mobiluncus (8.0%), and Jonquetella (7.2%), while cis vaginas were primarily Lactobacillus and Gardnerella. Rectal samples were mainly composed of Prevotella and Roseburia. Neovaginas (median Shannon's H index = 1.33) had higher alpha diversity compared to cis vaginas (Shannon's H = 0.35) (p = 7.2E−3, Mann-Whitney U test) and were more similar to the non-Lactobacillus dominant/polymicrobial cis vaginas based on beta diversity (perMANOVA, p = 0.001, r 2 = 0.342). In comparison to cis vaginas, toll-like receptor response, amino acid, and shortchain fatty acid metabolic pathways were increased (p < 0.01), while keratinization and cornification proteins were decreased (p < 0.001) in the neovaginal proteome. Conclusions: Penile skin-lined neovaginas have diverse, polymicrobial communities that show similarities in composition to uncircumcised penises and host responses to cis vaginas with bacterial vaginosis (BV) including increased immune activation pathways and decreased epithelial barrier function. Developing a better understanding of microbiome-associated inflammation in the neovaginal environment will be important for improving our knowledge of neovaginal health.
The adaptive potential of invasive species is thought to decrease during founding events due to reduced genetic diversity, limiting the new population’s ability to colonize novel habitats. Barbary ground squirrels (Atlantoxerus getulus) were purportedly introduced as a single breeding pair to the island of Fuerteventura but have expanded to over a million individuals spread across the island in just over 50 years. We estimated the number of founders and measured the level of genetic diversity in this population using the mitochondrial displacement loop and microsatellite markers. Island samples (n = 19) showed no variation in the d-loop, suggesting a single founding female, while Moroccan samples (n = 6) each had unique mitochondrial haplotypes. The microsatellite data of the island population (n = 256 individuals) revealed a small effective population size, low levels of heterozygosity, and high levels of inbreeding, supporting a founding population size of two to three individuals. Our results suggest that A. getulus has undergone an intense genetic bottleneck during their colonization of the island. They are one of the few species where introduction effort does not explain invasion success, although further investigation may explain how they have avoided the worst expected effects following an extreme genetic bottleneck.
Introduction Bacterial vaginosis (BV), characterized by Lactobacillus depletion and replacement by facultative or anaerobic bacteria, impacts up to 30% of women and associates with negative reproductive health outcomes. We used a systems immunology approach to investigate cellular and molecular inflammation associated with BV. Methods Matched cervical cytobrush and cervicovaginal lavage were collected from BV− (n=16) and BV+ (n=11) women. Cytobrushes were immunophenotyped by flow cytometry and lavages were analyzed by tandem mass spectrometry. Differences in immune cell levels were evaluated with Mann-Whitney U tests, and assessed against host and bacterial proteins using Spearman’s Rank correlations. Results There were no clinical or demographic differences between BV+ and BV− women, including age (range 22–49), birth control use and STI history. Proteomic analysis identified 1085 human proteins and 516 bacterial proteins from 14 genera, including Lactobacillus, Gardnerella, and Mobiluncus. Long living neutrophils (CD49d+) were significantly increased in BV+ women (p=0.0005), and associated with cell adhesion (p=4.04E-5), T cell mediated immunity (p=0.004), and regulation of myeloid differentiation (p=8.63E-16) pathways. CD49+ neutrophils correlated positively with Mobiluncus (p=0.040, R2=0.49) and negatively with Lactobacillus (p=0.035, R2=−0.498). Discussion This data indicates that cervical neutrophil survival is increased in women with BV. These cells associated with anaerobic bacteria and molecular pathways of immune activation. Studies are ongoing to delineate the relationship between BV-associated bacteria and neutrophil functionality, which may have implications for BV treatment.
Background: Cervicovaginal inflammation has been linked to negative reproductive health outcomes including acquisition of HIV, other sexually transmitted infections, and cervical carcinogenesis. While changes to the vaginal microbiome have been linked to genital inflammation, the molecular relationships between the functional components of the microbiome with cervical immunology in the reproductive tract are understudied, limiting our understanding of mucosal biology that may be important for reproductive health.Results: In this study we used a multi’-omics approach to profile cervicovaginal samples collected from 43 Canadian women to characterize host, immune, functional microbiome and metabolome features of cervicovaginal inflammation. We demonstrate that inflammation is associated with lower amounts of L. crispatus and increased levels of cervical antigen presenting cells (APCs). Proteomic analysis showed an upregulation of pathways related to neutrophil degranulation, complement, and leukocyte migration, with decreased levels of cornified envelope and cell-cell adherens junctions. Functional microbiome analysis showed reductions to carbohydrate metabolism and lactic acid, with increases of xanthine and other metabolites. Bayesian network analysis linked L. crispatus with glycolytic and nucleotide metabolism, succinate and xanthine, and epithelial proteins SCEL and IVL as major molecular features associated with pro-inflammatory cytokines and increased APCs.Conclusions: This study identified key molecular and immunological relationships with cervicovaginal inflammation, including increased APCs, bacterial metabolism, and proteome alterations that underlie inflammation. As APCs are involved in HIV transmission, parturition, and cervical cancer progression, further studies are needed to explore the interactions between these cells, bacterial metabolism, mucosal immunity, and their relationship to reproductive health.
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