Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract
The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We t...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Public Library of Science
2017
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| Online Access: | http://hdl.handle.net/1721.1/107936 |
| _version_ | 1811080587135418368 |
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| author | Zevin, Alexander S. Xie, Irene Y. Birse, Kenzie Arnold, Kelly Romas, Laura Westmacott, Garrett Novak, Richard M. McCorrister, Stuart McKinnon, Lyle R. Cohen, Craig R. Mackelprang, Romel Lingappa, Jairam Klatt, Nichole R. Burgener, Adam D. Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Zevin, Alexander S. Xie, Irene Y. Birse, Kenzie Arnold, Kelly Romas, Laura Westmacott, Garrett Novak, Richard M. McCorrister, Stuart McKinnon, Lyle R. Cohen, Craig R. Mackelprang, Romel Lingappa, Jairam Klatt, Nichole R. Burgener, Adam D. Lauffenburger, Douglas A |
| author_sort | Zevin, Alexander S. |
| collection | MIT |
| description | The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity. |
| first_indexed | 2024-09-23T11:33:47Z |
| format | Article |
| id | mit-1721.1/107936 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:33:47Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1079362022-10-01T04:27:59Z Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract Zevin, Alexander S. Xie, Irene Y. Birse, Kenzie Arnold, Kelly Romas, Laura Westmacott, Garrett Novak, Richard M. McCorrister, Stuart McKinnon, Lyle R. Cohen, Craig R. Mackelprang, Romel Lingappa, Jairam Klatt, Nichole R. Burgener, Adam D. Lauffenburger, Douglas A Massachusetts Institute of Technology. Department of Biological Engineering Lauffenburger, Douglas A The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity. 2017-04-07T15:26:42Z 2017-04-07T15:26:42Z 2016-09 2016-06 Article http://purl.org/eprint/type/JournalArticle 1553-7374 1553-7366 http://hdl.handle.net/1721.1/107936 Zevin, Alexander S. et al. “Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract.” Ed. Guido Silvestri. PLOS Pathogens 12.9 (2016): e1005889. en_US http://dx.doi.org/10.1371/journal.ppat.1005889 PLOS Pathogens Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | Zevin, Alexander S. Xie, Irene Y. Birse, Kenzie Arnold, Kelly Romas, Laura Westmacott, Garrett Novak, Richard M. McCorrister, Stuart McKinnon, Lyle R. Cohen, Craig R. Mackelprang, Romel Lingappa, Jairam Klatt, Nichole R. Burgener, Adam D. Lauffenburger, Douglas A Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract |
| title | Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract |
| title_full | Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract |
| title_fullStr | Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract |
| title_full_unstemmed | Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract |
| title_short | Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract |
| title_sort | microbiome composition and function drives wound healing impairment in the female genital tract |
| url | http://hdl.handle.net/1721.1/107936 |
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