Cargando…

Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy

The vaginal microbiome (VMB) is a complex microbial community that is closely tied to reproductive health. Optimal VMB communities have compositions that are commonly defined by the dominance of certain Lactobacillus spp. and can remain stable over time or transition to non-optimal states dominated...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Christina Y., Diegel, Jenna, France, Michael T., Ravel, Jacques, Arnold, Kelly B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10446192/
https://www.ncbi.nlm.nih.gov/pubmed/37566641
http://dx.doi.org/10.1371/journal.pcbi.1011295
_version_ 1785094350096564224
author Lee, Christina Y.
Diegel, Jenna
France, Michael T.
Ravel, Jacques
Arnold, Kelly B.
author_facet Lee, Christina Y.
Diegel, Jenna
France, Michael T.
Ravel, Jacques
Arnold, Kelly B.
author_sort Lee, Christina Y.
collection PubMed
description The vaginal microbiome (VMB) is a complex microbial community that is closely tied to reproductive health. Optimal VMB communities have compositions that are commonly defined by the dominance of certain Lactobacillus spp. and can remain stable over time or transition to non-optimal states dominated by anaerobic bacteria and associated with bacterial vaginosis (BV). The ability to remain stable or undergo transitions suggests a system with either single (mono-stable) or multiple (multi-stable) equilibrium states, though factors that contribute to stability have been difficult to determine due to heterogeneity in microbial growth characteristics and inter-species interactions. Here, we use a computational model to determine whether differences in microbial growth and interaction parameters could alter equilibrium state accessibility and account for variability in community composition after menses and antibiotic therapies. Using a global uncertainty and sensitivity analysis that captures parameter sets sampled from a physiologically relevant range, model simulations predicted that 79.7% of microbial communities were mono-stable (gravitate to one composition type) and 20.3% were predicted to be multi-stable (can gravitate to more than one composition type, given external perturbations), which was not significantly different from observations in two clinical cohorts (HMP cohort, 75.2% and 24.8%; Gajer cohort, 78.1% and 21.9%, respectively). The model identified key microbial parameters that governed equilibrium state accessibility, such as the importance of non-optimal anaerobic bacteria interactions with Lactobacillus spp., which is largely understudied. Model predictions for composition changes after menses and antibiotics were not significantly different from those observed in clinical cohorts. Lastly, simulations were performed to illustrate how this quantitative framework can be used to gain insight into the development of new combinatorial therapies involving altered prebiotic and antibiotic dosing strategies. Altogether, dynamical models could guide development of more precise therapeutic strategies to manage BV.
format Online
Article
Text
id pubmed-10446192
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-104461922023-08-24 Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy Lee, Christina Y. Diegel, Jenna France, Michael T. Ravel, Jacques Arnold, Kelly B. PLoS Comput Biol Research Article The vaginal microbiome (VMB) is a complex microbial community that is closely tied to reproductive health. Optimal VMB communities have compositions that are commonly defined by the dominance of certain Lactobacillus spp. and can remain stable over time or transition to non-optimal states dominated by anaerobic bacteria and associated with bacterial vaginosis (BV). The ability to remain stable or undergo transitions suggests a system with either single (mono-stable) or multiple (multi-stable) equilibrium states, though factors that contribute to stability have been difficult to determine due to heterogeneity in microbial growth characteristics and inter-species interactions. Here, we use a computational model to determine whether differences in microbial growth and interaction parameters could alter equilibrium state accessibility and account for variability in community composition after menses and antibiotic therapies. Using a global uncertainty and sensitivity analysis that captures parameter sets sampled from a physiologically relevant range, model simulations predicted that 79.7% of microbial communities were mono-stable (gravitate to one composition type) and 20.3% were predicted to be multi-stable (can gravitate to more than one composition type, given external perturbations), which was not significantly different from observations in two clinical cohorts (HMP cohort, 75.2% and 24.8%; Gajer cohort, 78.1% and 21.9%, respectively). The model identified key microbial parameters that governed equilibrium state accessibility, such as the importance of non-optimal anaerobic bacteria interactions with Lactobacillus spp., which is largely understudied. Model predictions for composition changes after menses and antibiotics were not significantly different from those observed in clinical cohorts. Lastly, simulations were performed to illustrate how this quantitative framework can be used to gain insight into the development of new combinatorial therapies involving altered prebiotic and antibiotic dosing strategies. Altogether, dynamical models could guide development of more precise therapeutic strategies to manage BV. Public Library of Science 2023-08-11 /pmc/articles/PMC10446192/ /pubmed/37566641 http://dx.doi.org/10.1371/journal.pcbi.1011295 Text en © 2023 Lee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Christina Y.
Diegel, Jenna
France, Michael T.
Ravel, Jacques
Arnold, Kelly B.
Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
title Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
title_full Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
title_fullStr Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
title_full_unstemmed Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
title_short Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
title_sort evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10446192/
https://www.ncbi.nlm.nih.gov/pubmed/37566641
http://dx.doi.org/10.1371/journal.pcbi.1011295
work_keys_str_mv AT leechristinay evaluationofvaginalmicrobiomeequilibriumstatesidentifiesmicrobialparameterslinkedtoresilienceaftermensesandantibiotictherapy
AT diegeljenna evaluationofvaginalmicrobiomeequilibriumstatesidentifiesmicrobialparameterslinkedtoresilienceaftermensesandantibiotictherapy
AT francemichaelt evaluationofvaginalmicrobiomeequilibriumstatesidentifiesmicrobialparameterslinkedtoresilienceaftermensesandantibiotictherapy
AT raveljacques evaluationofvaginalmicrobiomeequilibriumstatesidentifiesmicrobialparameterslinkedtoresilienceaftermensesandantibiotictherapy
AT arnoldkellyb evaluationofvaginalmicrobiomeequilibriumstatesidentifiesmicrobialparameterslinkedtoresilienceaftermensesandantibiotictherapy