Microbial, proteomic, and metabolomic profiling of the estrous cycle in wild house mice

Study information

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study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

38171017

DOI Digital object identifier for electronic documents.

https://doi.org/10.1128/spectrum.02037-23

URI

Authors

Matějková T, Dodoková A, Kreisinger J, Stopka P, Stopková R

Journal

Microbiology spectrum

Year

2024

Keywords:

16S RNA sequencing, Mus musculus, Pasteurellaceae, estrous cycle, estrus, microbiome, oral, proteome, saliva, vaginal

Symbiotic microbial communities affect the host immune system and produce molecules contributing to the odor of an individual. In many mammalian species, saliva and vaginal fluids are important sources of chemical signals that originate from bacterial metabolism and may act as honest signals of health and reproductive status. In this study, we aimed to define oral and vaginal microbiomes and their dynamics throughout the estrous cycle in wild house mice. In addition, we analyzed a subset of vaginal proteomes and metabolomes to detect potential interactions with microbiomes. 16S rRNA sequencing revealed that both saliva and vagina are dominated by Firmicutes and Proteobacteria but differ at the genus level. The oral microbiome is more stable during the estrous cycle and most abundant bacteria belong to the genera Gemella and Streptococcus, while the vaginal microbiome shows higher bacterial diversity and dynamics during the reproductive cycle and is characterized by the dominance of Muribacter and Rodentibacter. These two genera cover around 50% of the bacterial community during estrus. Proteomic profiling of vaginal fluids revealed specific protein patterns associated with different estrous phases. Highly expressed proteins in estrus involve the keratinization process thus providing estrus markers (e.g., Hrnr) while some proteins are downregulated such as immune-related proteins that limit bacterial growth (Camp, Clu, Elane, Lyz2, and Ngp). The vaginal metabolome contains volatile compounds potentially involved in chemical communication, for example, ketones, aldehydes, and esters of carboxylic acids. Data integration of all three OMICs data sets revealed high correlations, thus providing evidence that microbiomes, host proteomes, and metabolomes may interact.IMPORTANCEOur data revealed dynamic changes in vaginal, but not salivary, microbiome composition during the reproductive cycle of wild mice. With multiple OMICs platforms, we provide evidence that changes in microbiota in the vaginal environment are accompanied by changes in the proteomic and metabolomics profiles of the host. This study describes the natural microbiota of wild mice and may contribute to a better understanding of microbiome-host immune system interactions during the hormonal and cellular changes in the female reproductive tract. Moreover, analysis of volatiles in the vaginal fluid shows particular substances that can be involved in chemical communication and reproductive behavior.

Experiment 1

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incomplete

Curated date: 2024/03/18

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Subjects

Location of subjects

Czechia

Host species Species from which microbiome was sampled. Contact us to have more species added.

Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Vagina , Saliva Vagina,vagina,Distal oviductal region,Distal portion of oviduct,Vaginae,Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Fertilized ovule stage Fertilized ovule stage,fertilized ovule stage

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Oral (saliva)

Group 1 name Corresponds to the case (exposed) group for case-control studies

Vagina

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Oral and vaginal samples were noninvasively collected by gentle flushing with 2 × 30 µL of sterile dH2O on the day 21

Group 0 sample size Number of subjects in the control (unexposed) group

18

Group 1 sample size Number of subjects in the case (exposed) group

18

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

relative abundances

Statistical test

Random Forest Analysis

ANCOM

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

unchanged

Richness Number of species

increased

Signature 1

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Source: figure 1

Description: Graphical depiction of the relative abundance of dominant bacterial genera (Vagina Microbiome during the proestrus cycle)

Abundance in Group 1: increased abundance in Vagina

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Delftia
Lactobacillales
Staphylococcus

Revision editor(s): Omojokunoluwatomisin

Signature 2

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Source: Figure 1

Description: Graphical depiction of the relative abundance of dominant bacterial genera (Vagina Microbiome during the estrus cycle)

Abundance in Group 1: increased abundance in Vagina

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Lactobacillales
Rodentibacter
Streptococcus
unclassified Muribaculaceae

Revision editor(s): Omojokunoluwatomisin

Signature 3

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Source: Figure 1

Description: Graphical depiction of the relative abundance of dominant bacterial genera (Vagina Microbiome during the Metestrus cycle)

Abundance in Group 1: increased abundance in Vagina

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Corynebacterium
Delftia
Lactobacillales
Lactobacillus
Pseudomonas
Rodentibacter

Revision editor(s): Omojokunoluwatomisin

Signature 4

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Source: Figure 1

Description: Graphical depiction of the relative abundance of dominant bacterial genera (Vaginal microbiome in the diestrus cycle)

Abundance in Group 1: increased abundance in Vagina

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Delftia
Rodentibacter
Pseudomonas

Revision editor(s): Omojokunoluwatomisin

Signature 5

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Source: Figure 1

Description: Graphical depiction of the relative abundance of dominant bacterial genera in oral samples during different phases of the estrous cycle (P, E, M, D = proestrus, estrus, metestrus, diestrus).

Abundance in Group 1: decreased abundance in Vagina

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Gemella
Streptococcus

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Source: Figure 3a

Description: Significant differences in microbiota on the genus level between oral and vaginal samples. Relative average abundances of the most represented bacterial genera in oral and vaginal samples are graphically depicted in bar plot (A). Random Forest

Abundance in Group 1: increased abundance in Vagina

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Bergeyella
Cutibacterium
Delftia
Enterococcus
Lactobacillales
Phyllobacterium
Pseudomonas
Rodentibacter
Staphylococcus
Muribaculaceae

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Signature 7

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Source: Figure 3a

Description: Significant differences in microbiota on the genus level between oral and vaginal samples. Relative average abundances of the most represented bacterial genera in oral and vaginal samples are graphically depicted in bar plot (A). Random Forest

Abundance in Group 1: decreased abundance in Vagina

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Bradyrhizobium
Corynebacterium
Gemella
Lactobacillus
Methylobacterium
Streptococcus
unclassified Muribaculaceae

Revision editor(s): Omojokunoluwatomisin

Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Oral (saliva) sample

Group 1 name Corresponds to the case (exposed) group for case-control studies

Vagina sample

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

vagina sample collected

Lab analysis

Statistical Analysis

Statistical test

ANCOM

Random Forest Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)

0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

decreased

Richness Number of species

unchanged

Signature 1

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Source: Figure 5d

Description: Random Forest determined bacterial genera in oral (B) and vaginal (D) samples, which are important for the classification of data into four phases of the cycle.

Abundance in Group 1: increased abundance in Vagina sample

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Massilia
muribactermuribacter

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Source: Figure 5b

Description: Random Forest determined bacterial genera in oral (B) and vaginal (D) samples, which are important for the classification of data into four phases of the cycle.

Abundance in Group 1: decreased abundance in Vagina sample

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Gemella
Rodentibacter

Revision editor(s): Omojokunoluwatomisin