Comparative pangenomic analysis of predominant human vaginal lactobacilli strains towards population-specific adaptation: understanding the role in sustaining a balanced and healthy vaginal microenvironment
Open accessAbstract
The vaginal microenvironment of healthy women has a predominance of Lactobacillus crispatus, L. iners, L. gasseri , and L. jensenii . The genomic repertoire of the strains of each of the species associated with the key attributes thereby regulating a healthy vaginal environment needs a substantial understanding. We studied all available human strains of the four lactobacilli across different countries, isolated from vaginal and urinal sources through phylogenetic and pangenomic approaches. The findings showed that L. iners has the highest retention of core genes, and L. crispatus has more gene gain in the evolutionary stratum. Interestingly, L. gasseri and L. jensenii demonstrated major population-specific gene-cluster gain/loss associated with bacteriocin synthesis, iron chelating, adherence, zinc and ATP binding proteins, and hydrolase activity. Gene ontology enrichment analysis revealed that L. crispatus strains showed greater enrichment of functions related to plasma membrane integrity, biosurfactant, hydrogen peroxide synthesis, and iron sequestration as an ancestral derived core function, while bacteriocin and organic acid biosynthesis are strain-specific accessory enriched functions. L. jensenii showed greater enrichment of functions related to adherence, aggregation, and exopolysaccharide synthesis. Notably, the key functionalities are heterogeneously enriched in some specific strains of L. iners and L. gasseri . This study shed light on the genomic features and their variability that provides advantageous attributes to predominant vaginal Lactobacillus species maintaining vaginal homeostasis. These findings evoke the need to consider region-specific candidate strains of Lactobacillus to formulate prophylactic measures against vaginal dysbiosis for women’s health.
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Potential probiotic candidates for topical use should promote vaginal epithelial cell membrane integrity, adhere to the vaginal epithelium, and produce beneficial metabolites.
“potential probiotic candidates for topical use should show some key attributes, such as promoting vaginal epithelial cell membrane integrity, adhering to the vaginal epithelium, and producing beneficial metabolites [13].”
From Women's health is a team effort: probiogenomics supports the development of a multi-species vaginal probiotic (2026) · cites this paper as [13]
The Introduction (page unavailable) identifies adherence to vaginal epithelial cells as an important attribute of vaginal lactobacilli, and the Results (page unavailable) discuss synthesis of organic acids, hydrogen peroxide, and other potentially beneficial products. But the paper’s “plasma membrane integrity” refers to the bacteria’s own membranes, not promotion of vaginal epithelial cell membrane integrity. It also discusses vaginal probiotic candidates without specifying topical use. (LLM, conf=0.88)
Experimental — accuracy not yet measuredL. crispatus genome plasticity and ability to evolve may explain why this species is the most frequently found in the vaginal environment as dominant.
“Its genome plasticity and ability to evolve may explain why this species is the most frequently found in the vaginal environment as dominant [13].”
From Women's health is a team effort: probiogenomics supports the development of a multi-species vaginal probiotic (2026) · cites this paper as [13]
The Results (Pangenome profile and phylogeny; page unavailable) report that L. crispatus has the highest proportion of cloud genes among the four species studied, indicating gene gain and evolutionary diversification. The Introduction identifies it as one of four predominant vaginal lactobacilli, but the paper does not say it is the most frequently dominant species or link that frequency to its genomic plasticity. (LLM, conf=0.84)
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BackgroundInfluentialDraft Genome Sequence of Lactobacillus crispatus UMB1163, Isolated from the Female Urinary Tract
Khan, F., Miller-Ensminger, T., Voukadinova, A., Wolfe, A. J., & Putonti, C. (2020) · Microbiology Resource Announcements · doi:10.1128/mra.00404-20 · Cited by 3 · cited 1× · see citing works
“Among the four predominant vaginal Lactobacillus species, the genome size is largest in L. crispatus (2.03 Mb) [31, 32] and smallest in L. iners (1.36 Mb) [33], while L. gasseri (1.87 Mb) and L. jensenii (1.59 Mb) have intermediate genome sizes.”
BackgroundInfluential
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2 of the 61 references couldn’t be matched to a known paper.
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Vaginal dysbiosis and the potential of vaginal microbiome-directed therapeutics
Valeriano, V. D., Lahtinen, E., Hwang, I., Zhang, Y., Du, J., & Schuppe‐Koistinen, I. (2024) · Frontiers in Microbiomes · doi:10.3389/frmbi.2024.1363089 · Cited by 47 · see citing works
Nori, S. R. C., Walsh, C. J., McAuliffe, F. M., Moore, R. L., Van Sinderen, D., Feehily, C., & Cotter, P. D. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00682-1 · Cited by 29 · see citing works
Cheng, Q., Lv, S., Yin, N., & Wang, J. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00839-y · Cited by 31 · see citing works
Dubé‐Zinatelli, E., Cappelletti, L., & Ismail, N. (2024) · American Journal of Reproductive Immunology · doi:10.1111/aji.70026 · Cited by 22 · see citing works
Interconnected microbiomes—insights and innovations in female urogenital health
Al, K. F., Parris, J., Engelbrecht, K. C., Reid, G., & Burton, J. P. (2024) · FEBS Journal · doi:10.1111/febs.17235 · Cited by 19 · see citing works
“Adherence, acidification, bacteriocin, and antimicrobial compound production are thought to be among the key factors enabling lactobacilli colonization and pathogen exclusion, though these functionalities vary across species [33 – 35](Fig.”
Jiang, X., Bao, Y., Li, X., Qu, X., Mao, X., Dong, J., Wang, L., Liu, X., Zhang, F., & Hao, Y. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06460-z · Cited by 13 · see citing works
“This genetic adaptability might contribute to survival in diverse vaginal environments [42].”
Achudhan, A. B., & Saleena, L. M. (2024) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-024-04174-w · Cited by 5 · see citing works
“The pattern of a high proportion of cloud genes (72.74% to 88.71%), indicates a wide range of genetic variations and evolutionary divergence (Reis and Cunha 2021; Bhattacharya et al. 2023).”
InfluentialCalvanese, C. M., Valentino, V., De Prisco, A., Allesina, S., Amoruso, A., Deidda, F., Visciglia, A., Ercolini, D., Pane, M., & De Filippis, F. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06107-2 · Cited by 2 · see citing works
“GOs terms of interest for vaginal lactobacilli were considered as described in the supplementary material of the work by Bhattacharya et al. [13].”
InfluentialDubin, C. A., Zhao, C., Pollard, K. S., Oskotsky, T., Golob, J. L., & Sirota, M. (2026) · mSystems · doi:10.1128/msystems.01498-25
“L. crispatus vaginal isolates vary in their ability to utilize glycogen sources, produce hydrogen peroxide, and survive acidic stress (15).”
Wilson, J., Hamzah, A. S. A., Jordan, C. K. I., Hayward, J. A., Kullin, B., Manhanzva, M. T., Tyssen, D. P., Mehou‐Loko, C., Abrahams, A. G., Radzey, N., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.26.714511
Kumar, V., Kumari, S., Kumar, A., Patel, P., & Kurmi, B. D. (2026) · Nano Trends · doi:10.1016/j.nwnano.2026.100210
Longitudinal omics study of transcriptional dynamics in Lactobacillus crispatus
Ren, S., Jiang, H., Liu, X., Zhou, D., Liu, L., Wang, L., Lan, Y., Xiao, Y., & Tang, L. (2026) · PLoS ONE · doi:10.1371/journal.pone.0354930
“…and non-L. crispatus species indicate that the Lactobacillus genus is not a functionally homogeneous group, and the functional heterogeneity among different species may be an important reason explaining why L. crispatus is often associated with a more stable and protective vaginal ecosystem [32].”
He, Y., Zhao, Y., Ju, S., Zhou, P., Si, J., Pan, Y., & Jiang, Y. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1890330
Huang, Q., Zhang, L. Y., Shu, H. L., Chen, N., Li, R. H., Jiang, F., Li, G., Pu, M., Zhang, Q., Gao, Y. L., et al. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1891111
Wilson, J., Hamzah, A. S. A., Jordan, C. K. I., Hayward, J. A., Kullin, B., Manhanzva, M. T., Tyssen, D. P., Mehou‐Loko, C., Abrahams, A. G., Radzey, N., et al. (2026) · Applied and Environmental Microbiology · doi:10.1128/aem.00566-26
Vaginal Probiotic Potential of Lactobacillus acidophilus: Population Genomic and Phenotypic Analysis
Mao, Y., Che, Y., Li, M., Yan, G., Liu, X., Yang, R., Li, H., Fan, Y., Zhan, H., Sun, Z., et al. (2026) · Genes · doi:10.3390/genes17091009
“This core genome proportion is higher than the reported proportions for Lactobacillus iners , Lb. jensenii , Lb. crispatus , and Lb. gasseri (46.81%, 15.62%, 13.2%, and 9.83%, respectively) [45].”
Influential
- Authors
- Bhattacharya, A., Das, S., Bhattacharjee, M. J., Mukherjee, A. K., & Khan, M. R.
- Affiliations
- Institute of Advanced Study in Science and Technology (IN)
- Gauhati University (IN)
- Corresponding author
- Bhattacharjee, Maloyjo Joyraj
- Khan, Mojibur Rohman
- ORCID
- Venue
- BMC Genomics
- Published
- 2023-09-22
- Volume
- 24
- Issue
- 1
- Pages
- 565-565
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC10517566
- OpenAlex
- W4386958436
- Cited by
- 16
- References
- 61
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 4
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Department of Science and Technology, Ministry of Science and Technology, India (SEED/TITE/2019/103)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- vaginal lactobacilli, Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri, Lactobacillus jensenii, pan-genome, core genome, gene gain and loss, iron chelation, bacterial adhesion, exopolysaccharide biosynthesis, vaginal microbiota, vaginal dysbiosis
- MeSH terms
- Bacteriocins, Cell Membrane, Biological Evolution, Female, Humans, Lactobacillus, Phylogeny
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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