Megasphaera

Megasphaera is a genus of obligate anaerobic, Gram-negative bacteria in the family Veillonellaceae (class Negativicutes, phylum Firmicutes). The genus occupies two distinct ecological niches — the vaginal microbiome (where it is a hallmark of bacterial vaginosis) and the gut microbiome (where it functions as a beneficial SCFA producer). This dual role makes Megasphaera one of the most context-dependent organisms in the WikiBiome knowledge graph.

Vaginal Microbiome — BV Association

Megasphaera is one of the BV-associated bacteria (BVAB) consistently enriched when Lactobacillus-dominant vaginal communities shift toward dysbiosis:

  • Part of the Gardnerella-Atopobium-Megasphaera-Prevotella-Sneathia consortium that characterizes bacterial vaginosis and Community State Type IV (CST-IV) vaginal microbiomes.
  • Enriched in HPV16-positive cervical microbiomes alongside Sneathia, Prevotella, and Atopobium [1].
  • Associated with preterm birth risk when elevated in vaginal samples [2].

Endometriosis — Cervical Depletion

Counterintuitively, Megasphaera is depleted (not enriched) in cervical samples from endometriosis patients, alongside Gardnerella, Atopobium, and Prevotella, while Escherichia/Shigella and Dialister increased [3] [4] [5]. This suggests the endometriosis cervical microbiome is not simply "more dysbiotic" but represents a distinct ecological shift away from the BV-associated community.

  • Vaginal microecological characteristics in endometriosis show reduced Megasphaera compared to controls [6] [7].

Gut Microbiome — SCFA Producer

In the gut, Megasphaera plays a different role as a butyrate and propionate producer:

  • M. elsdenii is one of the most efficient lactate-utilizing organisms in the gut, converting lactate to butyrate and propionate via the acrylate pathway.
  • Enriched in ASD gut microbiota in some studies [8].
  • Altered in premenstrual disorders [9].
  • Depleted in Graves' disease gut microbiota [10].
  • Altered in postpartum depression [11].

The Context-Dependence Problem

Megasphaera illustrates why genus-level classification as "beneficial" or "pathogenic" fails:

NicheRoleImplication
Vagina (Lactobacillus-depleted)BV-associated pathobiontDrives inflammatory cascade, preterm birth risk
Vagina (endometriosis)DepletedLoss is part of endometriosis-specific cervical shift
Gut (healthy)Lactate-utilizing butyrate producerContributes to SCFA pool and barrier integrity
Gut (ASD)EnrichedPossibly compensatory overgrowth; unclear if cause or effect

Site-specific and disease-specific context determines whether Megasphaera presence is protective, pathological, or incidental.

Cross-References

References (13)

  1. Qian Yang, Yaping Wang, Xinyi Wei et al. (2020). Yang 2020 — Vaginal Microbiome Alterations in HPV16 Infection by Shotgun Metagenomics. Frontiers in Cellular and Infection Microbiology. doi:10.3389/fcimb.2020.00286
  2. Pamela Pruski, Gonçalo D. S. Correia, Holly V. Lewis et al. (2021). Pruski & Correia 2021 — Direct On-Swab Metabolic Profiling of Vaginal Microbiome Host Interactions During Pregnancy and Preterm Birth. Nature Communications. doi:10.1038/s41467-021-26215-w
  3. Baris Ata, Sule Yildiz, Engin Turkgeldi et al. (2019). Ata 2019 — The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy Controls. Scientific Reports. doi:10.1038/s41598-019-39700-6
  4. Chloe Hicks, Mathew Leonardi, Xin-Yi Chua et al. (2025). Hicks et al. 2025 — Oral, Vaginal, and Stool Microbial Signatures in Patients With Endometriosis as Potential Diagnostic Non-Invasive Biomarkers. BJOG: An International Journal of Obstetrics and Gynaecology. doi:10.1111/1471-0528.17979
  5. Hooi-Leng Ser, Siu-Jung Au Yong, Mohamad Nasir Shafiee et al. (2023). Ser 2023 — Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review. Microorganisms. doi:10.3390/microorganisms11020360
  6. Liping Shen, Wei Zhang, Yi Yuan et al. (2022). Shen 2022 — Vaginal Microecological Characteristics of Women in Different Physiological and Pathological Periods. Frontiers in Cellular and Infection Microbiology. doi:10.3389/fcimb.2022.959793
  7. Carlos H Miyashira, Fernanda Reali Oliveira, Marina Paula Andres et al. (2022). Miyashira 2022 — The Microbiome and Endometriosis. Reproduction and Fertility. doi:10.1530/RAF-21-0113
  8. Simeng Liu, Enyao Li, Zhenyu Sun et al. (2019). Liu 2019 — Altered Gut Microbiota and Short Chain Fatty Acids in Chinese Children with Autism Spectrum Disorder. Scientific Reports. doi:10.1038/s41598-018-36430-z
  9. Takashi Takeda, Kana Yoshimi, Sayaka Kai et al. (2022). Takeda 2022 — Gut Microbiota in Women with Premenstrual Symptoms. PLOS ONE. doi:10.1371/journal.pone.0268466
  10. Su X, Yin X, Liu Y et al. (2020). Alteration in gut microbiota is associated with immune imbalance in Graves' disease. EBioMedicine. doi:10.1016/j.ebiom.2020.102952
  11. Yumei Zhou, Chen Chen, Haibo Yu et al. (2020). Zhou 2020 — Fecal Microbiota Changes in Patients With Postpartum Depressive Disorder. Frontiers in Cellular and Infection Microbiology. doi:10.3389/fcimb.2020.567268
  12. Chen H, Wang L, Zhao L et al. (2021). Chen 2021 — Alterations of vaginal microbiota in women with infertility and Chlamydia trachomatis infection. Frontiers in Cellular and Infection Microbiology. doi:10.3389/fcimb.2021.698840
  13. Si Xian Ho, Jia-Hao Law, Chin-Wen Png et al. (2024). Alterations in colorectal cancer virome and its persistence after surgery. Scientific Reports. doi:10.1038/s41598-024-53041-z

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