Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response

Denise Chan, Phillip R. Bennett, Yun S. Lee, Samit Kundu, T. G. Teoh, Malko Adan, Saqa Ahmed, Richard G. Brown, Anna L. David, Holly V. Lewis, Belen Gimeno-Molina, Jane E. Norman, Sarah J. Stock, Vasso Terzidou, Pascale Kropf, Marina Botto, David A. MacIntyre, Lynne Sykes*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

49 Scopus citations

Abstract

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

Original languageEnglish
Article number975
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - 12 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

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