Complement in breast milk modifies offspring gut microbiota to promote infant health

Dongqing Xu, Siyu Zhou, Yue Liu, Alan Scott, Jian Yang, Fengyi Wan

Research output: Contribution to journalArticlepeer-review


Breastfeeding offers demonstrable benefits to newborns and infants by providing nourishment and immune protection and by shaping the gut commensal microbiota. Although it has been appreciated for decades that breast milk contains complement components, the physiological relevance of complement in breast milk remains undefined. Here, we demonstrate that weanling mice fostered by complement-deficient dams rapidly succumb when exposed to murine pathogen Citrobacter rodentium (CR), whereas pups fostered on complement-containing milk from wild-type dams can tolerate CR challenge. The complement components in breast milk were shown to directly lyse specific members of gram-positive gut commensal microbiota via a C1-dependent, antibody-independent mechanism, resulting in the deposition of the membrane attack complex and subsequent bacterial lysis. By selectively eliminating members of the commensal gut community, complement components from breast milk shape neonate and infant gut microbial composition to be protective against environmental pathogens such as CR.

Original languageEnglish (US)
Pages (from-to)750-763.e20
Issue number3
StatePublished - Feb 1 2024


  • Citrobacter rodentium
  • MAC deposition
  • Staphylococcus lentus
  • antibody-independent
  • infant health

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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