Nature Reviews Immunology ( IF 100.3 ) Pub Date : 2024-02-13 , DOI: 10.1038/s41577-024-01006-8 Maria Papatriantafyllou
Breast milk is known to contain antibodies and other immune mediators that provide immune protection and shape the gut microbiota. It also contains complement proteins — however, their physiological role was unclear. A study by Xu et al. shows that the complement components in mouse breast milk directly supports a ‘protective’ gut microbiota in the neonate intestine by selectively eliminating specific Gram-positive bacterial species. The authors found that pups fostered by complement-deficient dams suffered from intestinal inflammation, barrier damage and increased lethality upon challenge with the natural mouse gut pathogen Citrobacter rodentium. Further analyses of the microbiota linked C. rodentium pathogenicity with the composition of intestinal commensals and, specifically, with an increased presence of Gram-positive Staphylococcus lentus B3. Complement from both mouse and human breast milk was found to directly lyse S. lentus B3 via C1-initiated mechanisms that required the formation of membrane attack complex but was independent of antibodies.