Antibodies from maternal microbiota could protect newborns from infection

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It is well-known that breastfeeding protects a newborn baby from potentially lethal infections. Now new research using murine models suggests that maternal antibodies produced in response to the intestinal microbiota could be a source of this immunity, protecting new-born pups against E. coli infections.

“Our results help explain why newborns are protected from certain disease-causing microbes, despite their underdeveloped immune systems and lack of prior encounters with these microbes,” explained author Dennis Kasper (Harvard Medical School, MA, USA).

“Moreover, they raise the possibility that mothers can confer immune protection to their offspring, even to pathogens that they haven’t themselves encountered in the past.”

In this study, the researchers used mice genetically engineered to lack antibody-producing B cells. Pups that lacked B cells were raised by mothers, both with and without this genetic alteration. Interestingly, mice reared to mothers with normal antibody-producing B cells were more resistant to E. coli infection and demonstrated an intestinal E. coli count 33-times lower than pups reared to mothers without antibody-producing B cells.

Further investigation led the team to identify Pantoea – an opportunistic pathogen in the Enterobacteriaceae family, commonly found in mammalian intestines – as the bacteria responsible for eliciting the protective antibodies.

The researchers also demonstrated that the neonatal Fc receptor allows the transportation of these antibodies across the placenta into the newborn’s intestines and the bloodstream. In addition, the team demonstrated this receptor could also absorb antibodies derived from milk, transporting these from the intestines into the bloodstream of newborn mice. This, therefore, provides systemic protection.

In older mice, when the Fc receptor has reduced in function, the team determined that the antibodies in the milk were not transferred into the bloodstream. Thus, highlighting the importance of the Fc receptor in the neonatal gut.

“Albeit preliminary, we are hopeful these insights could inform the development of vaccines derived from commensal microbial molecules as a way to prevent infectious diseases,” stated Kasper.

“Another therapeutic avenue could be the use of commensal microbes as probiotics that protect against diarrheal disease,” concluded Kasper.

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Sources: Zheng W, Zhao W, Wu M et al. Microbiota-targeted maternal antibodies protect neonates from enteric infection. Nature doi:10.1038/s41586-019-1898-4 (2020); https://hms.harvard.edu/news/mothers-bugs

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