IgG: Researchers have known for some time that breast milk provides essential nutrients to newborns, and antibodies from mothers who have been vaccinated against a specific disease-causing bacteria or virus can pass through breast milk to babies.
A new preclinical study by Weill Cornell Medicine investigators shows that a specific set of antibodies that are naturally stimulated by beneficial bacteria in the gut can be transferred from mothers to infants through breast milk and help infants defend against diarrheal illness caused by infection.
The study suggests that boosting these "natural" antibodies in mothers may enhance children's immunity against the bacterial pathogens that cause infectious gastrointestinal diseases.
In the study, published June 10 in Science Immunology, the team focused on a class of antibodies called IgG, which help the body rid the body of infectious bacteria and viruses. Little is known about how IgG antibodies that are naturally stimulated by gut bacteria affect the gut immunity of infants.
Therefore, the researchers used a mouse model to determine how IgG antibodies are transferred from the mother's blood into breast milk, and how they protect young mice from Citrobacter rodentium (the equivalent of pathogenic Escherichia coli in humans) that causes serious intestinal infections.
Melody Zeng, MD, associate professor of pediatric immunology in the Department of Pediatrics and a member of the Gill Institute and Ira Drucker Pediatric Research Institute at Weill Cornell Medicine, said.
Just as antibodies against SARS-CoV-2 were detected in the breast milk of women vaccinated with mRNA vaccines for COVID-19, researchers sought to provide additional protection against intestinal infections in infants by stimulating IgG antibodies that could be. this way. They developed a vaccine using an ingredient found in gut bacteria and then immunized female mice with it before conception.
"The same concept, in which vaccination boosts the mother's IgG antibody levels and transmits that immunity to her babies, can protect babies from humans," said Dr. Zeng. "This strategy could particularly benefit premature babies, as they tend to be at higher risk for diarrheal disease."
Such infections pose significant risks to young children in general. Diarrheal diseases are the second leading cause of death in children under five, according to the World Health Organization.
In their experiments, the researchers, including first authors Dr. Catherine Sendad and Dr. Muhammad Amir, both postdoctoral fellows in Zeng's lab, first showed that when passed to nursing mice via breast milk, IgG prevented pathogenic bacteria from attaching themselves to the lining of the breast. The intestines of infants, which is an early step in infection.
They also studied how IgG interacts with another group of microbes - the beneficial bacteria that live in the gut - to facilitate the healthy development of infants' gut bacteria. Scientists have found that these microbes contribute to the development and function of the immune system. For example, beneficial bacteria train the immune system to recognize their disease-causing relatives.
This study revealed the long-term effects of these protective IgG antibodies as well. Mice that never received IgG from their mothers developed abnormal microbial communities within their guts, which led to changes in their immune systems.
Specifically, the researchers found an increase in gut immune cells that produce IL-17, an anti-inflammatory cytokine linked to inflammatory diseases. As adults, mice deprived of IgG were more susceptible to the abnormal inflammation associated with inflammatory bowel disorder.
"Our findings really confirm the benefits of breastfeeding, both immediately and for the long-term development of the immune system in the offspring," said Dr. Zeng.
Dr. Melody Zeng is a consultant at Guide Point.
Katherine Z. Sanidad, Mohammed Amir, Aparna Ananthanarayanan, Anvita Singaraju, Nicholas B. Shiland, Hanna S. Hong, Nobuhiko Kamada, Naohiro Inohara, Gabriel Núñez, Melody Y. Zeng. The maternal gut microbiome–induced IgG regulates neonatal gut microbiome and immunity. Science Immunology, 2022; 7 (72) DOI: 10.1126/sciimmunol.abh3816