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Gut Microbiome-targeting IgG Antibodies in Maternal Milk Protect Newborn Mice

    igg protects infants maternal milk

    Written by: Jyoti Madhusoodanan, Ph.D. | Issue # 112 | 2023

    • IgG antibodies against commensal gut bacteria are present in mother’s milk and help newborns combat infections.
    • Boosting levels of IgG antibodies in breastmilk confers additional protection to offspring.
    • A study in mice suggests that the transfer of IgG antibodies in milk is even more important than transfer via the placenta.
    • Future studies could lead to new ways to reduce infant mortality from gastrointestinal diseases such as diarrhea.

    Maternal milk is a potent cocktail of food and medicine: in addition to nutrients such as sugars and fats, it also carries antibodies that protect infants from various infections.

    Some of those antibodies target members of the gut microbiome. These bacteria are harmless and even beneficial, but—if unleashed into the bloodstream—can cause serious infections. Immunologist Melody Zeng of Weill Cornell Medicine in New York was one of the first researchers to discover that healthy animals carry antibodies belonging to the IgG class to protect against such disease [1]. In a new study, Zeng and her colleagues report that these antibodies are also transferred via maternal milk to newborn mice and play an important role in the developing gut microbiome of neonates [2]. “We knew the gut microbiome can induce IgG antibodies,” Zeng said in an interview. “But we didn’t know they could be protective in newborns.”

    Healthy adult animals typically develop these protective IgG antibodies when intestinal infections such as in food poisoning damage the intestinal lining and allow gut bacterial antigens to slip into the bloodstream. Newborn animals lack these exposures and thus need rotective antibodies.

    Zeng and her team began the new study by genetically engineering mice so that they lacked a cell surface protein named FcRn that transports IgG antibodies from mother to offspring.

    The researchers infected 18-day-old mice with a pathogen named Citrobacter rodentium, which causes an infection that mimics human infections caused by pathogenic strains of E. coli. About a week later, they found lower amounts of bacteria in control animals that had the FcRn protein. But the pathogen was still abundant in the engineered mice that didn’t receive maternal IgG antibodies because they lacked the FcRn protein. Two weeks after infection, all the mutant mice died, in contrast to almost complete protection in the IgG-rich control animals, the authors wrote in their paper.

    IgG antibodies are passed down from mother to offspring in two ways: by transfer across the placenta before birth and through ingestion of maternal milk after birth. To confirm that the effects they were seeing were due to maternal milk—and not antibodies received in the womb—the team cross-fostered newborn pups. Mice born to control animals were placed with mothers lacking the FcRn gene and vice versa. This way, engineered pups that had not received IgG antibodies in utero were placed with mothers that provided them the antibodies in milk. On the other hand, pups that received antibodies via the placenta would no longer get them in maternal milk.

    When the researchers infected the newborns with the same pathogen, all the engineered pups nursed by wild type animals survived the infection, but 70% of wild-type animals that were not receiving protective IgG antibodies in milk succumbed to the infection. The data suggest that IgG transfer after birth “accounts for most of the immune protection” against intestinal bacteria in newborns, the authors stated. The data reveal that supplying IgG antibodies to newborns through maternal milk can protect them against enteric infections.

    The team also found that immunizing female mice with a common bacterial protein increased the protective effects of maternal milk. When pups were infected with a high dose of C. rodentium, all the animals nursed by non-immunized mothers died compared with only ~20 percent of those with immunized mothers.

    Gastrointestinal infections among adult humans can cause mild or severe illness, but such infections are a leading cause of mortality among infants globally and pose a greater threat to infants born preterm [3]. Finding ways to boost immunity so as to reduce the risk of enteric infections among newborns could help address this problem, Zeng said in an interview. If further studies establish that these protective antibodies work in a similar way in humans, researchers could use that “to further protect newborns, especially those at risk of bacterial infections or sepsis,” she added.

     

    References

    1. Caballero-Flores G, Sakamoto K, Zeng MY, Wang Y, Hakim J, Matus-Acuña V, Inohara N, Núñez G. Maternal immunization confers protection to the offspring against an attaching and effacing pathogen through delivery of IgG in breast milk. Cell Host & Microbe. 2019 Feb 13;25(2):313-23.
    2. Sanidad KZ, Amir M, Ananthanarayanan A, Singaraju A, Shiland NB, Hong HS, Kamada N, Inohara N, Núñez G, Zeng MY. Maternal gut microbiome–induced IgG regulates neonatal gut microbiome and immunity. Science Immunology. 2022 Jun 10;7(72):eabh3816.
    3. Liu L, Hill K, Oza S, Hogan D, Chu Y, Cousens S, Mathers C, Stanton C, Lawn J, Black RE. Levels and causes of mortality under age five years. Reproductive, Maternal, Newborn, and Child Health. 2016 May 27;11:71.