Another reason to breastfeed
Breast milk supports immune responses in newborns that help the infant's gut become a healthy home to a mix of necessary bacteria.
Scientists know at birth the gut is sterile and bacteria-free — then suddenly becomes exposed to bacteria initially via passage through the vaginal canal. Now, the body begins to build up its bacterial community in a mutually beneficial — commensal — relationship. In exchange for free meals, gut bacteria aid our own digestion, help prevent infection and enhance our immune function.
A healthy relationship between host and bacteria is called "commensal" — neither is harmed.
This newest study adds that breast milk also contributes antibodies. These antibodies interact with the infants' newly forming immune system to establish boundaries between them and the mammalian host — the baby. If this balance fails, or falters on occassion, chronic inflammatory conditions, such as Crohn's disease or ulcerative colitis, can result latter in the adult.
- In studies on mice, Gregory Barton PhD, Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley CA, USA, along with his post-doctoral fellow Meghan Koch, found three specific types of antibodies in breast milk:
(1) Immunoglobulin A (IgA)
(2) Immunoglobulin G2b (IgG2b)
(3) immunoglobulin G3 (IgG3)
These 3 antibodies promote peace between an infant's immune system and common gut bacteria by dampening all immune inflammatory responses.
"This study provides real evidence that breast milk is important for a newborn's health. Breastfeeding helps instruct the newborn's immune system on how to appropriately respond to non-pathogenic bacteria — many of which may reside in the gut for a lifetime."
Megan Koch PhD, post-doctoral fellow, University of California Berkeley, CA USA
The work was published in the May 5, 2016 issue of the journal Cell.
IgA antibodies in milk were already known, but thought mainly to fight pathogens, preventing them from entering the blood system through the gut.
IgG antibodies are known to enter the infant while in utero, to help fight infection. Scientists had previously identified sugars in breast milk (from which commensal bacteria get energy), which are indigestible to the infant. This phenomenon is evidence for a long, evolved relationship between mammals and gut microbes. Other molecules from mom's immune system are in breast milk to promote tolerance for commensal microbes, while keeping them away from the rest of the body.
IgG2b and IgG3 trigger immune responses against commensal bacteria in two-week-old mice — but diminish after three weeks, then grow stronger again in older mice. "The presence of these antibodies in young mice suggests, like IgA, they are all maternally derived," Koch explained. When she genetically eliminated maternally derived IgG2b, IgG3 and IgA antibodies, the mice were more susceptible to inflammatory responses caused by commensal microbes.
Barton found these distinctive immune responses by a newborn's immature immune system to be "surprising." Researchers saw that antibody responses against gut microbiota did not depend on exciting T helper cells — the foot soldiers of our advanced "adapted" immune system — but relied on signals from our earlier-evolved, innate immune system.
Barton suggests our immune responses might be setting up our immune system to identify and eliminate even commensal bacteria that escape through the gut to enter the blood, without triggering an overwhelming inflammatory response that might knock out even more bodily systems.
"We have learned that it is important for the immune system to recognize and make an immune response to microbiota in the gut — this response is qualitatively different than the immune response to pathogens.
"While our study demonstrates the importance of commensal-specific IgG antibodies acquired maternally, it is certainly possible they serve important functions in adults, as well."
Gregory Barton PhD, Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley CA, USA
Our characterization of anti-commensal IgG responses helps reconcile several observations regarding the function of antibodies in maintaining intestinal homeostasis. Despite the abundance of IgA within the gut, humans lacking this isotype display only subtle perturbations in intestinal immunity (Yel, 2010). In contrast, a proportion of human subjects with low levels of all circulating antibodies due to common variable immunodeficiency syndrome display pronounced intestinal defects including frequent gastrointestinal infections accompanied by a lymphoproliferative disorder of the small intestine (Washington et al., 1996). Some animals (e.g., cows, sheep, and horses) lack trans-placental transport of maternal antibodies. Notably, newborn calves fail to thrive without antibody-rich colostrum (Smith and Little, 1922), which, in light of our results, may be attributed to dysregulated immunity to commensal antigens in the absence of maternal antibodies.
This study expands our understanding of how appropriate mucosal immune responses are established following microbial colonization and reveals how immune dysregulation during development can influence intestinal homeostasis throughout life. The importance of maternal IgG has traditionally been ascribed to provision of passive immunity against a variety of pathogens, thereby protecting offspring from potentially fatal infections.
By demonstrating that mice deficient in maternal antibodies exhibit dysregulated mucosal responses, our data reveal a broader function for maternal IgG in helping to establish immune homeostasis early in life.
The work was supported by the National Institutes of Health (Grants AI063302, AI095587, AI104914). UC Berkeley co-authors of the paper include Gabrielle Reiner, Kyler Lugo, Lieselotte Kreuk, Alison Stanbery, Eduard Ansaldo, Thaddeus Seher and William Ludington.
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May 11, 2016 Fetal Timeline Maternal Timeline News News Archive
"Breastfeeding helps instruct the newborn's immune system on how to appropriately respond
to non-pathogenic bacteria — many of which may reside in the gut for a lifetime," Megan Koch.
Image Credit: public domain