{{Short description|Protection provided to immune system via human milk}} [[File:A microscopy image of a sample of human breast milk.JPG|thumb|A microscopy image of a sample of human breast milk]] '''Human milk immunity''' is the protection provided to the [[immune system]] of an [[infant]] via the biologically active components in [[human milk]]. Human milk was previously thought to only provide [[passive immunity]] primarily through [[Secretory IgA]], but advances in technology have led to the identification of various immune-modulating components.<ref name=":1">{{cite journal | vauthors = Petherick A | title = Development: Mother's milk: A rich opportunity | journal = Nature | volume = 468 | issue = 7327 | pages = S5-7 | date = December 2010 | pmid = 21179083 | doi = 10.1038/468S5a | bibcode = 2010Natur.468S...5P | doi-access = free }}</ref><ref name=":2">{{Cite book|title=Breastfeeding New Anthropological Approaches|last=Miller|first=Elizabeth|publisher=Routledge|year=2018|isbn=978-1-138-50287-1|editor-last=Tomori|editor-first=Cecilia|editor-last2=Palmquist|editor-first2=Aunchalee E.L.|editor-last3=Quinn|editor-first3=EA | name-list-style = vanc |location=New York|pages=26–36|chapter=Beyond Passive Immunity Breastfeeding, milk and collaborative mother-infant immune systems}}</ref><ref name=":9">{{cite journal | vauthors = Garofalo R | title = Cytokines in human milk | journal = The Journal of Pediatrics | volume = 156 | issue = 2 Suppl | pages = S36-40 | date = February 2010 | pmid = 20105664 | doi = 10.1016/j.jpeds.2009.11.019 }}</ref> Human milk constituents provide nutrition and protect the immunologically naive infant as well as regulate the infant's own immune development and growth.<ref name=":13">{{cite book | last1=Martin |first1=MA |last2=Sela |first2=DA |chapter=Infant Gut Microbiota: Developmental Influences and Health Outcomes|year=2013|pages=233–256 | veditors = Clancy KB, Hinde K, Rutherford JN |publisher=Springer |location=New York | doi=10.1007/978-1-4614-4060-4_11|isbn=978-1-4614-4059-8 |title=Building Babies}}</ref>
Immune factors and immune-modulating components in human milk include [[cytokine]]s, [[Growth Factors (journal)|growth factors]], [[protein]]s, [[microbes]], and [[human milk oligosaccharide]]s.<ref>{{cite journal | vauthors = Collado MC, Cernada M, Baüerl C, Vento M, Pérez-Martínez G | title = Microbial ecology and host-microbiota interactions during early life stages | journal = Gut Microbes | volume = 3 | issue = 4 | pages = 352–65 | date = 2012-07-14 | pmid = 22743759 | pmc = 3463493 | doi = 10.4161/gmic.21215 }}</ref><ref>{{cite journal | vauthors = Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A | title = The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery | journal = The American Journal of Clinical Nutrition | volume = 96 | issue = 3 | pages = 544–51 | date = September 2012 | pmid = 22836031 | doi = 10.3945/ajcn.112.037382 | doi-access = free }}</ref> Immune factors in human milk are categorized mainly as [[anti-inflammatory]]<ref name=":2" /> primarily working without inducing inflammation or activating the [[complement system]].<ref name=":0">{{cite journal | vauthors = Palmeira P, Carneiro-Sampaio M | title = Immunology of breast milk | journal = Revista da Associação Médica Brasileira | volume = 62 | issue = 6 | pages = 584–593 | date = September 2016 | pmid = 27849237 | doi = 10.1590/1806-9282.62.06.584 | doi-access = free }}</ref> {{TOC limit}}
== Immune factors == Bio-active constituents of human milk that have been cataloged to possess immune-modulating capabilities include [[immunoglobulins]], [[Lactoferrin]], [[Lysozyme]], [[oligosaccharide]]s, [[lipid]]s, [[cytokine]]s, [[hormone]]s, and [[growth factor]]s.<ref name=":0" /><ref name=":3" /> Some of the roles of [[bio-active]]s in human milk are theorized based on their function in other parts of the body, but the mechanisms and function of their activities remain to be discovered.<ref name=":10" />
=== IgA === [[Immunoglobulin A]] is the most well known immune factor in human milk.<ref name=":2" /> In its secretory form, [[Secretory IgA|SIgA]], it is the most plentiful antibody in human milk.<ref name=":2" /><ref name=":3" /> It constitutes between 80 and 90% of all immunoglobulins present in milk.<ref name=":3" /> SIgA provides adaptive immunity by directly targeting specific pathogens that both the infant and the mother have been exposed to in their environments.<ref name=":2" /><ref name=":5">{{cite journal | vauthors = Weaver LT, Arthur HM, Bunn JE, Thomas JE | title = Human milk IgA concentrations during the first year of lactation | journal = Archives of Disease in Childhood | volume = 78 | issue = 3 | pages = 235–9 | date = March 1998 | pmid = 9613353 | pmc = 1717486 | doi = 10.1136/adc.78.3.235 }}</ref>
=== Lactoferrin === [[Lactoferrin]] is an immune protein with strong anti-microbial function in human milk.<ref name=":11" /> Lactoferrin protects the infant intestine by binding to iron to prevent pathogens from utilizing it as a resource. It also modulates immunity by blocking inflammatory signaling cytokines.<ref name=":0" />
=== Cytokines === [[Cytokine]]s are pluripotent signaling molecules with the ability to bind to specific receptors.<ref name=":9" /> They can cross the intestinal barrier and mediate immune activity.<ref name=":8" /> Their presence in human milk may stimulate lymphocytes responsible for the development of the infant's specific immunity.<ref name=":0" /> Cytokines present in human milk include [[Interleukin 1 beta|IL-1β]], IL-6, IL-8, IL-10, [[Tumor necrosis factor alpha|TNFα]], and [[Interferon gamma|IFN-γ]].<ref name=":9" />
== Origin and establishment == Bio-active components in human milk are speculated to colonize in human milk in several ways including secretion by the [[mammary gland]], [[epithelium]] cells, and by milk cells.<ref name=":9" /><ref name=":8" /> Maternal immune factors are transferred by [[lymphocyte]]s traveling from the mother's gut to the [[mammary gland]]<ref name=":3" /> where the [[secretory cell]]s of the breast produce [[antibodies]].<ref name=":5" />
The origin of the human milk microbiota, including those with immune-modulating functions, are not well established. However, several theories including [[skin-to-skin contact]],<ref name=":2" /> the entero-mammary pathway,<ref>{{cite journal | vauthors = Rodríguez JM | title = The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? | journal = Advances in Nutrition | volume = 5 | issue = 6 | pages = 779–84 | date = November 2014 | pmid = 25398740 | pmc = 4224214 | doi = 10.3945/an.114.007229 }}</ref> and retrograde back-flow hypothesis<ref>{{cite journal | vauthors = Ramsay DT, Kent JC, Owens RA, Hartmann PE | title = Ultrasound imaging of milk ejection in the breast of lactating women | journal = Pediatrics | volume = 113 | issue = 2 | pages = 361–7 | date = February 2004 | pmid = 14754950 | doi = 10.1542/peds.113.2.361 | url = https://pediatrics.aappublications.org/content/113/2/361 | url-access = subscription }}</ref><ref>{{cite journal | vauthors = Moossavi S, Sepehri S, Robertson B, Bode L, Goruk S, Field CJ, [[Lisa Lix|Lix LM]], de Souza RJ, Becker AB, Mandhane PJ, Turvey SE, Subbarao P, Moraes TJ, Lefebvre DL, Sears MR, Khafipour E, Azad MB | title = Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors | language = English | journal = Cell Host & Microbe | volume = 25 | issue = 2 | pages = 324–335.e4 | date = February 2019 | pmid = 30763539 | doi = 10.1016/j.chom.2019.01.011 | doi-access = free }}</ref> have been put forth to explain the microbial composition of human milk.
== Known factors of influence == [[File:From Colostrum to Breastmilk - 4241.jpg|thumb|From Colostrum to Breastmilk in days]]
=== Lactation stage === Human milk immune composition is known to change over the course of lactation.<ref name=":8">{{cite journal | vauthors = Ballard O, Morrow AL | title = Human milk composition: nutrients and bioactive factors | journal = Pediatric Clinics of North America | volume = 60 | issue = 1 | pages = 49–74 | date = February 2013 | pmid = 23178060 | pmc = 3586783 | doi = 10.1016/j.pcl.2012.10.002 }}</ref> Most notably, antibody levels are lower in mature milk than in [[colostrum]],<ref name=":0" /> with [[Secretory IgA|SIgA]] measuring at up to 12 grams per liter in colostrum and decreasing to 1 gram per liter in mature milk.<ref name=":3" /> Studies find time [[Postpartum period|postpartum]] to be most influential on the presence of immune factors, including growth factors<ref name=":6">{{cite journal | vauthors = Munblit D, Treneva M, Peroni DG, Colicino S, Chow L, Dissanayeke S, Abrol P, Sheth S, Pampura A, Boner AL, Geddes DT, Boyle RJ, Warner JO | title = Colostrum and Mature Human Milk of Women from London, Moscow, and Verona: Determinants of Immune Composition | journal = Nutrients | volume = 8 | issue = 11 | page = 695 | date = November 2016 | pmid = 27827874 | pmc = 5133082 | doi = 10.3390/nu8110695 | doi-access = free }}</ref> and lactoferrin.<ref name=":11">{{cite journal | vauthors = Rai D, Adelman AS, Zhuang W, Rai GP, Boettcher J, Lönnerdal B | title = Longitudinal changes in lactoferrin concentrations in human milk: a global systematic review | journal = Critical Reviews in Food Science and Nutrition | volume = 54 | issue = 12 | pages = 1539–47 | date = 2014-12-02 | pmid = 24580556 | doi = 10.1080/10408398.2011.642422 | s2cid = 5230921 }}</ref>
=== Human milk microbiome === The exposure to microbiota through mother's milk is the primary stimulus for immune development in infants.<ref name=":3">{{Cite book|title=Immunology of Human Milk: How Breastfeeding Protects Babies|last=Hanson|first=Lars A.|publisher=Pharmasoft Publishing|year=2004|isbn=978-0-9729583-0-1|location=Amarillo, Texas|pages=22}}</ref> Microbiota interacts with the infant's immune system by stimulating the mucous layer, down-regulating the inflammatory response, producing antibodies and helping initiate [[oral tolerance]].<ref name=":4">{{cite journal | vauthors = Houghteling PD, Walker WA | title = From Birth to "Immunohealth," Allergies and Enterocolitis | journal = Journal of Clinical Gastroenterology | volume = 49 Suppl 1 | issue = 1 | pages = S7–S12 | date = 2015 | pmid = 26447970 | pmc = 4602161 | doi = 10.1097/MCG.0000000000000355 }}</ref> Mucosal layers protection comes from their ability to limit pathogens from attaching to the infant [[Gastrointestinal tract|intestinal tract]].<ref name=":3" />
=== Human milk oligosaccharides === [[Human milk oligosaccharide]]s (HMOs) are carbohydrate components in human milk.<ref name=":8" /> They are mostly indigestible and work as a [[Prebiotic (nutrition)|prebiotic]] to feed [[Commensalism|commensal]] bacteria in the infant gut.<ref name=":10" /><ref>{{cite journal | vauthors = Davis EC, Wang M, Donovan SM | title = The role of early life nutrition in the establishment of gastrointestinal microbial composition and function | journal = Gut Microbes | volume = 8 | issue = 2 | pages = 143–171 | date = March 2017 | pmid = 28068209 | pmc = 5390825 | doi = 10.1080/19490976.2016.1278104 }}</ref> Studies show that HMOs also function as immune-modulators by blocking receptors that allow pathogenic bacteria to attach to the infant intestinal epithelium.<ref>{{cite journal | vauthors = Laucirica DR, Triantis V, Schoemaker R, Estes MK, Ramani S | title = Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells | journal = The Journal of Nutrition | volume = 147 | issue = 9 | pages = 1709–1714 | date = September 2017 | pmid = 28637685 | pmc = 5572490 | doi = 10.3945/jn.116.246090 }}</ref>
=== Delivery mode === There are observed differences in immune factor composition in the milk of mothers who delivered cesarean versus vaginally.<ref>{{cite journal | vauthors = Urbaniak C, Angelini M, Gloor GB, Reid G | title = Human milk microbiota profiles in relation to birthing method, gestation and infant gender | journal = Microbiome | volume = 4 | issue = 1 | article-number = 1 | date = January 2016 | pmid = 26739322 | pmc = 4702315 | doi = 10.1186/s40168-015-0145-y | doi-access = free }}</ref> A study of 82 women saw an increase in the levels of IgA in the colostrum of women who had cesarean births after experiencing labor when compared to women who delivered vaginally or had elected [[Caesarean section|cesareans]].<ref>{{cite journal | vauthors = Striker GA, Casanova LD, Nagao AT | title = [Influence of type of delivery on A, G and M immunoglobulin concentration in maternal colostrum] | journal = Jornal de Pediatria | volume = 80 | issue = 2 | pages = 123–8 | date = March 2004 | pmid = 15079182 | doi = 10.2223/1151 | doi-broken-date = 9 October 2025 | doi-access = free }}</ref>
=== Maternal Characteristics ===
==== Parity ==== [[Milk immunity]] levels are observably lower in women with higher [[Gravidity and parity|parity]].<ref name=":12">{{cite journal | vauthors = Prentice AM, Roberts SB, Prentice A, Paul AA, Watkinson M, Watkinson AA, Whitehead RG | title = Dietary supplementation of lactating Gambian women. I. Effect on breast-milk volume and quality | journal = Human Nutrition: Clinical Nutrition | volume = 37 | issue = 1 | pages = 53–64 | date = January 1983 | pmid = 6341320 }}</ref> A study among the [[Ariaal people|Ariaal]] women of Kenya saw that milk IgA decreased drastically only in women who had given birth to eight or more children.<ref name=":17">{{cite journal | vauthors = Miller EM, McConnell DS | title = Milk immunity and reproductive status among Ariaal women of northern Kenya | journal = Annals of Human Biology | volume = 42 | issue = 1 | pages = 76–83 | date = January 2015 | pmid = 25154290 | doi = 10.3109/03014460.2014.941398 | s2cid = 5417894 }}</ref>
==== Diet ==== Human milk composition remains relatively stable despite maternal dietary changes, except in cases of extreme maternal depletion. Seasonal changes and malnutrition influence the concentration of immune factors.<ref name=":12" />
In addition, intervention studies have confirmed that both fish oil<ref>{{cite journal | vauthors = Dunstan JA, Roper J, Mitoulas L, Hartmann PE, Simmer K, Prescott SL | title = The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition | journal = Clinical and Experimental Allergy | volume = 34 | issue = 8 | pages = 1237–42 | date = August 2004 | pmid = 15298564 | doi = 10.1111/j.1365-2222.2004.02028.x | s2cid = 929819 }}</ref> and fish consumption during pregnancy can alter immune-modulating components in human milk.<ref>{{cite journal | vauthors = Urwin HJ, Miles EA, Noakes PS, Kremmyda LS, Vlachava M, Diaper ND, Pérez-Cano FJ, Godfrey KM, Calder PC, Yaqoob P | title = Salmon consumption during pregnancy alters fatty acid composition and secretory IgA concentration in human breast milk | journal = The Journal of Nutrition | volume = 142 | issue = 8 | pages = 1603–10 | date = August 2012 | pmid = 22739373 | doi = 10.3945/jn.112.160804 | doi-access = free }}</ref>
=== Environmental factors === Differences in the maternal environment such as rural and urban environments,<ref name=":7" /> including exposure to farming,<ref>{{cite journal | vauthors = Peroni DG, Pescollderungg L, Piacentini GL, Rigotti E, Maselli M, Watschinger K, Piazza M, Pigozzi R, Boner AL | title = Immune regulatory cytokines in the milk of lactating women from farming and urban environments | journal = Pediatric Allergy and Immunology | volume = 21 | issue = 6 | pages = 977–82 | date = September 2010 | pmid = 20718928 | doi = 10.1111/j.1399-3038.2010.00995.x | s2cid = 22542754 }}</ref> and exposure to pathogens<ref>{{cite journal | vauthors = Tomicić S, Johansson G, Voor T, Björkstén B, Böttcher MF, Jenmalm MC | title = Breast milk cytokine and IgA composition differ in Estonian and Swedish mothers-relationship to microbial pressure and infant allergy | journal = Pediatric Research | volume = 68 | issue = 4 | pages = 330–4 | date = October 2010 | pmid = 20581738 | doi = 10.1203/00006450-201011001-00646 | doi-access = free }}</ref> have shown to affect human milk immune factor variation.<ref name=":2" />
=== Geographic location === Geographic location is known to play a role in human milk variation, with country of residence specifically linked with immune factor variation.<ref>{{cite journal | vauthors = Amoudruz P, Holmlund U, Schollin J, Sverremark-Ekström E, Montgomery SM | title = Maternal country of birth and previous pregnancies are associated with breast milk characteristics | journal = Pediatric Allergy and Immunology | volume = 20 | issue = 1 | pages = 19–29 | date = February 2009 | pmid = 18484963 | doi = 10.1111/j.1399-3038.2008.00754.x | doi-access = free }}</ref> A study found a variation in levels of growth factor in both mature milk and colostrum to be correlated with geographic location.<ref name=":6" /> However, a larger study found support for consistency in the presence of a small group of immunological factors in mature milk independent of geographic location.<ref name=":7">{{cite journal | vauthors = Ruiz L, Espinosa-Martos I, García-Carral C, Manzano S, McGuire MK, Meehan CL, McGuire MA, Williams JE, Foster J, Sellen DW, Kamau-Mbuthia EW, Kamundia EW, Mbugua S, Moore SE, Kvist LJ, Otoo GE, Lackey KA, Flores K, Pareja RG, Bode L, Rodríguez JM | title = What's Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings | language = English | journal = Frontiers in Immunology | volume = 8 | article-number = 696 | date = 2017 | pmid = 28713365 | pmc = 5492702 | doi = 10.3389/fimmu.2017.00696 | doi-access = free }}</ref>
== Impact on health ==
=== Health outcomes for Breastfed versus formula-fed infants === [[File:Nutramigen Baby Formula.JPG|thumb|Formula]] Over the last century, breastfeeding has been consistently shown to reduce infant mortality and morbidity, particularly of infectious disease.<ref name=":3" /> Comparative research between human milk and formula has pointed towards the bio-active components in human milk as potential proponents of its immunological protection.<ref name=":10">{{cite book | vauthors = Newburg DS | title = Bioactive Components of Human Milk | volume = 501 | pages = 3–10 | date = 2001 | pmid = 11787694 | doi = 10.1007/978-1-4615-1371-1_1 | publisher = Springer |location=US | isbn = 978-1-4615-1371-1 | series = Advances in Experimental Medicine and Biology }}</ref> Studies have shown that breastfed infants respond better to vaccines,<ref name=":18" /> and are better protected against [[diarrhea]], [[otitis media]], [[sepsis]], and [[necrotizing enterocolitis]],<ref name=":0" /> [[Celiac Disease|celiac disease]], [[obesity]], and [[inflammatory bowel disease]] than formula-fed infants.<ref name=":1" /> Human breast milk is seen as particularly beneficial to infants born before full term and those that are underweight at birth who are at a higher risk of infectious diseases, such as [[sepsis]] and [[meningitis]].<ref name=":0" /><ref name=":18" /> Also, there is a lower chance of contamination acquired through direct breastfeeding than with mixing formula with water or other animal milks which may also help explain why human milk is more protective for the infant.<ref>{{cite book | vauthors = Bernt K, Walker WA | title = Bioactive Components of Human Milk | chapter = Human Milk and the Response of Intestinal Epithelium to Infection | series = Advances in Experimental Medicine and Biology | volume = 501 | pages = 11–30 | date = 2001 | pmid = 11787672 | doi = 10.1007/978-1-4615-1371-1_2 | isbn = 978-1-4613-5521-2 }}</ref>
=== Long term protection === Because various components present in human breast milk stimulate the growth of the immune system, there is a growing interest in whether breastfeeding provides a long term protective effect against [[Autoimmunity|auto-immune]] and [[Inflammation|inflammatory diseases]].<ref name=":0" />
=== Milk sharing and donor milk === The [[World Health Organization|WHO]] infant feeding guidelines advise the use of donor milk when the mother's milk is not available.<ref name=":15">{{cite journal|vauthors=Palmquist AE, Doehler K|date=April 2016|title=Human milk sharing practices in the U.S|journal=Maternal & Child Nutrition|volume=12|issue=2|pages=278–90|doi=10.1111/mcn.12221|pmc=5063162|pmid=26607304}}</ref> With the understanding that breast milk provides immune protection that is absent in formula, mothers have turned to milk sharing options to in order to give formula alternatives to their infants.<ref name=":14">{{Cite web|url=http://milkgenomics.org/article/human-milk-sharing-evolutionary-insights-and-modern-risks/|title=Human Milk Sharing: Evolutionary Insights and Modern Risks|website=International Milk Genomics Consortium|language=en-US|access-date=2019-05-01}}</ref> A donation of milk without monetary benefit defines milk sharing.<ref name=":15" /> In addition, [[Human milk bank|milk banks]] have emerged to regulate and pasteurize donated milk to be sold in the legal market.<ref name=":14" /> The main concern with bank milk is that it has lost many immune cells, [[Commensalism|commensal]] [[microbiota]] and bio-active proteins during the [[pasteurization]] process.<ref>{{cite journal|vauthors=Martin CR, Ling PR, Blackburn GL|date=May 2016|title=Review of Infant Feeding: Key Features of Breast Milk and Infant Formula|journal=Nutrients|volume=8|issue=5|page=279|doi=10.3390/nu8050279|pmc=4882692|pmid=27187450|doi-access=free }}</ref> Donor milk is in high demand for infants in the Neonatal Intensive Care Unit ([[Neonatal intensive care unit|NICU]]).<ref name=":14" /> who have been shown to benefit most from access to human milk<ref>{{cite journal|vauthors=Schanler RJ, Lau C, Hurst NM, Smith EO|date=August 2005|title=Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants|journal=Pediatrics|volume=116|issue=2|pages=400–6|doi=10.1542/peds.2004-1974|pmid=16061595|s2cid=23798420 }}</ref>
Immunological consequences or benefits of milk sharing are not well documented, but it has been speculated that allo-nursing, or nursing from multiple females, may provide infants with an immune boost.<ref name=":14" /> The reported risk associated with unregulated sharing milk includes the possibility of the transmission of drugs, [[toxin]]s, [[pathogenic bacteria]], [[HIV]] and other [[virus]]es.<ref name=":14" /> However, some researchers believe that allo-nursing and milk sharing may have been part of our evolutionary past. Evidence of milk sharing history include the [[Wet nurse|wet nursing]] practices of the 20th century,<ref name=":14" /> [[milk kinship]] among Islamic tradition,<ref>{{Cite journal|last=Thorley|first=Virginia|date=2012|title=Mothers' experiences of sharing breastfeeding or breastmilk, part 2: the early 21st century|journal=Nursing Reports|volume=2|issue=1|article-number=e2|doi=10.4081/nursrep.2012.e2|issn=2039-4403|doi-access=free}}</ref> and documentation of allo-nursing in primates species.<ref name=":14" /><ref>{{Cite web|url=https://www.nationalgeographic.com/animals/2019/02/golden-snub-nosed-monkeys-nurse-others-babies/|archive-url=https://web.archive.org/web/20190223083553/https://www.nationalgeographic.com/animals/2019/02/golden-snub-nosed-monkeys-nurse-others-babies/|archive-date=February 23, 2019|title=Why do these monkeys nurse each other's babies?|date=2019-02-22|website=Animals|access-date=2019-05-01}}</ref>
==Evolutionary implications== There is evidence of a relationship between the microbes that have co-evolved with humans as their host and the human immune system.<ref>{{cite journal | vauthors = Hooper LV, Littman DR, Macpherson AJ | title = Interactions between the microbiota and the immune system | journal = Science | volume = 336 | issue = 6086 | pages = 1268–73 | date = June 2012 | pmid = 22674334 | pmc = 4420145 | doi = 10.1126/science.1223490 | bibcode = 2012Sci...336.1268H }}</ref> The transfer of microorganisms from mother to offspring is universal in animals. In humans, microbial exchange occurs primarily through placental transfer and breast milk.<ref>{{cite journal | vauthors = Funkhouser LJ, Bordenstein SR | title = Mom knows best: the universality of maternal microbial transmission | journal = PLOS Biology | volume = 11 | issue = 8 | article-number = e1001631 | date = 2013-08-20 | pmid = 23976878 | pmc = 3747981 | doi = 10.1371/journal.pbio.1001631 | doi-access = free }}</ref> The presence of these complex microbial communities in the human body suggests that the immune system has been selected to remember and mediate the colonization of these microorganisms within the human host.<ref>{{cite journal | vauthors = McFall-Ngai M | title = Adaptive immunity: care for the community | journal = Nature | volume = 445 | issue = 7124 | page = 153 | date = January 2007 | pmid = 17215830 | doi = 10.1038/445153a | bibcode = 2007Natur.445..153M | s2cid = 9273396 | doi-access = free }}</ref> Further, microbial [[dysbiosis]] in infants is strongly associated with immune-mediated diseases such as allergies and [[necrotizing enterocolitis]].<ref name=":4" />
In early life, an infant's immune system is considered immature due to its lack of resources necessary for defense against infection.<ref name=":0" /> An infant is not able to produce specific cytokines,<ref name=":18" /> IgA,<ref name=":0" /> and is limited to producing mostly IgM antibodies.<ref name=":18">{{Cite journal|last1=Hanson|first1=Lars Å.|last2=Korotkova|first2=Marina| name-list-style = vanc |date= August 2002 |title=The role of breastfeeding in prevention of neonatal infection|journal=Seminars in Neonatology | volume=7|issue=4|pages=275–281|doi=10.1053/siny.2002.0124|pmid=12401297 }}</ref> The human infant is unable to adequately protect itself without the immune-stimulating and immune-modulating components present in human milk. This dynamic affirms the consensus among researchers that human milk evolved to provide not only nutritional but immunological benefits to the infant.<ref name=":17" /> Some researches have proposed that the mammary gland and milk production evolved as a part of the human innate immune system,<ref>{{cite journal | vauthors = Vorbach C, Capecchi MR, Penninger JM | title = Evolution of the mammary gland from the innate immune system? | journal = BioEssays | volume = 28 | issue = 6 | pages = 606–16 | date = June 2006 | pmid = 16700061 | doi = 10.1002/bies.20423 }}</ref> with its immunological protective role predating its nutritional role.<ref>{{Cite journal|last1=Blackburn|first1=Daniel G.|last2=Hayssen|first2=Virginia|last3=Murphy|first3=Christopher J.| name-list-style = vanc |date=1989|title=The origins of lactation and the evolution of milk: a review with new hypotheses|journal=Mammal Review | volume=19|issue=1|pages=1–26|doi=10.1111/j.1365-2907.1989.tb00398.x|bibcode=1989MamRv..19....1B |s2cid=85913366 |issn=1365-2907}}</ref>
== See also == * [[Human milk microbiome]] * [[Human milk oligosaccharide]]
== References == {{Reflist}}
[[Category:Breastfeeding]] [[Category:Immunology]]