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From Gut to Gland: How Intestinal Microbiota Induces the Secretion of Maternal Antibodies in Breastmilk

Does the gut microbiota affect the quality of breastmilk? Latest research has found a link between the mammary glands and the small intestine that plays an important role in transferring antibodies when breastfeeding.

During the first months of life, an infant is wholly dependent on their mothers and caregivers for food, hence the importance of breastmilk. As the ideal source of nutrition, breastmilk provides a near-perfect mix of vitamins, proteins, and fat, among many other factors needed to promote optimal health. Besides these basic necessities, breastmilk is also a crucial source of protection for infants as it contains antibodies that help the baby to combat viruses and bacteria, as well as lower the risks of developing asthma and allergies. However, the molecular mechanisms by which maternal antibodies, specifically immunoglobulin A (IgA), are produced in mothers during lactation still puzzle scientists.

Now, a group of researchers led by Tomonori Nochi from Tohoku University’s Graduate School of Agricultural Science has discovered that an interorgan network between the mammary glands and the small intestine plays an essential role in transferring maternal antibodies during breastfeeding.

According to Nochi, they embarked on this investigation in hopes of developing an immune strategy that can enhance the quality and quantity of maternal IgA in milk. He stated, “We still lack a complete picture when it comes to antibody production in lactating mothers, and this has hindered the discovery of immunological and microbiological approaches to increasing breastfeeding quality.”

The process of producing maternal IgA to infants first begins in the distinct intestinal tract. In the gut, resident microbes need to initiate an immune response in the gut-associated lymphoid tissue to induce the differentiation of immune cells into IgA plasma cells. The IgA plasma cells will then migrate into the mammary glands through chemokine signalling and locally produce secretory IgA.

While the process seems relatively comprehensive, it is still unclear how exactly specific lymphoid tissues in the gastrointestinal tract contribute to the production of maternal IgA in breastmilk. In particular, there is limited understanding with regards to how gut bacteria stimulate immune responses in the gastrointestinal tract to initiate the production of milk-borne IgA.

To address this gap, Nochi and colleagues sought to define the maternal gut-mammary axis. Their investigations led them to discover the unprecedented role of Peyer’s patches, immune sensors of the gastro-intestinal tract found throughout the ileum, in producing maternal IgA. The Peyer’s patches appeared to be the primary origin of plasma cells within the lactating mammary glands.

Using specially engineered mice that lack secondary lymphoid tissues – supramammary lymph nodes and Peyer’s patches – they analysed how the number of IgA plasma cells and secretory IgA levels in milk were affected. The results of their experiments strongly suggested that cells from the Peyer’s patches are recruited to the mammary glands to produce maternal IgA in breastmilk.

In addition, the scientists were also keen to investigate how the gut microbiome of mothers can affect the production of IgA in milk. By administering various antibiotics to female mice during pregnancy and lactation, the team examined how the antibiotic treatment altered the total bacterial count and how this affects the levels of IgA in milk. Their findings revealed that Bacteroides acidifaciens and Prevotella buccalis, which cohabitate the gastrointestinal tract of mothers, are major players in triggering immune responses in Peyer’s patches that are needed to induce the transfer of specific maternal IgA into milk.

With these new insights on the importance of the microbiota-Peyer’s patches-mammary gland pathway, the team hopes to refine present approaches to enhance lactational immunity and better understand the complex relationship between intestinal immunology and microbiology.

“Our results provide significant insights into the development of probiotics that facilitate the transfer of sufficient amounts of maternal antibodies from mother to the neonates via breastfeeding,” said Nochi. [APBN]

Source: Usami et al. (2021). The gut microbiota induces Peyer’s-patch-dependent secretion of maternal IgA into milk. Cell Reports, 36(10), 109655.