By Sarah Anderson, PhD

Gold’s value lies in its unique properties, limited supply, and difficulty of extraction. The same is true of breastmilk — often touted as “liquid gold.” This precious commodity is comprised of a dynamic mixture of nutrients, hormones, growth factors, and antibodies tailored to support an infant’s health and development. 

Researchers in the lab of Brett Finlay, a professor at the Department of Microbiology and Immunology and the Michael Smith Laboratories at UBC, are studying how antibodies in breastmilk influence the bacteria present in the infant gut and how these bacteria in turn train the maturing immune system. Antibodies bind to different bacteria and help them attach to the gastrointestinal tract or carry them away, thereby shaping the members of a community of bacteria known as the gut microbiome. “Having a diverse gut microbiome and different bacteria exposure during the early life period is critical for the immune system to learn how to recognize and get rid of or support bacteria that are bad or good for the infant, respectively,” said Kate Donald, a recent PhD graduate of Finlay’s lab.

Donald’s work has focused on secretory immunoglobulin A (SIgA), the most prevalent antibody in breastmilk. Infants are not able to produce this antibody on their own and obtain it almost exclusively through breastmilk, which contains high quantities of the mother’s SIgA. In a 2024 Cell Reports study in mice, Donald and coauthors showed that maternal milk-derived SIgA blocked bacteria called segmented filamentous bacteria from occupying the gut, which reduced susceptibility to asthma.  

Now, in a recent PNAS study, Donald and her colleagues have uncovered similar relationships between antibodies in breastmilk, the infant gut microbiome, and immune development in humans. By identifying a key SIgA-targeted bacteria and discovering how it programs the immune response, this work unlocks new insight into how SIgA could protect against asthma, allergies, and other chronic diseases. “Scientifically, this is the jump from mouse model to humans we have all been looking for,” Finlay said.

To make this leap, the team leveraged the vast reserve of information gathered through the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study. At CHILD, researchers are following 3,500 Canadian children from pre-birth to adolescence, collecting data from biological samples, lifestyle and medical questionnaires, and clinical assessments. The CHILD researchers acquired stool samples from 3-month-old infants, which were analyzed with genetic sequencing tools to identify the species of bacteria present in their guts, and collected breastmilk samples from the infants’ mothers.

Honing in on a representative set of 300 mother-infant pairs, Donald used the genetic sequencing data to compile a list of bacterial species common to the infant gut microbiome and determine their abundance. She then quantified the SIgA in the breastmilk samples, defined its ability to bind to the different bacteria, and used a statistical model to compare the SIgA levels and binding capacity to the infant gut microbiome composition. Only one species, Erysipelatoclostridium ramosum, displayed a significant negative association with SIgA levels — that is, the more E. ramosum-binding SIgA in the milk, the less of the bacterium in the infant gut.

The researchers hypothesized that SIgA binds to E. ramosum and prevents it from inhabiting the infant gut. To find out, they cultured human cells derived from the intestinal lining and exposed them to E. ramosum bacteria they grew in the lab. They observed that E. ramosum attached to the cells, but that when they added breastmilk SIgA, the antibody bound to the bacteria and hindered its ability to adhere. 

To evaluate the consequences of these interactions on the immune system, the team analyzed changes in gene expression in the intestinal cells. They discovered that when E. ramosum attaches to the intestine, it activates signaling pathways that promote inflammation through T helper 17 (Th17) immune cells. When blocked by SIgA, however, the bacterium does not induce a Th17 immune response. The researchers further observed that a different bacterium that also adheres to the intestinal cells did not trigger a Th17 response. Together, these findings indicate that E. ramosum is equipped with a unique biological mechanism that activates the Th17 response, and that SIgA interferes with it. 

This is not the first time the team has encountered the Th17 immune response, which is implicated in asthma, allergies, and other inflammatory diseases. In their 2024 study in mice, they showed that segmented filamentous bacteria blooming in the gut contribute to asthma susceptibility by driving the Th17 response. Their latest findings suggest that this well-characterized mouse bacterium has a human equivalent in E. ramosum, which was recently identified as a core member of the infant gut microbiome and a primary allergy-associated microbe.  

To better understand the direct effect of E. ramosum on disease susceptibility, the researchers turned to the controlled environment of an animal model. However, the finicky bacterium seems to prefer interacting with human cells and did not grow in the mouse gut. Moving forward, researchers could attempt to gradually adapt E. ramosum to a mouse host in order to study its role in the development of asthma and allergies in vivo. Additionally, setting up a longitudinal study in humans specifically designed to investigate the relationships between E. ramosum levels in the infant gut microbiome, immune biomarkers, and disease outcomes would enable scientists to draw more rigorous conclusions. 

For now, the current evidence suggests that E. ramosum and SIgA could serve as promising therapeutic targets for promoting healthy immune development in infants. In order for a mother to have E. ramosum-binding antibodies in her blood and breastmilk, she must first have the bacterium in her gut. “E. ramosum might be a candidate for a maternal oral vaccine before or during pregnancy because if the mom has E. ramosum, she'll make SIgA against it and then give that SIgA to her infant through breastfeeding, which will protect them,” Donald said. 

Additionally, “Now that we have identified SIgA as a tool that modulates the infant gut microbiome, we could potentially use that to develop ways to improve the microbiome,” Finlay said. For example, in cases where breastfeeding is not possible, SIgA could be employed to enhance the health benefits of breastmilk alternatives. “Antibodies are pretty easy to synthesize; there are a lot of antibody therapies already out there,” Donald said. “So, adding that to formula to make it more like breastmilk could be a good future avenue.”