Breast milk from rhinos and dolphins and whales, oh my!

A recent study has uncovered that the components of breast milk from land and sea mammals possess immunomodulatory components that may promote healthy microbiome colonization in offspring. These findings could inform efforts to develop better formula for human and animal infants.

Jin et al., Molecular & Cellular Proteomics (2023)

The Bojar lab used mass spectrometry to identify novel milk sugars in understudied mammals, like rhinos and sheep, that have immunomodulatory properties. This is the graphical abstract for their paper titled "Breast milk oligosaccharides contain immunomodulatory glucuronic acid and LacdiNAc."

The American Academy of Pediatrics and the World Health Organization recommend that mothers exclusively breastfeed their babies for the first six months of life, because it promotes infant survival and a healthy immune system. However, less than 30% of infants are breastfed, due to a variety of reasons such as maternal health and lack of support and resources. Therefore, there is a need to develop formula that more accurately mimics breast milk to promote the health of future generations.

According to Daniel Bojar, an assistant professor of chemistry and molecular biology at the University of Gothenburg in Sweden, scientists need to know more about nonhuman breast milk. Bojar oversaw the new study, which was published in the journal Molecular & Cellular Proteomics.

“For nearly all mammals, we have shallow or zero knowledge about what makes up their breast milk sugars,” Bojar said. “Knowledge from these species can shed light on human milk and therapeutic opportunities. Ultimately, this story is about the amazing things that nature has created and how we are just beginning to unlock their secrets. It's a tale of discovery, of nature's wonders and of the universal bond between mothers and their children.”

Bojar and colleagues examined breast milk from nine understudied mammal species: alpaca, beluga whale, black rhinoceros, bottlenose dolphin, impala, L'Hoest's monkey, pygmy hippopotamus, domestic sheep and striped dolphin. They found that the collective mammalian breast milk contained more than 100 novel milk sugars, including glucuronic acid, and these sugars were shared across species. According to Bojar, glucuronic acid is also found in cartilage and connective tissues.

Jin et al., Molecular & Cellular Proteomics (2023)

Shared milk oligosaccharides by taxonomic order. A pie chart with the proportion of milk glycans from various mammalian orders is shown, with rare orders being grouped under “Misc.”

After identifying these new milk sugars, Bojar’s team wanted to know what purpose they serve. The team exposed macrophages, an immune cell responsible for ingesting foreign invaders, to glucuronic acid-containing milk sugars and observed how it influenced the macrophage behavior and activation. Glucuronic acid dampened macrophages’ inflammatory response to bacteria, indicating that this milk sugar could help prevent excessive immune activation, common in autoimmune diseases, and promote healthy microbiome development in infants.

“We showed that these special sugars are advisers that help the baby's immune system make better decisions,” Bojar said. “In particular, these new molecules seem to aid in the development of the infant microbiome by allowing the good kind of bacteria to colonize the infant gut.”

Bojar said his team’s future work will focus on further dissecting the novel milk sugars found in these mammals and others. He said the findings could be beneficial for creating better human formula that promotes a healthy microbiome.

“Understanding these ‘super ingredients’ can lead to exciting possibilities, such as creating better baby formula or finding new ways to strengthen our immune systems,” Bojar said. “By understanding the powerful properties of breast milk across different animals, we can potentially design better infant formulas that mimic some of these beneficial qualities. For many babies who cannot be breastfed for various reasons, this could be a game changer.”