Damon Runyon-National Mah Jongg League Fellow Deepshika Ramanan, PhD, has been selected as part of the 2020 class of STAT Wunderkinds, an annual award recognizing the next generation of “scientific superstars.” These researchers are blazing new trails as they tackle some of the biggest questions in science and medicine.

Dr. Ramanan’s research is demonstrating that immunological traits can be passed on from one generation to the next through mother’s milk. “When we think of inheritance, we think of genetics or epigenetics. We don’t really think about inheriting environmental factors or microbial factors, so this may be a different way to approach health impacted by traits passed on from mother to child,” she explains. Using mouse models, she has traced a protein called immunoglobulin A which binds to microbes in the gut and can influence immune cells to respond more effectively to viruses, bacteria, or even cancer. Corresponding analogs of immunoglobulins are also found in humans, suggesting the possibility that mothers can transfer traits learned during their lifetime that are not genetic to their offspring.

From mother to child

Dr. Ramanan focused on two strains of mice commonly used in the lab (BALB/c and B6), which had different levels of immune cells called regulatory T cells (Tregs). These cells are essential for preventing autoimmunity and limiting chronic inflammatory diseases, but an overabundance can limit beneficial responses against pathogens and cancer.

Her aim was to understand why these mice are different and whether their Treg levels could be changed because that could potentially be used as a therapeutic for people who have low Tregs, which can lead to Crohn’s disease or colorectal cancer.

She determined that a factor influencing Treg populations in the mice was passed on through the mother’s milk. Interestingly, when BALB/c pups were fostered by B6 mothers, the level of Tregs in the gut showed a B6 pattern that continued into adulthood. The reverse was also the case, but breastfeeding within the first three to seven days was a critical time to establish this pattern.

Dr. Ramanan then figured out that the factor passed on from mother to pup was immunoglobulin A. Pregnancy increases the number of immunoglobulin plasma cells in the intestine, which then migrate to the mammary gland and control the concentration of immunoglobulin A in the milk. Balb/c mothers have higher concentrations of IgA in milk, which is then passed on to their pups. “The takeaway here is that the moms passed immunoglobulin A in their milk and this is the factor that's affecting the Tregs in the pups for the rest of their lives. Immunoglobulin A in the intestine can coat the microbes there and this coating then determines the high or low Treg levels,” she says. This priming that occurred in the first week of the female pups' life is then passed on to subsequent generations when they become mothers.

Just the beginning of the story

As Dr. Ramanan gets ready to start her own lab in the near future, she is planning the next steps for her research. She is exploring what other factors in the milk are being passed on to the offspring that may be affecting immunity. Eventually, these findings in mice will have to be tested in humans to see if there are similar mechanisms in play.

Read more: STAT Wunderkinds 2020