The Microbiome’s Role in an Infant’s Developing Immune System

 

The role bacteria play in human health—what’s termed our microbiome—has been much in the news lately. Each person is host to a unique assortment and concentration of over 100 trillion bacterial cells, most of which are beneficial. For example, the bacteria in our gut help us digest food and produce some of the vitamins we require. They also have a strong influence on everything from mental health to the immune system.

Dr. Kate Powis
Dr. Kate Powis (photo by Kent Dayton)

Dr. Kate Powis, a clinician and researcher at the Harvard T.H. Chan School of Public Health AIDS Initiative (HAI), is studying the gut microbiome of HIV exposed but uninfected (HEU) infants. These HEU babies are born to HIV-positive mothers, and even though the babies don’t have the virus, they are two to three times more likely to die in the first two years of life than babies born to HIV-negative mothers. Over 1.5 million HEU children will be born this year.

Powis summarized the situation, “We’ve made great strides in preventing mother-to-child transmission of HIV, but if you win the battle in terms of preventing transmission and these kids still die, we’ve achieved nothing.”

Researchers don’t yet understand why HEU infants suffer from such a high mortality rate, but Powis and others suspect that because these children are dying of infectious causes, there’s something wrong with their immune systems. Research has shown that people suffering from diseases as varied as asthma, inflammatory bowel disease, and autoimmune diseases have a significantly different gut microbiome than healthy people. “We realize there is this cluster of bacteria that is representative of overall good health and when clusters are altered from that, we have, in general, disease—an unhealthy state,” said Powis.

“We know that an infant’s gut microbiome helps train the immune system in the first year of life, so could it be that the gut microbiome of these kids is altered because it’s inherited from an immune-compromised mother,” hypothesized Powis. “An altered gut microbiome that does not train the immune system properly or in a timely manner may be partly responsible for these kids getting sicker with pneumonia or diarrhea and dying.”

Powis is testing that hypothesis in a new study just beginning in Botswana. She’ll examine the evolving gut microbiomes of 48 HEU breastfed infants and compare them with 44 similar breastfed infants who weren’t exposed to HIV. To do this, she and her team will collect stool samples from the infants at delivery and through their first year of life. They’ll also collect vaginal and rectal samples from the mothers at delivery, as well as breast milk samples at delivery and one month later to better understand how a mother’s microbiome influences the early development of her child’s microbiome.

Dr. Max Essex
Dr. Max Essex

“A complicated mixture of things is going on between a person’s microbiome and immune response,” said Dr. Max Essex, Chair of the Harvard AIDS Initiative. “If you add in exposure to HIV, it further alters and complicates the system. Kate’s study should give us new information about how and why people can control infections in some cases and can’t as well when the immune system is compromised.”

“If our findings support the hypothesis that the immune system is taking a hit because of the altered microbiome,” said Powis, “the next step could conceivably be an intervention study with probiotics for the infant.” In the future, something as inexpensive as a probiotic tablet or a cup of yogurt, which is packed with healthy bacteria, could improve a youngster’s health.

Powis is using state-of-the-art technology to investigate the developing immune systems of this highly vulnerable group of children. “It’s the ability to quantify bacteria that has allowed us to realize how important a role the microbiome is playing in shaping the immune system and health of the individual,” said Powis. “Techniques have advanced rapidly in the last several years. We can now sequence the DNA of bacteria in the gut down to the species level to determine how many of each type of bacteria is in the gut.”

“We could not have done this kind of research ten years ago because it would have cost far too much to sequence the DNA and to interpret that information,” said Essex. “We’ve seen major reductions in the cost of sequencing and for the analyses of the big data sequencing produces.”

Kate’s study is funded by the U.S. National Institute of Allergy and Infectious Disease. Her findings should be available in 2017.

Title photo: iStock © Gilles Paire

About Martha S Henry

Martha Henry is the Director of Communications for the Harvard T.H. Chan School of Public Health AIDS Initiative.