The Developing Infant: Microbe-Human Interactions for Lifelong Health

(Upbeat music) – Hi, my name is Juliette Madan I'm a pediatrician and a neonatologist so I specialize in caring for infants who require intensive care

We take care of those babies in the Neonatal Intensive Care or the NICU I started out in my training noticing very early on that babies who are healthy and babies who require intensive care had better health outcomes if they had exposure to breast milk This posed, for me, a very important question What was different about breast milk compared with formula? And why were health outcomes both in the short term and in the long term for these babies more optimal? That actually led me to create, here at Dartmouth, an infant microbiome that's housed in three separate cohorts here We have a cohort of premature infants in our NICU who we're following carefully to understand how very short term, acute life-threatening outcomes relate to changes in the microbiome

And we also study healthy babies here in the New Hampshire Birth Cohort study, which is a study of 2,000 moms and babies And in that study, we're trying to understand how bacteria colonize healthy infants and how that colonization pattern relates to health And finally, we study babies with cystic fibrosis, which is a genetic condition which leads to early onset gastrointestinal and respiratory complications that lead, unfortunately, to early morbidity and to early death The human microbiome is a compilation of bacteria that live in and on each and every one of us In fact, there are trillions of bacteria that are housed, most often, in our intestines

In adults, that human microbiome or that community of bacteria, is very stable and for you and for me, there's not much change to that pattern of microbes In new babies, the bacteria are essentially not present at the time of delivery and babies are colonized with these bacteria over the course of weeks and months in the beginning of life What our research is trying to understand is how those bacteria interact with the developing immune system and how the immune system ultimately predisposes some of our patients for diseases These can be very common conditions, like allergy to foods, which can be life-threatening, asthma, which also causes substantial problems for kids missing school and missing play time In addition, too, we're starting to understand the patterns in these bacteria also relate to cancer risk and to risk for heart disease

So our overall program is hoping to understand how colonization patterns in early life in both healthy babies and in very high-risk babies, like our patients who are born very prematurely or babies with cystic fibrosis, have patterns that might differ from healthy infants and how we might be able to change that with interventions One of my patients from early in my career in the NICU, I'll call him Matthew, he was born 10 weeks early and suffered very greatly, was unable to breathe on his own, required the support of a respirator or a ventilator, required tubes for feeding, intravenous lines for fluids, and we required a lot of intensive care to help him to survive He actually survived eight weeks through a lot of really substantial intervention and just as he was nearing, looking towards going home, unfortunately, suffered a very severe, life-threatening bacterial infection in his intestines that caused his early death This was part of my inspiration to try to understand how the colonization pattern in infants results in higher risk for mortality in our very high-risk babies, like Matthew, but also how it relates to health in our more healthy population in diseases like asthma and allergy and obesity that impact so many millions of our children in the United States In the three cohorts that I mentioned, we are collecting multiple types of biologic specimens

And doing sequencing technology similar to sequencing the human genome, we're able to sequence the bacterial genome to understand exactly what's present in and on our bodies to help understand how that interacts with our immune system and how that results in disease risk On the flip side, if we can understand that in healthy populations, we're also able to potentially optimize health for all of our patients We think about this somewhat like a vaccine or a preventative So if a baby is unfortunately in need of antibiotics in her early critical window when her immune system is interacting with these bacteria, then we could maybe tailor a specific type of intervention to help her recover her healthy bacteria in this critical period when her immune system is developing We are very hopeful that, with support from foundations and also with support from the NIH that we'll be able to continue to expand the work we do here at Dartmouth in our CF Cohort, in our Preterm Infant Cohort and in the New Hampshire Birth Cohort study to expand the work that we do to other disease processes and to truly helping to optimize the health for our infants in New Hampshire and across the United States

Thanks – Thank you so much for being here today That was a great presentation and your research is fascinating So my question for you is what does success look like in your research project, maybe five to 10 years from now that really could help patients like Matthew and maybe have saved his life? So what does that look like for you? – That's a great question So, in our Cystic Fibrosis Cohort, we have been able to identify microbes or bacteria that are missing in babies early on in life, prior to the onset of substantial interventions like antibiotics or hospitalization or changes in their diet

So in high-risk populations, like in our Cystic Fibrosis Cohort, and for patients like Matthew in the Neonatal Intensive Care Unit, our work is able to help us to lay out very clearly what patterns are different in high-risk babies and compare them to healthy populations who have very optimal health outcomes and we've actually been able to study what's missing in babies with cystic fibrosis, both in a cell model in our lab, but also in a mouse model, in collaboration with other investigators That work is helping us to understand how what's missing in cystic fibrosis leads to disease progression in early life and our goal is now to target, with specific healthy bacteria products so that we would able to correct what's missing or repair the damage from either interventions or from genetic differences or from prematurity – Juliette, you mentioned the New Hampshire Birth Cohort and I wonder if you'd be able to speak a little bit about the unique opportunity that creates to assess the environmental influences and dietary influences on the human microbiome through the developmental stages – Thanks So here at Dartmouth, I am very lucky to be the Clinical Director of the New Hampshire Birth Cohort study as well as the Children's Environment Health and Disease Prevention Research Center

And they work hand-in-hand here at Dartmouth to study very healthy birth cohort population of mothers and babies in combination so that we can look to understand exposures during pregnancy, during the process of delivery, and then through the first seven or eight years of life, in fact, to try to understand how typical exposures, such as delivery mode or feeding method with breast feeding or formula, how those things might impact the development of bacteria in the gut in addition to atypical exposures, such as antibiotics or here in New Hampshire, some of the environmental exposures that we have noticed already have impact on the succession of bacteria in the gut, things like arsenic that's in our well water here in New Hampshire in many of our homes in addition to other environmental toxins that we're studying very carefully that really do have impact on very large populations, not just here in New Hampshire So our overall goal is to help understand in detail how these exposures impact the development of the microbiome and ultimately, health outcomes – Great – That's great, well, thank you so much for being here with us today This is great work and we really appreciate your time

– Thanks

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