PROVIDENCE – Everywhere you looked, dignitaries were beaming, their faces lit up with genuine, bright smiles, as if it were Christmas Day, and they had just opened up the biggest and best present ever: a $12.5 million gift by Alan Hassenfeld and his family to create the Hassenfeld Child Health Innovation Institute in Rhode Island, announced at a State House ceremony on Sept. 28.

That generous gift, in turn, will be matched by Brown University, bringing an investment totaling $25 million to the new collaborative approach to children’s health, pledged President Christina Paxson when she spoke at the ceremony in the State Room. [Where that additional money from Brown will come from has not yet been identified.]

In addition to Hassenfeld and Paxson, the dignitaries who spoke at the podium included Gov. Gina Raimondo, Brown University Chancellor Thomas Tisch, Dr. Phyllis Dennery, pediatrician-in-chief at Hasbro Children’s Hospital, and Dr. Maureen Phillips, the executive chief of obstetrics and gynecology at Women & Infants Hospital.

Acknowledged in the audience were Terrie Fox Wetle, dean of Brown’s School of Public Health, and Dr. Jack A. Elias, dean of Medicine and Biological Sciences at Brown, and Elizabeth Burke Bryant, executive director of Rhode Island KIDS COUNT.

The work of the new institute, Elias said in the lengthy four-page news release, “will contribute to our understanding of the genetic, prenatal and early life factors associated with health problems of children,” helping to develop effective new strategies for prevention and treatment.

The new institute will focus on the urgent health needs of children, termed “the smallest state’s smallest resident,” targeting the three current childhood plagues of autism, asthma and obesity.

More precisely, the institute’s first three initiatives will be:

•    A precision medicine approach to autism, building on the registry of more than 700 families diagnosed with autism spectrum disorders developed by a Rhode Island consortium.

•    A healthy weight, nutrition and physical fitness approach to obesity, building on the Weight Control and Diabetes Research Center at The Miriam Hospital.

•    A childhood asthma research innovation program, looking at genes, stress, and environmental factors, digging deeper into the complexities of asthma’s causes and treatment.

The initiatives will be supported by the development of a new Rhode Island cohort of women and children to be developed by Phillips, creating a long-term research database. In addition, the institute will create a core research and evaluation group to support the broad range of ongoing work. 

In a brief interview following the event, Hassenfeld said that the initial focus will not be on creating a separate building to house the new institute.

“The vision is: we know the silos we want to work under, we’ve got space now, let’s not worry about a separate building,” Hassenfeld told ConvergenceRI. “I think in time, that will happen, Richard; this is not about building buildings. This is about doing the basic research. Because, if you look at the numbers in autism, if you look at asthma, or if you look at obesity, it’s at epidemic proportions. The numbers are staggering.”

Collaborative research
The new institute represents the kind of collaborative research, clinical and policy approach in Rhode Island that has often been talked about but not, as yet, implemented.

The initiative, proclaimed the explanatory program at the Sept. 28 announcement, “will integrate research, clinical practice, public health efforts and educational programs” to achieve four lofty goals:

•    Improve the health of children, making Rhode Island’s communities among the world’s healthiest places for children and families.

•    Address the issue of poverty and how it impacts child health.

•    Serve as a national and international model for what can be achieved in child health.

•    Train the next generation of child health leaders

In an interview following the event announcing the new institute, Paxson elaborated on the nature of the collaborative enterprise envisioned.

“This is a man that is passionate about improving the lives of children,” Paxson told ConvergenceRI. “That’s what he cares about; that’s what this gift is about.”

His vision, Paxson continued, “was that this should be a collaborative enterprise; he understands the power of combining critical areas [of health care] with research.”

For Brown, this approach fits perfectly with the university’s mission, Paxson told ConvergenceRI. “If you look at our strategic plan, everything we’re doing is about integration, about bringing people and ideas from different disciplines together. This is almost a perfect example of everything we want to do, bringing people and ideas together to make a difference in the world.”

In response to a question about how this effort fits into Brown’s strategy to leverage its research potential, Paxson said: “This does fit into Brown’s aspirations to be both a great university and a wonderful education institution; we care very much about both of those things.”

What we’re very, very good at, she continued, “is collaboration and integration.” She cited the collaborative work in brain science at Brown as a good example of how bringing research and education together, working with the community, can create greater impact.

What’s missing?
The one area of study not included in the initial discussions of autism, asthma and obesity and the initiatives to address these epidemics in children’s health is the growing body of scientific evidence of a direct relationship in the prevalence of these diseases with the microbiome of gut bacteria, what has been termed by some researchers as the “forgotten organ” in the human body.

Indeed, just two days after the creation of the new Hassenfeld Institute was announced, a new study was published in Science Translational Medicine on Sept. 30 that found that infants who are at high risk for asthma displayed low levels for four specific gut bacteria.

While previous research had linked gut microbes to asthma, the new study attempted to identify specific bacteria involved. “Our advance was to put a name to some of the bacteria and to emphasize the 100-day window” after birth when newborns crucially need to be exposed to them, Stuart Turvey, pediatric immunologist at the University of British Columbia and co-author of the study, told the Wall Street Journal.

The Wall Street Journal story quoted Martin Blaser, a microbiologist at the NYU Langone Medical Center, who wasn’t involved in the Science Translational Medicine paper. “There’s more and more evidence that modern illnesses derive from this loss of microbes — especially early in life,” Blaser said. “The good germs are the ones we get from mom, and those guys [the good bacteria] are disappearing.”

A quick Google search will also identify numerous other studies that connect gut bacteria with autism and with obesity.

While all these diseases, including asthma, have a distinct genetic component, the new scientific research findings are making progress in identifying environmental factors, including endocrine disrupting chemicals and missing beneficial bacteria, that appear to contribute to the incidence and growing prevalence of these diseases.

What are the questions to ask?
As the new Hassenfeld Institute begins to launch its work on asthma, autism and obesity, ConvergenceRI sought out two leading epidemiologists at Brown University to ask them about the questions that researchers should consider asking in regard to the gut microbiome and its relationship to these diseases.

Joseph M. Braun is an assistant professor in the Department of Epidemiology at the Brown University School of Public Health. His work is focused on studying whether early life environmental chemical exposures impact children’s health, with a special interest in studying obesity and neurodevelopmental disorders, such as ADHD and autism. He is also interested in identifying modifiable sources of environmental chemical exposures in pregnant women and children.

ConvergenceRI: In setting up a new research cohort for mothers and children in Rhode Island, what are the kinds of information you would want tracked in relationship to gut bacteria and endocrine-disrupting chemicals? And, beyond identifying links to gut bacteria with the development of asthma, autism and obesity/diabetes, what should researchers be looking at as potential catalysts for these diseases?
BRAUN: I will try to answer both questions at once. One important point; I would not limit things to endocrine disruptors. Other chemical exposures, like metals and air pollutants, are also on the list of agents that affect child health.

New studies of prenatal environmental exposures, the microbiome, and infant/child health will require new prospective birth cohorts. These cohorts, like the one being proposed in Rhode Island, should include the collection of biospecimens from women during pregnancy.

The most obvious candidates for examination in relationship to the microbiome would be antimicrobial chemicals, e.g., parabens [a preservative used in cosmetics] or triclosan [an antibacterial compound].

Dr. Simin Liu, professor of Epidemiology at the School of Public Health, professor of Medicine at the Warren Alpert School of Medicine, and director of the Laboratory of Molecular Epidemiology and Nutrition at the Center for Cardiometabolic Health, has worked extensively in attempting to unlock the genetic links between Type 2 diabetes and heart disease. [See link to ConvergenceRI story below.]

In China, there are now estimates that some 100 million people have Type 2 diabetes, according to Liu. “I would argue that diabetes is the key epidemic of our time, especially if you look at it from a global perspective,” Liu said in a previous interview with ConvergenceRI. “About 70 to 80 percent of the people who have diabetes ultimately die from heart disease, and they have a greater [likelihood to develop] a number of cancers.”

ConvergenceRI: In terms of gut bacteria, what do you think researchers should begin to look at in studies, based on your work with diabetes?
LIU: Based on our own work this past decade, one of the most important areas of research ought to be to improve the measurement and classification of gut bacteria, while, [at the same time], truly appreciating the dynamic nature of gut bacteria interacting with the host as well as the environment, including both dietary and endocrine-disrupting chemicals [EDCs].

If this gut bacteria work is viewed in the context of other major improvements in our understanding of cardiometabolic health, then we should also carefully tease out potential sex-specific differences.

Indeed, one of the most important advancements in our understanding of the clinical sex differences in cardiometabolic health has been sex-steroid biology as it relates to clinical risk stratification and interventions.

ConvergenceRI: In terms of your work with the women’s cohort from California, as the work begins to develop a Rhode Island cohort study, what are the kinds of research focus that would be helpful to begin to track?
LIU: Our research team has been at the forefront of that work using prospective epidemiologic, clinical and basic experimental means. For example, our work and colleagues have implicated an important role of sex hormones in determining future risk of cardiometabolic disorders using several large cohorts of men and women. Ultimately, similar strategies that integrate epidemiological observations, clinical and basic experimental studies, should become standard in pushing this field forward.

ConvergenceRI: Are there specific endocrine disrupting chemicals to gut bacteria that researchers should be looking at in terms of autism, asthma and obesity/diabetes?
LIU: Yes. Endocrine-disrupting chemicals, particularly phthalates [esters used to soften plastics], and nutritional factors that may interact with gut bacteria, such as lignans, that are abundant in plants.

But, for now, it is important to examine the entire class systematically and comprehensively in well-characterized cohorts of both adults and children across diverse ethnicities and sexes.