Healthy Weight Program Launches Study on Microbiome

Trillions of naturally occurring bacteria and other microbes coexist in the human gut and are part of how we process food and harness energy. Known as the microbiome, this complex collection’s potential role in early weight gain and obesity has become a fascinating area of scientific exploration.

Approximately 10 percent of children in the U.S. are already obese by age 2. These rates are especially concerning because research suggests that infants with rapid growth during the first two years of life may be more likely to be obese later in childhood and into adulthood. Excessive weight gain in childhood is associated with elevated blood pressure, musculoskeletal complaints, and asthma.

An interdisciplinary study team from The Children’s Hospital of Philadelphia’s and University of Pennsylvania has begun an observational cohort study that will focus on the role of the gut microbiome in the development of obesity early in life. It is a unique research opportunity because babies are born with close to sterile conditions, but they are quickly colonized with the microbes that they are exposed to in their environment.

“We are enrolling moms during their third trimester and trying to characterize their vaginal and gut microbiota, look at the transmission to infants, and follow the changes of the microbiota of infants through the first year of life to see if it correlates with weight gain,” said Babette S. Zemel, PhD, principal investigator of the Infant Growth and Microbiome (I-gram) study. “We are focusing on low-income African American families because they have the highest rates of obesity in adulthood in the U.S. We want to try to tackle this problem early if we can.”

Not only will the researchers consider the microbiome in this long-term study, but they also will have the opportunity to simultaneously investigate a number of other risk factors associated with obesity. For example, epidemiological evidence suggests that children born by cesarean section have higher rates of obesity than those who are born vaginally. This points to the hypothesis that infants who miss out on early transmission of maternal microbiota could be more susceptible to excess weight gain in childhood.

In a subset of babies, the researchers plan to observe how rapidly the infants’ microbial communities cultivate. For another subset, they intend to track any babies who are prescribed antibiotics, in order to identify fluctuations in the microbial profiles after the infants receive the medications and to see how quickly the microbes are restored.

“Fluctuations in microbial profiles could support a mechanism for the association between antibiotics and early obesity,” said Patricia DeRusso, MD, MS, director of the Healthy Weight Program at The Children’s Hospital of Philadelphia.

A recent Healthy Weight Program-funded study using electronic health records explored the potential association between repeated exposure to broad spectrum antibiotics in early ages and childhood obesity. L. Charles Bailey, MD, PhD, is the principal investigator of the study, and the results were published online Sept. 29 in JAMA Pediatrics.

An additional focus of the I-gram study will be to examine the role of multiple feeding-related factors including breastfeeding, formula feeding, sucking behavior, feeding patterns, and timing of introduction of solid foods.

Looking at the potential interaction of these novel mechanisms will help to create a detailed description of what happens in the first year of life among infants born to 300 normal weight vs. obese African American, predominantly low-income mothers. The moms will give birth at the University of Pennsylvania where study collaborators will collect samples at the time of delivery. Next, infant growth experts at CHOP will measure the infants and follow their development carefully over the next 12 months. They will use a machine called a Pea Pod to periodically measure the infants’ body composition — the amount of fat and lean tissue in the body.

“The long-term implication of this study is that if we can identify early predictors of weight gain during infancy, it is an ideal opportunity to intervene in some way,” Dr. Zemel said.

Interest in the microbiome has flourished as better tools have emerged that allow scientists to analyze the microbes’ DNA and their metabolic byproducts, which are an essential part of our digestive system. Intriguing research suggests that people who are obese have a different profile of microbiota than people who are not obese. Dr. Zemel pointed out that findings from a study of twins, in which one twin was obese and the other was not, demonstrated that a fecal microbiota transplant from the obese twin into germfree mice resulted in weight gain for the rodents.

“This adds to the evidence that there is some causal link between the gut microbiome and the development of obesity,” Dr. Zemel said.

The I-gram study is one of 10 research projects in the portfolio of CHOP’s Healthy Weight Program that aim to advance understanding of the root causes of obesity and effective models for prevention and treatment, focused on early childhood intervention.  Funding was provided by an unrestricted donation from the American Beverage Foundation for a Healthy America to The Children’s Hospital of Philadelphia to support the Healthy Weight Program.

“Obesity prevention is a signature area of our research,” said Gurpreet Kalra, MS, CCRP, research program manager for the Healthy Weight Program. “Our agenda is informed by the latest Institute of Medicine’s guidelines that stressed the lack of research on obesity prevention in very young children. Identification of novel, modifiable risk factors, which is the focus of the I-gram study, is key to obesity prevention.”

The portfolio has a comprehensive focus because obesity is a complex, multifactorial disease and uses a variety of electronic health records, social media, and community partnered strategies to conduct the research.

“We are committed to long-term studies that can more conclusively prove causality and test the effectiveness of interventions,” Gurpreet said.

Most of the studies involve children and families from neighboring high-risk populations and communities where obesity rates are among the highest in the city. The multidisciplinary investigative team includes experts in anthropology, pediatric and adult gastroenterology, endocrinology, psychology, psychiatry, obstetrics and gynecology, microbiology, genetics, public health, and biostatistics.

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