As the threat of drug-resistant superbugs spreads, researchers are concerned that the overuse of antibiotics may cause another, even larger public health problem: childhood obesity.

Obesity rates in the US have been consistently climbing for the past two decades, with children in underprivileged communities accounting for the most dramatic surges in weight gain. This increase parallels a wave of pediatric antibiotic prescriptions -- a trend that is only now receding due in part to concerns over anti-microbial resistance.

Experts estimate that if rates stay consistent, 51 percent of the population will be obese by 2030. The outcome of that scenario is clear: billions in health care costs and a nation of chronically ill people. However, the causes, and therefore effective interventions, are a bit more elusive, says Ihuoma Eneli, MD, Director of the Center for Healthy Weight and Nutrition at Nationwide Children's Hospital and Professor of Clinical Pediatrics.

"We know that childhood obesity isn't only caused by genes, an unhealthy diet and too little activity, but likely the combination of several complex factors -- one of which may be the frequent use of antibiotics at a young age," says Dr. Eneli. "We have biological and statistical data that suggest there may be a connection, but we are looking for answers that can help us better understand this relationship and guide clinical practice in a way that will truly reduce a child's risk for becoming obese."

Dr. Eneli is part of a national research project -- the PCORnet Obesity Observational Study -- led by scientists at Harvard Pilgrim HealthCare (HPHC), which aims to do just that. This study is a demonstration study for PCORnet, the National Patient-Centered Clinical Research Network, which is an ambitious initiative funded by the Patient-Centered Outcomes Research Institute (PCORI) to accelerate the nation's ability to conduct patient-centered clinical research more efficiently by using health information shared by patients and other clinical data.

The network of pediatric researchers across the country are some of the first to look for answers through PCORnet by combing through the medical records of about 1.6 million children from 42 different healthcare systems. For the study, scientists will follow how many times children are prescribed antibiotics during the first two years of life, and then continue to track children to ages five and 10 to see how many of them are obese (i.e., heavier than 95 percent of children of the same age and sex).

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"The study is exciting because the electronic health record lets us drill down into specifics, quickly and at relatively low cost. For instance, it's possible that certain types of antibiotics are less likely to influence weight gain versus others," says Dr. Eneli. "The study is also researching if the timing of when a baby first gets antibiotics or if the mother took antibiotics while pregnant has any impact on obesity."

The study is also unique in that parents of obese kids are considered part of the research team. A parent of a patient from the Nationwide Children's team, Doug Lunsford is serving as one of the principal investigators (PI) on the study. This parent engagement is innovative; 'PIs' historically have only referred to the lead scientist on a study. Parents like Doug have helped create the study's end goals, and most importantly, will help determine how the results are shared with families so that they can be understandable and actionable.

"End-user participation -- particularly with an issue like childhood obesity -- is an absolutely critical part of the process. It doesn't do anyone any good if we have results to share, but we do it in a way that doesn't resonate with people or help them make changes," says Dr. Eneli.

Gut bacteria influence weight

Antibiotics are a critical medical advancement that has saved countless lives, but the same biology that makes them so effective against illness could also be increasing people's chances of becoming obese.

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Babies are born with beneficial bacteria in their intestines that help digest food and keep illness-causing germs in check. This unique mix of bacteria is influenced by multiple factors, including if a baby is fed breast milk or formula or delivered vaginally or via C-section.

In the last five years, scientists have made compelling discoveries showing that there may be a connection between the amount and type of bacteria in the intestines and weight gain. When the numbers of good bacteria are depleted, other types of bacteria already living in the gut emerge and flourish.

These "new" bacteria don't cause sickness, but may increase calorie absorption, slow metabolism and cause very low levels of inflammation -- all of which appear to trigger a chain reaction that alters the behavior of fat cells. When antibiotics are prescribed, they can kill both the harmful and helpful bacteria in the body -- but they could also be changing the micro-environment of fat tissue in ways that are difficult to reverse and that lead to obesity.

"This could help explain why once a person becomes obese, it is so difficult to reverse the process. These permanent changes in metabolism make it so much harder to get and keep weight off," says Dr. Eneli.

What should parents do now?

Currently, most pediatricians are already very careful about not overprescribing antibiotics. Dr. Eneli suggests that parents should work closely with their pediatricians to make the decision together about whether or not antibiotics will provide the most benefit to the child. She notes that antibiotics don't help most upper respiratory or ear infections -- some of the most common reasons that kids are taken to the doctor's office.

Antibiotics can cause stomach upset and diarrhea; possibly because of gut bacteria changes during treatment. Some studies suggest taking probiotics or yogurt with active cultures can be helpful for restoring good bacteria in the gut after a course of antibiotics; however, there is no evidence that shows consuming either have any effect on preventing possible weight gain.

Dr. Eneli points out that there's no need to wait for the results of the national study to know how to prevent unhealthy weight gain.

"While we are still trying to answer the question about antibiotics and obesity -- there is one thing we know for sure: a diet high in refined sugars, processed grains and high fat coupled with a lack of exercise are huge risks for weight gain," said Dr. Eneli. "By giving your child healthy food choices and encouraging physical activity, parents can help kids avoid obesity."

Researchers expect their first round of data will be available early next year, and will lay the groundwork for spin-off studies that will look more closely at risk factors identified in this study.

Research reported in this article is being funded through a Patient-Centered Outcomes Research Institute (PCORI) Award for development of the National Patient-Centered Clinical Research Network, known as PCORnet. The study is also being supported the Ohio State University Center for Clinical and Translational Sciences.