Does Antibiotic Exposure Increase Risk of Obesity in Children?

The effects of antibiotic use on body weight are evaluated based on use during pregnancy and into the first 4 years of life with findings of a modest, dose-dependent association.

with Alison Tribble, MD, J. Michael Gonzalez-Campoy, MD, PhD, and Guillermo Perez Perez, MD

The more we learn about the role of the gut microbiome, the more we appreciate the importance of having this barrier to lessen the risks of obesity and type 2 diabetes, among a host of other diseases. How might exposure to antibiotics, particularly in children, act to influence the onset of obesity?

Studies on early-life exposure to antibiotics and its potential link to childhood obesity have been increasing in frequency.1-5

The link between antibiotic exposure and obesity seems real but not yet certain.

Recently, three new studies have renewed attention to this ongoing controversial interplay:

  • A national cross-sectional study of twins and siblings in New Zealand using prescription records to assess antibiotic exposures and obesity at age four years,2
  • A prospective cohort study,3 examining the association between use of antibiotics in childhood and impact on microbiome leading to increased body mass index risk of obesity
  • In addition, researchers of a third study evaluated the appropriateness of antibiotic prescribing practices in US pediatric hospitals, with researchers finding that a quarter of their young patients were receiving suboptimal therapy,4 suggesting that improvement is needed in pediatric antimicrobial stewardship.

Findings from these recently published studies,2-4 ‘’add to our understanding of the complexity of obesity as a chronic disease that is genetically-based but influenced by the environment,” said J Michael Gonzalez-Campoy, MD, PhD, FACE, medical director and chief operating officer of the Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, Minnesota, who reviewed the studies for EndocrineWeb.

Frequent Exposure to Antibiotics May Increase Obesity Risk 

In the first report,2 researchers analyzed the medical records of 132,852 women and their 151,359 children in New Zealand, tracking exposure to antibiotics during pregnancy and into early childhood.The primary endpoint was the odds of developing obesity by four years of age.

The data, collected between July 2008 and June 2011, was linked to pharmaceutical records of antibiotic prescriptions dispensed to women before conception and throughout their three trimesters of pregnancy, extending to these babies from birth to two years of age.

According to Leong et al,2 both prenatal and early childhood exposures were independently associated with obesity at age 4 years, demonstrating a dose-dependent relationship; however, a fixed effects analysis of siblings and twins produced discordant findings, with adjusted odds ratios of 0.95 (95% CI, 0.90-1.00 for maternal exposure, 1.02 (95% CI, 0.99-1.04 for children’s and 0.91 (95% CI, 0.81-1.02) for twins’ exposure.

The researchers concluded that ‘’antibiotics are unlikely to be a major contributor to childhood obesity.”

In the second study,3 the investigators examined the data for a possible association between repeated antibiotic exposure in children up to age four years and body mass index at 54 months.The study included 5,128 children, and repeated exposures were linked with a higher mean BMI-for-age z score and increased likelihood of obesity.3

Of the 5,128 children studied, 95% had an antibiotic by age 4 and 9% or 437 had developed obesity by age 54 months. Receiving more than nine prescriptions dispensed for antibiotics by the time the children reached four years was also linked with a greater likelihood of obesity compared to no exposure (adjusted odd ratio, 2.41, 95% CI, 1.07-5.41).3

Children exposed to antibiotics in the first year of life had a higher adjusted mean (SD) BMI -for-age z score than those not exposed (1.06 [0.05] vs. 0.89 [0/09] P =0.03) and those whose exposure began after the first year of life did not (1.02 [0.06] vs. 0.89 [0.09] P = 0.10).

In a point prevalence report,4 Alison C. Tribble, MD, assistant professor of pediatrics at the University of Michigan, Ann Arbor, and a pediatric infectious disease specialist, and colleagues, tracked antibiotic prescribing trends at 32 pediatric hospitals across the United States.

This research group found that among 11,784 patients who had been treated with antibiotics for an infectious use condition, 25.9% of the children were prescribed one or more suboptimal antibiotic drugs (ie, drug choice of antibiotic or wrong dose/timing). This translated to about one in three children who were hospitalized for treatment and received one or more prescribed antibiotics at any given time that did not adequately manage the condition for which the antibiotic was provided,4 according to Dr. Tribble et al.

Impact on Microbiome May Factor into Weight Gain

In an editorial accompanying the pair of New Zealand studies,5 the authors suggested that the potential role of antibiotic exposure—while ‘’neither necessary nor sufficient as a cause” of childhood obesity, cannot be ignored,5 given the mounting evidence from livestock farming, animal experiments, and human studies showing that antibiotics may cause changes in the gut microbiome that are associated with metabolism and weight gain.1

They added a caveat to the statement of possible adverse effects that there are still many aspects to be explored to gain clarity about this apparent relationship.4 “It remains unclear whether antibiotics causally influence obesity development in humans and whether particular antibiotic types or time windows of exposure are especially detrimental,” wrote Azad et al. “The nuances are important to understand because, although the associations appear to be modest, they could be meaningful at the population level.”

Since it would be unethical to randomly assign use of antibiotics to children, current research studies have been initiated to look at whether interventions to reduce antibiotic overprescribing might also result in a reduction in the rates of obesity in childhood. 

However, from existing observations of antibiotic use, there seems to be a strong need to gain more consistent accordance with the recommendations of antibiotic stewardship programs, 6 as Dr. Tribble and others have noted.

Relationship Between Antibiotic Use and Obesity 

“We now understand that the gut microbiome is very irritant as a determinant of body weight, although the precise mechanism is not yet defined. Germ-free rats that were treated with fecal transplants from obese rats developed obesity. If [the germ-free rodents] were treated with fecal transplants from lean rats, they remain lean while eating the same number of calories,”7 said Dr. Gonzalez-Campoy.

“The two major species of bacteria that determine weight status are firmicutes and bacteroidetes.8 We now have documentation that decreasing an individual’s caloric intake leads to less firmicutes and more bacteroidetes with the ratio of these bacteria presenting as the determinant of fat mass,” he said. 

“A high firmicutes to bacteroidetes ratio is associated with an increase in fat mass, and obesity, while conversely, a decrease in the ratio is associated with a loss of fat mass. These observations offer a glimpse of one mechanism whereby the use of antibiotics has a clear association with childhood obesity,” Dr. Gonzalez-Campoy added.

The research has introduced a great deal of variability in results, Dr. Tribble told EndocrineWeb. “Some [studies] have shown a clear link, while others [raise] questionable [findings of any association]. It does seem plausible but the exact link, I think, is still a little murky,” she said, adding, that any relationship is most likely a fairly modest one.

However, she said, it would be the wrong message to communicate to parents that they should reject giving their child an antibiotic, when necessary, because it might lead to overweight.

“Antibiotics alone are not responsible for the current rise in obesity,” said Guillermo I. Perez Perez, MD, research associate professor at New York University Langone Health, who also offered comment on this groups of studies. “I feel the current knowledge is still unclear as related to the use of antibiotics.”

For now, Dr. Perez told EndocrineWeb, the findings, such as they are, indicate ‘’another reason to avoid antibiotics for children unless they are critical.” And it also underscores the importance of introducing a healthy diet from early in life (including avoiding juice, and processed foods) and encouraging daily activity, (which means limited screen time that fosters sedentary behaviors).

"Regardless of the process, anything that modifies the gut microbiome has the potential to affect fat mass and metabolism," Dr. Gonzalez-Campoy said. "The observation that antibiotic use in early development is a determinant of childhood obesity may be followed by the observation that childhood obesity is predictive of adult obesity." This may be so to a point; the current concept is that adult obesity arises from "a summation of cumulative changes over a lifetime."  

As such, early childhood exposure to antibiotics as one of several possible environmental assaults may be contributory to obesity in adulthood. Sharing this insight with your patients may help them feel less blame, and give them more motivation to approach weight loss with greater empathy for themselves.

None of these individuals reported having any financial conflicts with regard to this work.

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