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Answers to questions regarding antibiotics and increased BMI in infants and children
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When given antibiotics for their infants and children, parents may now be asking pediatricians: “Will this antibiotic make my baby fat?” Some information has recently appeared in the lay media and literature describing a potential relationship between antibiotics and obesity (eg, “Antibiotics Could be Driving Up Obesity,” ABC News, Nov. 1, 2011). During the past few years, the medical literature has also included studies on potential associations between antibiotic use and weight in infants and children.
The human microbiome
The human body harbors more than 1 trillion microbes, with these microbes outnumbering our own cells by at least 10:1. The total genome and gene products of these microbes are termed the microbiome. Interest and research in the human microbiome has increased in recent years. The Human Microbiome Project was recently established by the National Institutes of Health to characterize the microbial communities within the human body and to assess the role of these microbes in human health and disease.
The gastrointestinal tract (GI) may include the greatest number of microbes within a physiologic area of the body. The major phylum of bacteria in the GI tract includes Firmicutes (eg, Lactobacillus, Clostridium, Listeria, Helicobacter) and Bacteroidetes (eg, Bacteroides). At birth, the infant GI tract is sterile, but it quickly becomes populated with various microbial species. Several months may be required for the human microbiome to differentiate into body site-specific communities, and a core microbiome may be established throughout infancy.
However, some data suggest that the GI microbial community of children and adolescents may also differ from adults. What role does the microbiome play? It is believed that the microbiome benefits nutrition and growth (eg, fermentation of non-digestible fibers and salvage of energy as short-chain fatty acids) and is involved with production of vitamin K, regulation of intestinal angiogenesis, protection from invading pathogens, and serves a role in development of the immune response.
Edward A. Bell
Bacterial colonization: Infants and children vs. adults
Several factors may affect the specific bacteria that begin to colonize the infant GI tract. These factors are beginning to be evaluated and may include mode of delivery, type of feeding, gestational age, hospitalization and antibiotic use. Penders and colleagues assessed a variety of external factors and their effect upon the gut bacterial community in infants at aged 1 month. Fecal samples from 1,032 infants recruited from the KOALA Birth Cohort Study in the Netherlands were evaluated for various bacterial species. The most important determinants of GI microbial population included mode of delivery, type of infant feeding, gestational age, infant hospitalization and use of antibiotics by infants. Infants born by cesarean section had reduced amounts of Bifidobacteria and Bacteroides and greater numbers of C. difficile.
Infants born vaginally were more likely to harbor bacteria from the mother’s vaginal and intestinal (fecal) tract, including Lactobacillus and Bifidobacteria. Hospitalization and prematurity were also associated with greater amounts of C. difficile.
Infants born vaginally at home and breast-fed exclusively were reported to have the most “beneficial” GI microbes (greater Bifidobacteria and lesser C. difficile). Other studies have shown different results, however. For example, type of feeding (breast-fed vs. formula-fed) has not affected GI microbial colonization in other studies.
Antibiotics, GI bacteria and obesity
Several studies in children and adults have evaluated the effect of systemic antibiotic administration upon GI microbial communities. In the Penders study described above, antibiotic (mostly amoxicillin) use by infants during the first month of life resulted in decreased amounts of Bifidobacteria and Bacteroides. Other smaller studies have evaluated long-term effects of antibiotics upon fecal and GI microbial counts and have shown that the gut microbiome is quickly altered by antibiotic use and may not return to its pre-antibiotic composition when antibiotic therapy is discontinued.
Some data are accumulating in the literature that describe potential associations between the human microbiome and risk for developing overweight or obese body status. Certainly, these data are presently far from conclusive. However, they are intriguing, and this information is appearing in the lay media and literature. Animal studies with mice and rats provide additional interesting data.
Mice GI bacterial communities appear to be similar to humans, with a preponderance of Firmicutes and Bacteroidetes. Studies of obese mouse models demonstrate that when GI microbial communities from obese mice are transplanted into germ-free mice, weight and adiposity increases without increases in food intake, as compared with transplantation of lean mice GI microbial communities.
Several studies have evaluated potential associations between child obesity and various factors, including GI resident microbes. Ajslev and colleagues assessed delivery mode, maternal pre-pregnancy BMI and early (younger than aged 6 months) use of antibiotics to body weight at 7 years of age. A total of 28,354 child-mother pairs from the Danish National Birth Cohort were studied. The effect of antibiotic use differed by the mother’s weight: An increased risk of being overweight at age 7 years was found in children given antibiotics of normal weight mothers, and a decreased risk of overweight was found in children given antibiotics of overweight mothers.
Although this study included a large number of participants, it is limited by its collection of some data by self-reporting (for antibiotic use and child height and weight). Some data are also available from studies that have assessed GI microbes in overweight children and adults. In an evaluation of overweight 7-year-olds (n=49) selected from a previously studied prospective follow-up study, normal weight children were matched for various potential modifying factors, including use of antibiotics during infancy. Fecal samples were obtained at 6 and 12 months. Overweight children had a lower amount of Bifidobacteria and a greater amount of Staphylococcus aureus than normal weight children (Kalliomäki).
In a small study (n=12) of overweight adults, GI bacteria were assessed for 1 year and evaluated with intentional weight loss. The amount of Bacteroidetes increased and was positively correlated with weight loss (Ley).
Data inconclusive
The studies and data described above, although intriguing and interesting, do not prove that antibiotics administered to infants and children increase a risk for development of overweight body mass. Data of GI microbial species in animals and humans, and body mass, may indicate an important association, although many other influencing factors are likely important as well. Antibiotics have been shown to alter the GI microbiome, with changes that may persist for several years or more. How these changes may be related to body mass are not well defined. More studies are needed, including large epidemiologic studies. GI bacteria can be one of many factors to affect energy production and storage, and so a potential relationship with antibiotic use and weight has some basis for support.
There is no doubt, however, that antibiotics have had a great positive influence on human morbidity and mortality. As this column has stated on numerous occasions, antibiotics should be used wisely and only when medically necessary. Their potential relationship to overweight body mass may show some day to be yet another reason to adhere to this paradigm.
References:
Ajslev TA. Int J Obes. 2011;35:522-529.For more information:
Edward A. Bell, PharmD, BCPS, can be reached at: Drake University College of Pharmacy, 2507 University Ave, Des Moines, Iowa 50311; email: ed.bell@drake.edu.
Disclosure: Bell reports no relevant financial disclosures.