ReviewExploring the contribution of maternal antibiotics and breastfeeding to development of the infant microbiome and pediatric obesity
Introduction
Pediatric obesity has significant public health importance due to increasing risk of adult premature mortality, type 2 diabetes, and cardiovascular disease [1], [2]. Currently there is no universally accepted definition of obesity in children aged <2 years [3]; however, growth curves and estimates of adiposity have been associated with infant adiposity [4], rapid weight gain [5], and subsequent pediatric obesity [6]. In the USA between 2011 and 2012, 23% of children were overweight or obese entering kindergarten [7] and 8% of infants are greater than the 95th percentile of sex-specific weight for recumbent length [7]. Moreover, longitudinal data demonstrate that children obese at age 5 years are four times as likely to remain obese at age 14 years, with nearly one in three of these children delivered with a birth weight ≥4000 g [8]. Emerging evidence suggests that an altered intestinal microbiota during early life, potentially resulting from mode of delivery, maternal diet, antibiotic use, hormones, and/or breastfeeding may seed an “obesogenic” microbiome that contributes to the development of obesity in early life [9]. Exclusive breastfeeding has been associated with protection against pediatric obesity [10]; however, these observations do not appear to be universal across all populations [11]. The objective of this review is to examine the development of the infant gut microbiome concerning breastfeeding and antibiotic exposure that may influence and/or obscure the relationship between breastfeeding and protection from obesity.
Section snippets
Infant gut microbiome
The human gut microbiome is described as a community of micro-organisms that live in and on the human body [12]. In the last decade, the gut microbiota has been associated with body weight, energy homeostasis and inflammation [13]. Bacterial colonization patterns have also been associated with obesity [14]. The infant gut microbiome is influenced by several factors including genetics, gestational age, mode of delivery, feeding practices (breastfeeding vs formula feeding) [15], and exposure to
Human milk composition
The macronutrient composition of human milk (HM) is dependent upon a variety of factors including maternal environment, time of delivery, stage of lactation, maternal diet, nursing frequency, and maternal body mass index (BMI) [21]. Structure of the macronutrients in HM provides support for infant development of protective microbiota. Specifically, glycosylated proteins passed to the infant through HM act as defense mechanisms against potential pathogens within the infant gut. Whereas many of
Human milk hormones
Appetite-regulating hormones including adiponectin, leptin, insulin, ghrelin, and resistin are present in HM and have been associated with the development of pediatric obesity; however, their contribution to the infant gut microbiome is not well established [22]. Milk adiponectin is present at higher concentrations relative to other milk adipokines (i.e., leptin, ghrelin) and has been related both positively and negatively with obesity risk and adiposity in later life [26], [27], [28]. Further,
Human milk microbiome
Breastfeeding, as the initial food source for the infant, introduces new microbial communities that stimulate growth and development of the infant gut microbiome [43]. Investigations have examined the infant gut microbiome in breast- and formula-fed infants [15]; however, surprisingly little is known about HM composition and its impact on the development of the early infant gastrointestinal tract [19]. Bifidobacteria are Gram-positive bacteria that are dominant in the microbiota of breastfed
Maternal antibiotic exposure
Antibiotics utilization in the USA has increased over the past decade due to changes in lifestyle and health care systems [49]. In recent years, our ubiquitous use of antibiotics in obstetrics means that many infants are exposed to antibiotics prenatally, perinatally, and postnatally. Prenatally, maternal antibiotics are often prescribed due to urinary tract infection, sinus infection, ear infection or any other common infections. During peripartum, use of antibiotics is most likely given due
Human milk and maternal antibiotics
Importantly, states with the highest rates of both antibiotic use and obesity rates were in the Southeastern region and Appalachian counties of Tennessee and Kentucky [58]. Although the vast majority of investigations into early-life antibiotics and pediatric obesity have primarily focused on offspring postnatal exposure [59], recent data from Mueller et al. demonstrated that maternal antibiotic use during the second and third trimester of pregnancy was associated with an 84% increase in risk
Future directions
In the USA more than 10 million women are either pregnant or lactating, and antibiotics are the most frequent prescription medication in this population [65]. The health benefits of breastfeeding are well recognized; however, establishing clear anti-obesity mechanistic effects of breastfeeding remains a challenge [11]. Previous studies have collected HM samples at one point in time, rather than throughout the various stages of lactation; and longitudinal data focusing on the impact of HM
Clinical implications
Modifiable risk factors for pediatric obesity clearly include early infant diet; however, accumulating data suggest that human milk hormones and maternal antibiotics may affect the infant gut microbiome and increase the long-term offspring risk of obesity. The potentially beneficial role of human milk hormones may be yet another reason to increase human milk exposure, especially in situations of increased vulnerability to metabolic dysfunction, such as in preterm infants. Many mothers with
Conflict of interest statement
None declared.
Funding sources
None.
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