Review
Antibiotic administration and the development of obesity in children

https://doi.org/10.1016/j.ijantimicag.2015.12.017Get rights and content

Highlights

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    Antibiotic abuse can cause gut microbiota dysbiosis.

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    Antibiotic-related gut microbiota dysbiosis is associated with obesity.

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    Obesity should be considered a reason for the judicious use of antibiotics.

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    Probiotics and prebiotics can improve the balance of the intestinal flora.

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    Further studies on the relationship between antibiotics and dysbiosis are needed.

Abstract

Antibiotics are the most common prescription drugs administered at the paediatric age, however their administration can cause unwanted problems. Among these issues, antibiotic-induced gut microbiota dysbiosis has appeared as an emerging issue and has been associated with obesity. This problem is particularly relevant in children because they are frequently treated with antibiotics. Early development of obesity increases the risk of adult obesity, which is associated with the emergence of very severe clinical problems. Dysbiosis induced in the first periods of life can have the most relevant practical consequences because a decrease in the number of microbes and their substitution with other microbes dramatically modifies the development of the immune system as well as glucose and lipid metabolism. Unfortunately, not all of the mechanisms that could explain the relationship between gut microbiota modification and the development of obesity have been defined. Consequently, no definitive therapeutic approach has been elucidated. Probiotics and prebiotics could play a role in treating microbial dysbiosis because the addition of specific bacterial strains has been associated with normal weight and has been demonstrated to be useful in clinical conditions other than obesity that are caused by microbiota disruption. Considering that antibiotics are commonly prescribed and that obesity is increasing in paediatric patients, further studies specifically designed to evaluate how to disrupt the relationship between antibiotics and dysbiosis are urgently needed. Presently, paediatricians have to consider dysbiosis to be a new and serious reason for the judicious use of antibiotics in clinical practice.

Introduction

Antibiotics are the most common prescription drugs administered in paediatric patients [1] and have modified the morbidity and mortality associated with a great number of bacterial infectious diseases, with enormous advantages from a medical, social and economic point of view. However, antibiotic administration can cause unwanted problems. Among these, the development of bacterial resistance and antibiotic-related adverse events were considered the most important problems until a few years ago [2], [3], [4]. Recently, however, a series of new problems related to antibiotic-induced gut microbiota dysbiosis have emerged [5]. Of these, obesity appears to be of particular relevance.

Obesity in children is increasing worldwide. Increased weight in the first years of life has been shown to be a significant risk factor for difficult-to-treat obesity at an adult age, with the early development of type 2 diabetes, cardiovascular diseases and a number of other serious co-morbidities [6], [7]. Paediatricians must pay particular attention to the potential association between antibiotic use and obesity and consider this problem to be a new and serious reason for the judicious use of antibiotics in clinical practice. In this review, exposure of children to antibiotics will be summarised. The relationships between antibiotic administration, microbiota composition and the development of obesity will be discussed, together with potential therapeutic approaches.

Section snippets

Childhood exposure to antibiotics

Beginning in the uterus, children are exposed to antibiotics. An analysis of 987 973 pregnancies of Danish residents during the period 2000–2010 showed that 33.4% of women with a delivery had one or more systemic antibiotic treatments during pregnancy [8].

Moreover, exposure to antibiotics remains very high perinatally and in the first periods of life. A great number of mothers receive antibiotics for prophylaxis of vaginal group B streptococcus (GBS) and caesarean section (CS) delivery, although

Antibiotic use and the development of obesity in children: epidemiological evidence

The antibiotic-mediated promotion of growth in animals was shown several years ago [29] and is widely practiced by farmers to improve the growth of mammalian livestock and poultry [30]. Moreover, the association between antibiotic use and an increase in fat mass has been confirmed in experimental animals [31]. Emerging epidemiological studies have shown that this phenomenon can also occur in humans starting in the foetal stage of life. In the USA, Mueller et al. performed a cohort study of 436

Antibiotic administration, microbiota modification and obesity development: possible relationships

Initially, despite the dosages known to cause animal overgrowth being lower than those usually recommended for therapy, it was assumed that prophylactic antibiotics could influence growth [19]. However, studies carried out in germ-free (GF) animals definitively excluded this hypothesis and showed that the gut microbiota plays a relevant role in regulating body weight and conditioning glucose and lipid metabolism. GF animals require 30% more calories to maintain their body mass than conventional

Gut microbiota development and antibiotic-induced dysbiosis in children

Until recently, it was thought that that the foetus and intrauterine environment were sterile and that the intestinal microbiota would develop only at birth after passage through the vaginal canal or, in cases of CS, after contact with environmental microbes [67], [68]. However, recent data appear to indicate that maternal–foetal exchange of commensal bacteria may occur before birth via foetal colonisation.

Together with the demonstration of bacteria in amniotic fluid [69], umbilical cord blood

Possible approaches to modify gut microbiota

Several methods can be used to attempt to modify a disturbed gut microbiota. Among them, probiotics and prebiotics are largely used to improve the balance of the intestinal flora [87], [88]. Probiotic bacteria are mainly lactic acid-producing bacteria of the Lactobacillus and Bifidobacterium genera, although other micro-organisms such as Saccharomyces boulardii, Streptococcus thermophilus and Bacillus polyfermenticus have also been studied. Some of them, with differences between strains, have

Conclusions

Mainly collected in experimental animals, several data indicate that the gut microbiota plays a relevant role in conditioning body weight and that antibiotic-related gut microbiota modifications are associated with overweight and obesity. The problem is particularly relevant in children because these subjects are frequently treated with antibiotics, and the early development of obesity increases the risk of adult obesity, which is associated with the emergence of very severe clinical problems.

Funding

This review was supported by a grant from the Italian Ministry of Health [Bando Giovani Ricercatori 2009].

Competing interests

None declared.

Ethical approval

Not required.

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