Open access peer-reviewed chapter

Human Gut Microbiota and Obesity During Development

Written By

Tomás Cerdó, Alicia Ruiz and Cristina Campoy

Submitted: 17 May 2016 Reviewed: 22 September 2016 Published: 22 March 2017

DOI: 10.5772/65928

From the Edited Volume

Adiposity - Omics and Molecular Understanding

Edited by Jan Oxholm Gordeladze

Chapter metrics overview

2,727 Chapter Downloads

View Full Metrics


Obesity, particularly in children and adolescents, has become a significant public health problem that has reached “epidemic” status worldwide. The etiology of obesity is complex and involves lifestyle factors that are challenging to modify. The intestinal microbiota contribute to protection against pathogens, maturation of the immune system, and metabolic welfare of the host but, under some circumstances, can contribute to the pathogenesis of certain diseases. Over the last decade, novel evidence from animal and human studies has identified associations between human intestinal bacteria and host metabolism and obesity. Infancy is a critical period in the development of the gut microbiota: initial colonization is influenced not only by a number of early-life exposures, including birth mode, infant nutrition, or antibiotic use, but also by maternal factors during pregnancy, including maternal BMI, nutrition, gut microbial composition, and drug exposure, among others. Thus, an adequate nutritional and microbial environment during the perinatal period and early life may provide windows of opportunity to reduce the risk of obesity and overweight in our children by using targeted strategies aimed to modulate the gut microbiota during early life.


  • obesity
  • gut microbiota
  • early life
  • pregnancy
  • prebiotics
  • probiotics
  • antibiotics

1. Introduction

Obesity has become a major global health challenge because of the established health risks and substantial increases in prevalence. Urgent global action and leadership is needed to help countries to more effectively intervene [1]. This increase runs in parallel to an increase in the obesity during pregnancy; moreover, due to the adverse effects that this condition has on both the mother’s and offspring’s health, infant obesity has become a highlight topic of study [2].

It is well known that the physiology during pregnancy differs between obese and normal-weight women. Obesity is associated with increased insulin resistance, adverse effects in implantation and placentation processes, growth, development and metabolism alterations of the fetus, and even impact on the offspring gut microbiota [3].

Until now, studies focused on the origins of obesity were oriented towards dietary excesses (processed sugars, fat, and proteins) [4] or host genes [5]. But recent studies have shown changes in gut microbiota associated to different diseases, like obesity, metabolic syndrome, or type I [6] and type II diabetes [7]. The community of microorganisms living in a specific environment is known as microbiota. These microorganisms include bacteria, Archaea, viruses, and some unicellular eukaryotes [8]. The collective genomes of the microorganism that constitute the microbiota are known as microbiome [9]. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotics, and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens [10]. In fact, some of these microorganisms residing in the gut encode proteins involved in functions important for the host’s health, such as enzymes required for the hydrolysis of otherwise indigestible dietary compounds, and the synthesis of vitamins [9]. Since the 1990s, our knowledge of the complexity of this ecosystem has increased due to the advances in culture-independent techniques. These new techniques are fast, facilitate high throughput, and identify organisms that are uncultured to date and present in the gut microbiota; recently, by using these techniques, it has been shown that alterations in the gut microbiota composition and function are associated with certain disease states, such as obesity [11]. With the increase in knowledge about gut microbiome functions, it is becoming increasingly more possible to develop novel diagnostic, prognostic, and most important therapeutic strategies based on gut microbiota manipulation.

Focused on obesity, it has been shown that certain bacteria metabolize different nutrients more efficiently than others, increasing the absorption of calories from the diet and the amount of energy usable for the host, which contributes to fat deposition [12]. Many studies have been performed in order to link this disease with changes in the composition of the intestinal microbiota [13]. Several studies have shown increased ratio in the proportion of Firmicutes/Bacteroidetes in genetically obese mice (ob/ob) and obese humans [14, 15]. However, other studies have failed to confirm these findings and showed variable patterns in the composition of the microbiota in obese humans [13]. Within the studies cited above, it is clear that the gut microbiota plays a role in obesity and metabolic disease, but it is difficult to draw definitive conclusions about the importance of certain bacterial groups. It is therefore very important to identify the active bacteria that cause dysbiosis in the gut microbiota in order to design therapeutic strategies for long-term protection against obesity. Quantitative and qualitative alterations in the composition of the gut microbiome could lead to pathological dysbiosis.

The microbiota colonization of the maternal intestine influences offspring’s metabolic and immune system development [16]. Besides, although the microbiota-gut-brain axis is not a new concept [17], in the last years there are growing interest in studying the influence of the microbiota in children neurodevelopment by analyzing the microbiome impact on eating behavior, infant cognitive function, and brain structure and function [18]. However, the mechanisms by which maternal microbiota may contribute to health programming in the offspring are still unknown. The type of delivery (vaginal or caesarean section), diet [breast milk or formula], and antibiotics exposure have an influence on the offspring’s immune system that may promote the development of chronic inflammation, leading to allergies, autoimmune diseases, like diabetes mellitus or rheumatoid arthritis, or noncommunicable diseases such obesity and their comorbidities in children [1921].

In the present chapter, we aimed to update the knowledge about the factors involved in gut microbiota establishment during perinatal life, infancy and early childhood, and the relationship to obesity development.


2. Maternal environment

There is evidence for the importance of the prenatal period in the health and development of offspring throughout childhood and adult life [22].

In the periconceptional period, and during pregnancy and lactation is necessary to acquire the total nutrient requirements, which are associated with mother’s lifestyles and health [23]. These requirements include specific amounts of iron, vitamins (D, C, and B), calcium, folic acid, essential fatty-acids, and others, which will increase along pregnancy [24]. Furthermore, it has been demonstrated that bad habits like smoking, use of illegal drugs, consumption of caffeine and alcohol, or overweight/underweight are related to conceiving problems [25].

During the first trimester of pregnancy, the mother is under anabolism, increasing maternal fat and nutrients storage to meet the fetus-placental and maternal requirements during gestation and lactation [26]. When a deficit or overabundance of nutrients arrives to the fetus, it has to adapt itself to the new metabolic status, changing its physiology and metabolism constantly [27].

It is noteworthy that due to fetal programing, obesity may become a self-perpetuating problem, because children of obese mothers may themselves be vulnerable to becoming obese and more likely to have offspring who share this vulnerability, but the mechanisms behind this association are not fully elucidated [28].

One hypothesis to explain the influence of the mothers’ weight on their children is the transmission of obesogenic microbes from mother to her offspring; in this situation is also very important the etiology of such maternal obesity and others factors like socioeconomic status or environmental factors [29].

On the other hand, a meta-analysis including nine studies has shown an increased risk of stillbirth in obese pregnant women compared to normal-weight pregnant women [30].

It has been demonstrated that a high body mass index (BMI) and an excessive weight gain during pregnancy are associated with disturbances in the maternal gut microbiota, which will influence the development of gut microbiota in the infant [31].

Infant gut microbiota will not be only influenced by mother’s BMI, but also by the mode of delivery [32]. A study indicated that excess maternal prepregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, enriched in genus Bacteroides and depleted in genus Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus [33].

Subsequent to delivery, it has been shown that the type of feeding is one of the major factors modulating infants gut microbiota and it will be discussed in Section 4.

The establishment of the microbial community allows the maturation of the immune system as it has been demonstrated in germ-free (GF) animal models, where commensal microorganisms are required for the development of a fully functional immune system, which affects many physiological processes within the host [34].

In conclusion, the mother environment influences the offspring phenotype of her offspring, independently of his genotype. So, not only genetics will influence offspring gut microbiota development, but also mother’s lifestyle before, during, and after pregnancy.


3. Gut colonization and microbiota establishment in infancy

The first few weeks of life are very important for the gut colonization in the infant. This process will be influenced by maternal factors (weight gain during pregnancy, BMI, nutrition, microbiome composition), intrauterine state (microbiota of amniotic fluid), type of delivery (caesarean or vaginal), type of feeding later (breast milk or infant formula), and antibiotic exposure, among others (Figure 1).

Figure 1.

Maternal and environmental elements affecting the onset and modulation of the gut microbiota in the newborn infant. A plethora of factors during pregnancy can negatively influence the neonate’s gut microbiota composition and function. Furthermore, environmental factors, such as mode of delivery and feeding modality can significantly drive the neonate’s gut microbiota.

Traditionally, the placenta had been considered a sterile organ but current studies have reported the existence of a placental microbiome [3537]. Although the origin of the bacteria colonizing the placenta is unclear, it has been shown that the microbial community is represented by members of nonpathogenic bacteria from the phylum Proteobacteria, Firmicutes, Bacteriodetes, Fusobacteria, and Tenericutes [38].

Recently, placenta microbiota has been associated with preeclampsia development during pregnancy and with preterm birth, which highlights the importance of the close relationship between the microbiota and pregnancy [39]. A placental dysbiosis during pregnancy as a consequence of excess weight gain could have a major influence on the colonization and establishment of gut microbiota community on the infant [40].

Because these findings are very recent, the effects of the bacterial profile modification by probiotic supplementation during pregnancy and the effects on placental microbiome modulation are still unknown and further studies are needed.

After birth, it is known that meconium is not sterile and harbors a particular microbial community, characterized by a higher abundance of Firmicutes compared to Proteobacteria in early fecal samples [41].

A study showed that the mode of delivery (caesarean or vaginal) did not affect the diversity of the microbiota from meconium, in contrast, these samples presented a lower species diversity and a higher variation among samples in comparison with adult feces [42]. These results indicate that the microbial contact during perinatal life may imprint the offspring microbiota and immune system in preparation for the much larger inoculum transferred during vaginal delivery and breast-feeding.

As mentioned in the previous section, the mode of delivery is going to favor the establishment of a specific microbiota. Previous studies have demonstrated that gut microbiota of infant born through vaginal delivery is similar to maternal gut and vaginal microbiota; conversely, the infants born by caesarean section have a gut community more similar to bacteria from maternal skin or the hospital environment [43].

Regarding the mode of delivery, epidemiological studies suggest that caesarean delivery is associated with increased risk of overweight and obesity later in life [44]. A study has found that caesarean section delivery was associated with adiposity at 6 weeks of age, being this association stronger in children born from obese mothers and having higher risk of obesity and overweight at 11 years old [45]. Although the mode of delivery may affect the colonization of the intestinal microbiota in the baby and will increase the risk for later obesity development, it has been found that perinatal exposition of the infant born by caesarean section respect to the vaginal discharge, can partially restore its gut microbiota and resembles to babies born by vaginal delivery avoiding the problems that this entails [46].

The microbiota of the babies by the end of the first year of life presents a different microbial profile in comparison to adults. The initial gut composition of the infant is simple, dynamic, and very unstable and undergoes marked fluctuations influenced by external factors [47]. At the beginning, the gut environment is aerobic, but through colonization, the oxygen level is reduced generating a suitable environment for the growth of anaerobes [48]. The intestinal microbiota of neonates is characterized by low diversity and a relative dominance of facultative anaerobes of the phyla Proteobacteria and Actinobacteria [49]. After birth, the phyla Firmicutes and Bacteroidetes increase their diversity and dominance, reaching over 3 years old a total resemblance to the adult in terms of composition and diversity [50]. These results indicate that dietary intake during the first 1500 days of life is a critical factor in the establishment of gut microbiota community and its role in the development of obesity is a matter of research and discussion.


4. Type of infant feeding

Another important factor modulating microbial colonization in infants is the type of feeding. The diet during early life will influence on the establishment and composition of the gut microbiota during childhood and even adult life [51]. Breast milk meets the infant’s needs by providing nutrients appropriate to the infant’s developmental stage, as well as growth factors, antimicrobial peptides, and proteins to support their developing immune system. Even though breast milk provides all the necessary nutrients for a suitable development of the baby, many babies cannot take it for several reasons and they are fed with infant formulas. Infant formulas provide a greater weight gain and increase the risk of obesity, hypertension, and diabetes [52]. Therefore, it is necessary to continue studying the composition and the positive effects of breast milk versus milk infant formula in order to better understand the beneficial role of breast milk on offspring’s health to improve the outcomes in the formula-fed infants.

Breast-feeding brings clear short-term benefits for child health by reducing mortality and morbidity from infectious diseases. There is evidence on the effects on child health and growth of exclusive breast-feeding for 6 months. Kramer et al. showed that infants who were exclusively breast-fed for 6 months experienced lower morbidity from gastrointestinal and allergic diseases, while showing nondeficits in growth rates to non–breast-fed children [53]. Based on such evidence, WHO and UNICEF recommend that every infant should be exclusively breast-fed for the first 6 months of their life; continued breast-feeding for up to 2 years or longer is also recommended [54]. Also, there is evidence of long-term benefits of breast-feeding such as increased school achievement and performance in intelligence tests, reduced mean blood pressure, lower total cholesterol, and a lower prevalence of overweight and obesity leading to lower incidence of inflammatory bowel diseases, type 2 diabetes, and obesity later in life [54, 55].

Human milk is a dynamic fluid that contains many hundreds to thousands of distinct bioactive molecules that confers beneficial properties for infants. Human milk changes in composition from colostrum to late lactation, and varies within feeds, diurnally, and between mothers [56].

The composition of this complex mixture differs also during the lactation period, from colostrum through transitional to mature milk. Colostrum is produced during the first days of postpartum, it contains high amounts of secretory IgA, lactoferrin, leukocytes, and epidermal growth factor. Transitional milk typically occurs from 5 days to 2 weeks postpartum, it shares some of the characteristics of colostrum but there is an increase in milk production to support the nutritional and developmental needs of the rapidly growing infant. By 4–6 weeks postpartum, human milk is considered fully mature and it remains stable in composition over the course of lactation [5759]. Thus, infant formula should adapt to different physiological and nutritional needs of the growing baby.

Regarding the gut microbiota acquisition, the first colonizers of the infant gut are facultative anaerobes including Staphylococcus, Streptococcus, Escherichia coli, and Enterobacteria that will be later replaced by strict anaerobes that dominate the gastrointestinal tract, primarily Clostridium, Bifidobacterium spp., and Bacteroides [60]. This change in dominant taxa representation can be attributed to the introduction of breast milk or formula-feeding, signifying the first diet-related colonization event in the infant gut microbiome [61, 62]. Breast milk has been shown to be an excellent and continuous source of potentially beneficial and commensal bacteria, including Staphylococci, Streptococci, lactic acid bacteria, and Bifidobacteria, with bacterial cell numbers reaching 103–105 ml–1 of breast milk. Although the commensals’ origin is unknown, it is inevitable that bacterial from mother’s skin are transferred to the baby during breast-feeding, but there is also other hypothesis wherein bacteria from the maternal gut may reach the mammary glands via maternal dendritic cells and macrophages [63]. More than 700 species of bacteria have now been identified in human colostrum and breast milk, including multiple species of lactic acid bacteria as well as species typically colonizing the oral cavity of infants [64].

The presence of Bifidobacteria in breast milk is important for the colonization of the infant gut, since it mediates the activation of IgA-producing plasma cells in the human neonatal intestine. It is well established that a gut microbiota dominated by Bifidobacteria typifies that of the healthy breast-fed infant [65]. There are conflicting results regarding differences in the relative abundance of these bacteria between breast- and formula-fed infants. Many studies have reported that formula-fed infants display dominance of Bifidobacterium spp. similar to what has been observed in breast-fed infants [61, 66]. However, another study reported approximately double the count of Bifidobacterium in breast-fed infants compared to those formula-fed [67].

Comparisons between breast-fed and formula-fed infants show that breast-fed infants tend to contain a more uniform population of gut microbes dominated by Bifidobacteria and Lactobacillus [67], whereas formula-fed infants exhibit higher proportions of Bacteroides, Clostridium, Streptococcus, Enterobacteria, and Veillonella spp. [6669].

Although infant formulas have evolved greatly during last years, a formula providing exactly the same benefits than human milk has not yet been developed. Among others, human milk contains substantial quantities of complex nondigestible oligosaccharides (known as human milk oligosaccharides, HMOs). HMOs are considered a type of prebiotics as they promote the growth and proliferation of beneficial commensals and, consequently, prevent pathogen colonization of the infant gut and exert positive health effects [70]. Thus, the chemical composition of breast milk does influence the gut microbiome through supplying oligosaccharides that are selectively utilized by specific bacteria in the gut [60].

Another way to modify the gut microbiome is by the administration of probiotics. Probiotics are defined as “live microorganisms which when administered in adequate amounts, confer a health benefit to the host” [71]. Lactobacillus and Bifidobacterium species isolated from human milk are the most commonly used probiotic strains. They exert beneficial properties in the gut by suppressing the proliferation of pathogenic microbes, has been extensively studied [72]. For this reason, another area of research regarding formula enrichment is in HMOs and probiotics and their effects on the infant gut microbiota.

Certain gut-associated bacterial populations such as Bifidobacterium spp. possess gene clusters dedicated to the metabolism of HMOs [73, 74]. Degradation of these compounds produces lactate and short-chain fatty acids (SCFA), which in turn generates an acidic environment that prevents pathogen invasion [75]. Besides Bifidobacteria, HMOs may be consumed by other species such as Bacteroides spp. (e.g., Bacteroides fragilis and Bacteroides vulgatus) that consumes a broad range of HMO glycans [76]. Thus, HMOs play an important role in the gut colonization of the infants.

Among the most common prebiotics are fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), inulin, and lactulose. The prebiotic mixture of 90% GOS plus 10% FOS has been assessed to be safe when added to infant formula [77]. Several randomized controlled trials have been made to evaluate the efficacy and safety of prebiotic supplementation in infant formulas [78, 79]. After compiling data of these trials into a meta-analysis, weight gain [weighted mean difference 1.07 g/day] was significantly higher among formula-fed infants supplemented with prebiotics compared to the placebo group [80]. In addition, a large number of clinical trials in term of infants have shown controversial results related to the increase in Bifidobacteria in feces due to supplementation of infant formula with GOS and FOS. A systematic review published by Rao et al. [78] reported that some of the randomized controlled trials (RCTs) showed a trend of increasing Bifidobacteria counts in formula supplemented fed infants, and another systematic review published by Mugambi et al. [81] failed to show the increase in Bifidobacteria or Lactobacillus or the decrease of pathogens in infants fed with prebiotic supplemented formula.

Nonetheless, there are promising results from studies which have assessed the effect of prebiotic supplemented formulas on the gut microbiota of infants. Prebiotics are able to change gut metabolic activity, bring stool consistency, and defecation frequency closer to that of breast-fed infants. Other outcomes included better weight gain and softer stools, and a significant reduction in stool pH for infants who received prebiotic supplementation [78, 81]. Moreover, prebiotics have been used to prevent or treat obesity. Compared to probiotics, human studies with prebiotics have shown more promising results in obesity management, with reductions in body weight and fat mass in adults [8284] in contrast with results from meta-analysis mentioned above, where the supplementation with prebiotics was significantly associated to a higher weight gain [80].

In the last years there is a growing interest in the simultaneous administration of prebiotics and probiotics, what is termed “symbiotic.” There are a few recent studies which have assessed the effect of symbiotic supplementation on the infant health. The ESPGHAN Committee on Nutrition showed an increase in stool frequency for three types of symbiotic (B. longum BL999 plus GOS/FOS, B. longum BL999 plus L. rhamnosus LPR plus GOS/FOS, and L. paracasei subsp. paracasei plus B. animalis subsp. lactis plus GOS) [79]. Also, Ringel-Kulka et al. showed that a yogurt with the probiotic bacteria Bifidobacterium animalis subspecies lactis (BB-12) and the prebiotic inulin significantly reduced days of fever, improved social and school functioning, and increased frequency of bowel movements in healthy children attending child care centers [85]. Regarding to obesity interventions with symbiotic, Safavi et al. [86] found that treatment of overweight children with a symbiotic mixture of the prebiotic, FOS, in combination with seven probiotic strains was associated with a decreased BMI z-score compared to placebo.

Studies suggest that pre-, probiotic, and symbiotic supplementation may be beneficial in the prevention and management of disease where the gut microbiota has a key role (e.g., necrotizing enterocolitis, gastroenteritis, or obesity). Although these studies show promising beneficial effects, the long-term risks or health benefits of pre- and probiotic supplementation are not clear as results from single studies need to be replicated in well-defined RCTs. Nonetheless, there is active research on functional food that contains pre-, probiotics, and symbiotics supplementation because they can influence not only the microbiota favoring the growth of beneficial microorganisms, but also the mucosal immune system associated to the gut [87].


5. Childhood exposure to antibiotics

Exposure to antibiotics during infancy and childhood use to begin very early. Two different studies showed that >30% of women with a delivery had done systemic antibiotic treatments during pregnancy [88, 89]. Although the effects of antibiotic exposure during pregnancy on acquisition of infants’ microbiota have not been established, maternal antibiotic exposure is relevant since infants’ microbiota is taken at least in part from their mothers. In addition, prenatal antibiotic exposure has been shown to have effects on the birth weight of neonates and is associated with increased risk of obesity and related metabolic sequelae later in life [90, 91].

After birth, a number of neonates, particularly premature infants, receive antibiotics to prevent or treat bacterial infections. Fjalstad et al. showed that 2.3% of all live-born term infants received intravenous antibiotics in the population, they analyzed from 2009 to 2011 [92]. Higher prescription rates were shown in preterm or term infants with relevant clinical problems. In a study involving neonates admitted to the neonatal intensive care unit in U.S. from 2005 to 2010, more than 88% of extremely low birth weight infants were administrated antibiotics [93].

Over the last decade, several national and international health institutions have made an enormous effort to decrease antibiotic use in the pediatric population by educating parents about the futility of treating viral infections with antibiotics and about concerns of antibiotic resistance [94, 95]. But, despite a recent reduction, widespread antibiotic use in infants and children remains a relevant health problem in the entire industrialized world, mainly because most prescriptions were frequently inappropriate [96].

However, even in countries in which the prescribing pattern usually adheres to national guidelines with respect to the choice of antibiotics, antibiotics are still largely prescribed to children, particularly to very young children [97100].

In addition to antibiotic exposure for infection prevention and therapy, children could potentially be substantially exposed to antibiotics through the food supply chain or, more rarely, drinking water [101].

5.1. Evidence from animals

In last 50 years, farmers have been using low doses of antibiotics to promote growth and feed efficiency of pigs, cows, sheep, and poultry [102]. Different antibiotics have been demonstrated to have these effects independently of its class, chemical structure, and mode of action and spectrum of activity. Moreover, the effects on growth are greater when animals receive antibiotics early in life than if the exposure occurs later in life [103105].

Also, studies in mice using multiple types of antibiotics have further confirmed this association, as well as identifying early life as the key period for microbe-mediated programing of host metabolism [106, 107].

Experiments with germ-free animal models have provided direct evidence of the key role of the microbiota in the association between low doses of antibiotics exposure and growth promotion. In 1963, Coates et al. showed that in germ-free chicken antibiotics alone have no growth promoting effects [108]. Recently, Cox et al. showed that germ-free mice who received the microbiota from mice treated with low dose penicillin gained more weight and fat mass than mice colonized with microbiota from control animals [107].

Then, there are two main findings from these experiments. First, early life is a critical time for metabolic development of the host, and second, the microbiome has a key role in this process and its disturbance duty to antibiotic exposure at this time affects the course of growth and development [109].

5.2. Epidemiologic evidence

There is epidemiologic evidence that exposure to antibiotics in early life is associated with increased risk of excess adiposity. Recently, epidemiological studies have shown that this phenomenon can also occur in humans starting in the fetal stage of life. In that sense, Mueller et al. observed in a U.S. cohort that the administration of antibiotics to women in the last two trimesters of pregnancy increased 84% the risk of obesity in children at 7 years old compared to children born to mothers without antibiotics administration at the same period [110]. Also, Mor et al. observed similar results in a study performed in Denmark where they showed that prenatal exposure to systemic antibacterials was associated with an increased risk of overweight and obesity at school age, and this association varies by birth weight [111].

After birth, the exposure to antibiotics has been associated to obesity due to the analysis of different human cohorts in various countries. In a Danish mother-child pairs cohort, Ajslev et al. showed antibiotic exposure in children during the first 6 months was associated with an increased risk of being overweight at 7 years of age; the effect was stronger in boys than in girls. In a U.K. cohort, Trasande et al. showed that antibiotic use in the first 6 months of life was associated with increased BMI at 10, 20, and 38 months of age [19]. Both studies also determined that maternal BMI was a contributing factor for the development of obesity following exposure to antibiotics in early life, with increased effects seen in children with mothers of normal weight compared with children from mothers who were overweight. Also, Azad et al. in a study of Canadian infants showed that antibiotics administered in the first year of life increased the likelihood of a child being overweight at 9 years and 12 years of age being almost seen in boys [112], which was consistent with the previous results from Ajslev et al. In a U.S. cohort, Bailey at al. observed that repeated exposure to broad-spectrum antibiotics at ages 0–23 months was associated with early childhood obesity. Importantly, this observation was associated with the use of broad-spectrum antibiotics, but not with the use of narrow-spectrum antibiotics.

Finally, in a multicenter, multicountry, cross-sectional study (The International Study of Asthma and Allergies in Childhood Phase III) Murphy et al. observed a significant interaction between sex and early-life antibiotic exposure. Exposure to antibiotics during the first 12 months of life was associated with a small increase in BMI in boys aged 5–8 years but not in girls in this large international cross-sectional survey.

Colonization of neonate’s gut microbiota relies on vertical transmission from the mother at the time of delivery; thus, during pregnancy or early-life exposure to antibiotics could have effects on weight later in life by disturbing the proper establishment of the gut microbiota.

5.3. Antibiotic exposure and dysbiosis in children

Prospective studies have showed that changes in gut microbiota in early life may precede the development of overweight and obesity [113, 114].

In particular, some bacterial taxa has been associated with the risk of obesity development, regarding to this, a high abundance of intestinal Bifidobacteria in early life appears to be associated with lower risk of overweight [114, 115], whereas high amounts of Bacteroides fragilis increase the risk of obesity development [113]. Thus, likely factors that exert an impact on gut microbiota composition and functionality in early life may also modulate the risk of obesity development.

Therefore, antibiotic exposure during childhood can reduce the phylogenetic diversity and microbial load of the gut microbiota [116].

Regarding preterm infants it has been shown that treatment with amoxicillin and gentamicin during the first week of life reduced the bacterial diversity and raised the relative abundance of Enterobacter in the second and third weeks of life compared to preterm infants not exposed to antibiotics [117].

Moreover, administration of penicillin, ampicillin, cephalexin, gentamicin, amikacin, erythromycin, vancomycin, clindamycin, and teichomycin to preterm infants has been associated with a decrease in the relative abundance of Bifidobacteriaceae, bacilli, and Lactobacillales spp., commonly linked with a healthy status and an increase in the presence of potentially pathogenic Enterobacteriaceae [117119]. Besides short-term-effects, the dysbiosis produced by antibiotics administration in infants may produce long-term effects like the persistence of the risk of obesity development. It has been observed that 3 months after of antibiotics persists the microbiota disruption [120]. However, antibiotic administration to neonates has been linked to several critical clinical conditions in which modification of the microbiota composition is thought to play a relevant role, in diseases such as necrotizing enterocolitis and sepsis [121, 122].

Antibiotic treatments in early life can lead to long-term alterations in microbiota composition that result in changes to host metabolic functions, particularly during development, increasing the risk of obesity [109].


  1. 1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013. Lancet (London, England). 2014;384(9945):766–781.
  2. 2. Ogburn PL. Obesity and gestational diabetes in pregnancy: an evolving epidemic. Journal of Perinatal Medicine. 2016;44(4):361–362.
  3. 3. Malhotra N, Sharma E, Malhotra J, Bora NM. Obesity in obstetric intensive care patient. Principles of Critical Care in Obstetrics Part IV: Springer; 2016. pp. 317–321.
  4. 4. Spreadbury I. Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2012;5:175–189.
  5. 5. Hollopeter G, Erickson J, Palmiter R. Role of neuropeptide Y in diet-, chemical-and genetic-induced obesity of mice. International Journal of Obesity. 1998;22(6):506–512.
  6. 6. Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Medicine. 2013;11(1):1.
  7. 7. Marchesi JR, Adams DH, Fava F, Hermes GDA, Hirschfield GM, Hold G, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2015:gutjnl-2015-309990.
  8. 8. Sekirov I, Russell SL, Antunes LCM, Finlay BB. Gut microbiota in health and disease. Physiological Reviews. 2010;90(3):859–904.
  9. 9. D’Argenio V, Salvatore F. The role of the gut microbiome in the healthy adult status. Clinica Chimica Acta. 2015;451:97–102.
  10. 10. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World Journal of Gastroenterology: WJG. 2015;21(29):8787.
  11. 11. Fraher MH, O'Toole PW, Quigley EMM. Techniques used to characterize the gut microbiota: a guide for the clinician. Nature Reviews Gastroenterology and Hepatology. 2012;9(6):312–322.
  12. 12. Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host & Microbe. 2008;3(4):213–223.
  13. 13. Tagliabue A, Elli M. The role of gut microbiota in human obesity: recent findings and future perspectives. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD. 2013;23(3):160–168.
  14. 14. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022–1023.
  15. 15. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(31):11070–11075.
  16. 16. Collado MC, Cernada M, Neu J, Pérez-Martínez G, Gormaz M, Vento M. Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants. Pediatric Research. 2015;77(6):726–731.
  17. 17. Track NS. The gastrointestinal endocrine system. Canadian Medical Association Journal. 1980;122(3):287.
  18. 18. Cerdó T, García-Valdés L, Altmäe S, Ruíz-Rodríguez A, Suárez A, Campoy C. Role of microbiota function during early life and children neurodevelopment Aricule in press. Trends in Food Science & Technology xxx (2016); 1–16.
  19. 19. Trasande L, Blustein J, Liu M, Corwin E, Cox L, Blaser M. Infant antibiotic exposures and early-life body mass. International Journal of Obesity. 2013;37(1):16–23.
  20. 20. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences. 2010;107(26):11971–11975.
  21. 21. Murphy EF, Cotter PD, Hogan A, O'Sullivan O, Joyce A, Fouhy F, et al. Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut. 2013;62(2):220–226.
  22. 22. DiPietro JA. Maternal stress in pregnancy: considerations for fetal development. Journal of Adolescent Health. 2012;51(2):S3–S8.
  23. 23. Kaiser L, Allen LH. Position of the American Dietetic Association: nutrition and lifestyle for a healthy pregnancy outcome. Journal of the American Dietetic Association. 2008;108(3):553–561.
  24. 24. Gardiner PM, Nelson L, Shellhaas CS, Dunlop AL, Long R, Andrist S, et al. The clinical content of preconception care: nutrition and dietary supplements. American Journal of Obstetrics and Gynecology. 2008;199(6):S345–S56.
  25. 25. Temel S, van Voorst SF, Jack BW, Denktaş S, Steegers EA. Evidence-based preconceptional lifestyle interventions. Epidemiologic Reviews. 2014;36(1):19–30.
  26. 26. Lain KY, Catalano PM. Metabolic changes in pregnancy. Clinical Obstetrics and Gynecology. 2007;50(4):938–948.
  27. 27. De Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Australian and New Zealand Journal of Obstetrics and Gynaecology. 2006;46(1):4–14.
  28. 28. Leddy MA, Power ML, Schulkin J. The impact of maternal obesity on maternal and fetal health. Reviews in Obstetrics and Gynecology. 2008;1(4):170–178.
  29. 29. Galley JD, Bailey M, Dush CK, Schoppe-Sullivan S, Christian LM. Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS One. 2014;9(11):e113026.
  30. 30. Chu SY, Kim SY, Lau J, Schmid CH, Dietz PM, Callaghan WM, et al. Maternal obesity and risk of stillbirth: a metaanalysis. American Journal of Obstetrics and Gynecology. 2007;197(3):223–238.
  31. 31. Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. The American Journal of Clinical Nutrition. 2008;88(4):894–899.
  32. 32. Gritz EC, Bhandari V. The human neonatal gut microbiome: a brief review. Frontiers in Pediatrics. 2015;3:17.
  33. 33. Mueller NT, Shin H, Pizoni A, Werlang IC, Matte U, Goldani MZ, et al. Birth mode-dependent association between pre-pregnancy maternal weight status and the neonatal intestinal microbiome. Scientific Reports. 2016;6.
  34. 34. Smith K, McCoy KD, Macpherson AJ, editors. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Seminars in Immunology: Elsevier; April 2007;19(2):59–69.
  35. 35. DiGiulio DB, Gervasi M, Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, et al. Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. Journal of Perinatal Medicine. 2010;38(5):503–513.
  36. 36. Lee SE, Romero R, Lee SM, Yoon BH. Amniotic fluid volume in intra-amniotic inflammation with and without culture-proven amniotic fluid infection in preterm premature rupture of membranes. Journal of Perinatal Medicine. 2010;38(1):39–44.
  37. 37. Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Bieda J, et al. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome. 2014;2(1):1.
  38. 38. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Science Translational Medicine. 2014;6(237):237ra65-ra65.
  39. 39. Amarasekara R, Jayasekara RW, Senanayake H, Dissanayake VH. Microbiome of the placenta in pre‐eclampsia supports the role of bacteria in the multifactorial cause of pre‐eclampsia. Journal of Obstetrics and Gynaecology Research. 2015;41(5):662–669.
  40. 40. Antony KM, Ma J, Mitchell KB, Racusin DA, Versalovic J, Aagaard K. The preterm placental microbiome varies in association with excess maternal gestational weight gain. American Journal of Obstetrics and Gynecology. 2015;212(5):653. e1-e16.
  41. 41. Moles L, Gomez M, Heilig H, Bustos G, Fuentes S, de Vos W, et al. Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One. 2013;8(6):e66986.
  42. 42. Hu J, Nomura Y, Bashir A, Fernandez-Hernandez H, Itzkowitz S, Pei Z, et al. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS One. 2013;8(11):e78257.
  43. 43. Martin R, Makino H, Yavuz AC, Ben-Amor K, Roelofs M, Ishikawa E, et al. Early-life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota. PLoS One. 2016;11(6):e0158498.
  44. 44. Kuhle S, Tong O, Woolcott C. Association between caesarean section and childhood obesity: a systematic review and meta‐analysis. Obesity Reviews. 2015;16(4):295–303.
  45. 45. Blustein J, Attina T, Liu M, Ryan A, Cox L, Blaser M, et al. Association of caesarean delivery with child adiposity from age 6 weeks to 15 years. International Journal of Obesity. 2013;37(7):900–906.
  46. 46. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Medicine. 2016;22: 250–253.
  47. 47. Dogra S, Sakwinska O, Soh S-E, Ngom-Bru C, Brück WM, Berger B, et al. Rate of establishing the gut microbiota in infancy has consequences for future health. Gut Microbes. 2015;6(5):321–325.
  48. 48. Fouhy F, Ross RP, Fitzgerald GF, Stanton C, Cotter PD. Composition of the early intestinal microbiota: knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes. 2012;3(3):203–220.
  49. 49. Bäckhed F. Programming of host metabolism by the gut microbiota. Annals of Nutrition and Metabolism. 2011;58(Suppl. 2):44–52.
  50. 50. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science (New York, NY). 2005;308(5728):1635–1638.
  51. 51. Nylund L, Satokari R, Salminen S, de Vos WM. Intestinal microbiota during early life - impact on health and disease. The Proceedings of the Nutrition Society. 2014;73(4):457–469.
  52. 52. Timby N, Domellöf E, Hernell O, Lönnerdal B, Domellöf M. Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial. The American Journal of Clinical Nutrition. 2014;99(4):860–868.
  53. 53. Kramer MS, Kakuma R. The optimal duration of exclusive breastfeeding. Protecting Infants through Human Milk: Springer; 2004. Section II, pp. 63–77.
  54. 54. World Health O, Unicef. Global strategy for infant and young child feeding: World Health Organization; 2003.
  55. 55. Le Huërou-Luron I, Blat S, Boudry G. Breast- v. formula-feeding: impacts on the digestive tract and immediate and long-term health effects. Nutrition Research Reviews. 2010;23(01):23–36.
  56. 56. Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatric Clinics of North America. 2013;60(1):49–74.
  57. 57. Kulski JK, Hartmann PE. Changes in human milk composition during the initiation of lactation. The Australian Journal of Experimental Biology and Medical Science. 1981;59(1):101–114.
  58. 58. Field CJ. The immunological components of human milk and their effect on immune development in infants. The Journal of Nutrition. 2005;135(1):1–4.
  59. 59. Castellote C, Casillas R, Ramírez-Santana C, Pérez-Cano FJ, Castell M, Moretones MG, et al. Premature delivery influences the immunological composition of colostrum and transitional and mature human milk. The Journal of Nutrition. 2011;141(6):1181–1187.
  60. 60. Turroni F, Peano C, Pass DA, Foroni E, Severgnini M, Claesson MJ, et al. Diversity of bifidobacteria within the infant gut microbiota. PLoS One. 2012;7(5):e36957.
  61. 61. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. Journal of Pediatric Gastroenterology and Nutrition. 2000;30(1):61–67.
  62. 62. Jost T, Lacroix C, Braegger CP, Chassard C. New insights in gut microbiota establishment in healthy breast fed neonates. PLoS One. 2012;7(8):e44595.
  63. 63. Jost T, Lacroix C, Braegger CP, Rochat F, Chassard C. Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environmental Microbiology. 2014;16(9):2891–2904.
  64. 64. Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. The American Journal of Clinical Nutrition. 2012;96(3):544–551.
  65. 65. Gueimonde M, Laitinen K, Salminen S, Isolauri E. Breast milk: a source of bifidobacteria for infant gut development and maturation? Neonatology. 2007;92(1):64–66.
  66. 66. Fallani M, Young D, Scott J, Norin E, Amarri S, Adam R, et al. Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics. Journal of Pediatric Gastroenterology and Nutrition. 2010;51(1):77–84.
  67. 67. Bezirtzoglou E, Tsiotsias A, Welling GW. Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe. 2011;17(6):478–482.
  68. 68. Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatrica (Oslo, Norway: 1992). 2009;98(2):229–938.
  69. 69. Favier CF, Vaughan EE, De Vos WM, Akkermans AD. Molecular monitoring of succession of bacterial communities in human neonates. Applied and Environmental Microbiology. 2002;68(1):219–226.
  70. 70. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutrition Workshop Series Paediatric Programme. 2008;62:205–218.
  71. 71. Sanders ME. Probiotics: definition, sources, selection, and uses. Clinical Infectious Diseases. 2008;46(Suppl. 2):S58–S61.
  72. 72. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology. 2014;11(8):506–514.
  73. 73. Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentability of human milk oligosaccharides by several strains of bifidobacteria. Molecular Nutrition & Food Research. 2007;51(11):1398–1405.
  74. 74. Sela DA, Mills DA. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends in Microbiology. 2010;18(7):298–307.
  75. 75. Yu ZT, Chen C, Kling DE, Liu B, McCoy JM, Merighi M, et al. The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota. Glycobiology. 2013;23(2):169–177.
  76. 76. Marcobal A, Sonnenburg JL. Human milk oligosaccharide consumption by intestinal microbiota. Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2012;18 (Suppl. 4):12–15.
  77. 77. Food ESCo. Additional statement on the use of resistant short chain carbohydrates (oligofurctosyl-saccharose and oligogalactosyl-lactose) in infant formula and in follow-on formula. EC Scientific Committee on Food; Brussels, Belgium. 2001.
  78. 78. Rao S, Srinivasjois R, Patole S. Prebiotic supplementation in full-term neonates: a systematic review of randomized controlled trials. Archives of Pediatrics & Adolescent Medicine. 2009;163(8):755–764.
  79. 79. Braegger C, Chmielewska A, Decsi T, Kolacek S, Mihatsch W, Moreno L, et al. Supplementation of infant formula with probiotics and/or prebiotics: a systematic review and comment by the ESPGHAN committee on nutrition. Journal of Pediatric Gastroenterology and Nutrition. 2011;52(2):238–250.
  80. 80. Koleva PT, Bridgman SL, Kozyrskyj AL. The infant gut microbiome: evidence for obesity risk and dietary intervention. Nutrients. 2015;7(4):2237–2260.
  81. 81. Mugambi MN, Musekiwa A, Lombard M, Young T, Blaauw R. Synbiotics, probiotics or prebiotics in infant formula for full term infants: a systematic review. Nutrition Journal. 2012;11(1):1.
  82. 82. Lyon M, Wood S, Pelletier X, Donazzolo Y, Gahler R, Bellisle F. Effects of a 3-month supplementation with a novel soluble highly viscous polysaccharide on anthropometry and blood lipids in nondieting overweight or obese adults. Journal of Human Nutrition and Dietetics: The Official Journal of the British Dietetic Association. 2011;24(4):351–359.
  83. 83. Parnell JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. The American Journal of Clinical Nutrition. 2009;89(6):1751–1759.
  84. 84. Yang HY, Yang SC, Chao JC, Chen JR. Beneficial effects of catechin-rich green tea and inulin on the body composition of overweight adults. The British Journal of Nutrition. 2012;107(5):749–754.
  85. 85. Ringel-Kulka T, Kotch JB, Jensen ET, Savage E, Weber DJ. Randomized, double-blind, placebo-controlled study of synbiotic yogurt effect on the health of children. The Journal of Pediatrics. 2015;166(6):1475–81. e3.
  86. 86. Safavi M, Farajian S, Kelishadi R, Mirlohi M, Hashemipour M. The effects of synbiotic supplementation on some cardio-metabolic risk factors in overweight and obese children: a randomized triple-masked controlled trial. International Journal of Food Sciences and Nutrition. 2013;64(6):687–693.
  87. 87. Latulippe ME, Meheust A, Augustin L, Benton D, Berčík P, Birkett A, et al. ILSI Brazil International Workshop on Functional Foods: a narrative review of the scientific evidence in the area of carbohydrates, microbiome, and health. Food & Nutrition Research. 2013;57.
  88. 88. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B streptococcal disease: Revised guidelines from CDC, 2010: Department of Health and Human Services, Centers for Disease Control and Prevention; 2010.
  89. 89. Broe A, Pottegard A, Lamont RF, Jorgensen JS, Damkier P. Increasing use of antibiotics in pregnancy during the period 2000–2010: prevalence, timing, category, and demographics. BJOG: An International Journal of Obstetrics and Gynaecology. 2014;121(8):988–996.
  90. 90. Vidal AC, Murphy SK, Murtha AP, Schildkraut JM, Soubry A, Huang Z, et al. Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring. International Journal of Obesity. 2013;37(7):907–913.
  91. 91. Jepsen P, Skriver MV, Floyd A, Lipworth L, Schønheyder HC, Sørensen HT. A population‐based study of maternal use of amoxicillin and pregnancy outcome in Denmark. British Journal of Clinical Pharmacology. 2003;55(2):216–621.
  92. 92. Fjalstad JW, Stensvold HJ, Bergseng H, Simonsen GS, Salvesen B, Rønnestad AE, et al. Early-onset sepsis and antibiotic exposure in term infants: a nationwide population-based study in Norway. The Pediatric Infectious Disease Journal. 2016;35(1):1–6.
  93. 93. Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK, Smith PB. Medication use in the neonatal intensive care unit. American Journal of Perinatology. 2014;31(09):811–822.
  94. 94. Lieberman JM. Appropriate antibiotic use and why it is important: the challenges of bacterial resistance. The Pediatric Infectious Disease Journal. 2003;22(12):1143–1151.
  95. 95. Besser RE. Antimicrobial prescribing in the United States: good news, bad news. Annals of Internal Medicine. 2003;138(7):605–606.
  96. 96. Hersh AL, Jackson MA, Hicks LA, Brady MT, Byington CL, Davies HD, et al. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics. 2013;132(6):1146–1154.
  97. 97. Pottegård A, Broe A, Aabenhus R, Bjerrum L, Hallas J, Damkier P. Use of antibiotics in children: a Danish nationwide drug utilization study. The Pediatric Infectious Disease Journal. 2015;34(2):e16-e22.
  98. 98. Holstiege J, Garbe E. Systemic antibiotic use among children and adolescents in Germany: a population-based study. European Journal of Pediatrics. 2013;172(6):787–795.
  99. 99. Blix HS, Engeland A, Litleskare I, Rønning M. Age-and gender-specific antibacterial prescribing in Norway. Journal of Antimicrobial Chemotherapy. 2007;59(5):971–976.
  100. 100. Schneider-Lindner V, Quach C, Hanley JA, Suissa S. Secular trends of antibacterial prescribing in UK paediatric primary care. Journal of Antimicrobial Chemotherapy. 2011;66(2):424–433.
  101. 101. Martin MJ, Thottathil SE, Newman TB. Antibiotics overuse in animal agriculture: a call to action for health care providers. American Journal of Public Health. 2015;105(12):2409–2410.
  102. 102. Jukes TH, Williams WL. Nutritional effects of antibiotics. Pharmacological Reviews. 1953;5(4):381–420.
  103. 103. Gaskins HR, Collier CT, Anderson DB. Antibiotics as growth promotants: mode of action. Animal Biotechnology. 2002;13(1):29–42.
  104. 104. Butaye P, Devriese LA, Haesebrouck F. Antimicrobial growth promoters used in animal feed: effects of less well known antibiotics on gram-positive bacteria. Clinical Microbiology Reviews. 2003;16(2):175–188.
  105. 105. Muir LA. Mode of action of exogenous substances on animal growth—an overview. Journal of Animal Science. 1985;61(Suppl. 2):154–180.
  106. 106. Cho I, Yamanishi S, Cox L, Methé BA, Zavadil J, Li K, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488(7413):621–626.
  107. 107. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158(4):705–721.
  108. 108. Coates ME, Fuller R, Harrison GF, Lev M, Suffolk SF. A comparision of the growth of chicks in the Gustafsson germ-free apparatus and in a conventional environment, with and without dietary supplements of penicillin. British Journal of Nutrition. 1963;17(01):141–150.
  109. 109. Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nature Reviews Endocrinology. 2015;11(3):182–190.
  110. 110. Mueller NT, Whyatt R, Hoepner L, Oberfield S, Dominguez-Bello MG, Widen EM, et al. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. International Journal of Obesity. 2015;39:665–670.
  111. 111. Mor A, Antonsen S, Kahlert J, Holsteen V, Jørgensen S, Holm-Pedersen J, et al. Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study. International Journal of Obesity. 2015;39(10):1450–1455.
  112. 112. Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. Infant antibiotic exposure and the development of childhood overweight and central adiposity. International Journal of Obesity. 2014;38(10):1290–1298.
  113. 113. Vael C, Verhulst SL, Nelen V, Goossens H, Desager KN. Intestinal microflora and body mass index during the first three years of life: an observational study. Gut Pathogens. 2011;3(1):8.
  114. 114. Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. The American Journal of Clinical Nutrition. 2008;87(3):534–538.
  115. 115. Dogra S, Sakwinska O, Soh SE, Ngom-Bru C, Bruck WM, Berger B, et al. Dynamics of infant gut microbiota are influenced by delivery mode and gestational duration and are associated with subsequent adiposity. mBio. 2015;6(1).
  116. 116. Principi N, Esposito S. Antibiotic administration and the development of obesity in children. International Journal of Antimicrobial Agents. 2016;47(3):171–177.
  117. 117. Greenwood C, Morrow AL, Lagomarcino AJ, Altaye M, Taft DH, Yu Z, et al. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. The Journal of Pediatrics. 2014;165(1):23–29.
  118. 118. Tanaka S, Kobayashi T, Songjinda P, Tateyama A, Tsubouchi M, Kiyohara C, et al. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunology & Medical Microbiology. 2009;56(1):80–87.
  119. 119. Arboleya S, Sánchez B, Milani C, Duranti S, Solís G, Fernández N, et al. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. The Journal of Pediatrics. 2015;166(3):538–544.
  120. 120. Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host & Microbe. 2015;17(5):553–564.
  121. 121. Leach ST, Lui K, Naing Z, Dowd SE, Mitchell HM, Day AS. Multiple opportunistic pathogens, but not pre-existing inflammation, may be associated with necrotizing enterocolitis. Digestive Diseases and Sciences. 2015;60(12):3728–3734.
  122. 122. Berrington JE, Stewart CJ, Cummings SP, Embleton ND. The neonatal bowel microbiome in health and infection. Current Opinion in Infectious Diseases. 2014;27(3):236–243.

Written By

Tomás Cerdó, Alicia Ruiz and Cristina Campoy

Submitted: 17 May 2016 Reviewed: 22 September 2016 Published: 22 March 2017