Next Article in Journal
Turkish Version of the New Instrument for Orthorexia Nervosa—Test of Orthorexia Nervosa (TON-17): A Validity and Reliability Study
Next Article in Special Issue
Untargeted Metabolomic Analysis of Lactation-Stage-Matched Human and Bovine Milk Samples at 2 Weeks Postnatal
Previous Article in Journal
Gestational Weight Gain Relates to DNA Methylation in Umbilical Cord, Which, In Turn, Associates with Offspring Obesity-Related Parameters
Previous Article in Special Issue
Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 15
Issue 14
10.3390/nu15143177
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Antimicrobial Resistance Genes (ARGs), the Gut Microbiome, and Infant Nutrition

by
Rufus J. Theophilus
and
Diana Hazard Taft
*
Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA
*
Author to whom correspondence should be addressed.
Nutrients 2023, 15(14), 3177; https://doi.org/10.3390/nu15143177
Submission received: 29 June 2023 / Revised: 14 July 2023 / Accepted: 14 July 2023 / Published: 18 July 2023
(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)
Browse Figure
Versions Notes

Abstract

:
The spread of antimicrobial resistance genes (ARGs) is a major public health crisis, with the ongoing spread of ARGs leading to reduced efficacy of antibiotic treatments. The gut microbiome is a key reservoir for ARGs, and because diet shapes the gut microbiome, diet also has the potential to shape the resistome. This diet–gut microbiome–resistome relationship may also be important in infants and young children. This narrative review examines what is known about the interaction between the infant gut microbiome, the infant resistome, and infant nutrition, including exploring the potential of diet to mitigate infant ARG carriage. While more research is needed, diet has the potential to reduce infant and toddler carriage of ARGs, an important goal as part of maintaining the efficacy of available antibiotics and preserving infant and toddler health.

Graphical Abstract

1. Introduction

Antimicrobial resistance (AMR) constitutes a major global health crisis. In 2019, about 5 million deaths worldwide were associated with AMR [1], with approximately 35,000 deaths in the United States [2]. The number of resistant infections was even higher, with more than 2.8 million resistant infections occurring in the US annually [3]. The cost of these infections is high, surpassing USD 55 billion in the US, including USD 20 billion in direct health care costs and USD 35 billion in loss of productivity [2]. Approximately USD 4.6 billion of the direct health care costs related to AMR comes from treating just the six most common multidrug-resistant infections [4]. While people of all ages can develop multidrug-resistant infections, infants are particularly vulnerable because use of some antibiotics is contradicted in young children and because overuse and misuse of antibiotics are common in children [5]. AMR infections in infants can have fatal consequences, with an estimated 214,000 neonates dying from AMR-linked sepsis every year [6]. By country, India loses over 56,000 newborns to AMR infections annually, Pakistan loses over 25,000 newborns to AMR infections each year, and Nigeria loses approximately 19,400 newborns to AMR infections annually [6]. Major risk factors for AMR infections in humans of all ages include chronic diseases, surgery, and the use of antibiotics [7]. Many of these risk factors occur less frequently in infants, with the exception of antibiotic use [8,9,10,11]. Infants are commonly exposed to antibiotics both indirectly (e.g., maternal antibiotic exposure during pregnancy [12,13] or at delivery [14]) and directly to treat infections. Antibiotics are routinely and frequently given during infancy [15,16], and their abuse, misuse, or improper prescription lead to AMR infection proliferation [17]. AMR infections caused by pathogens previously susceptible to an antibiotic occur because bacteria are capable of acquiring antimicrobial resistance genes (ARGs), and these ARGs act by a wide variety of mechanisms [18]. There are a wide variety of ARGs currently known to science, and nearly all antibiotics have known ARGs [19].
There are multiple means by which a pathogen can become resistant to an antibiotic. Least concerning are pathogens that are innately resistant to some antibiotics, for example, Pseudomonas aeruginosa is intrinsically resistant to a number of different antibiotics [18]. In some cases of greater concern, pathogens become resistant after exposure to antibiotics by acquiring point mutations in chromosomal genes, as has occurred in some Salmonella enterica strains [20]. Most concerning to public health is the ability of bacteria to acquire ARGs through horizontal gene transfer (HGT), as HGT enables the rapid evolution and spread of multidrug-resistant bacteria [21,22]. The ability of ARGs to spread by HGT complicates approaches to controlling the spread of AMR infections. HGT of plasmids and transposons permits ARGs to be shared between diverse species, especially when communities of microbes are exposed to antibiotics [23]. Bacteria with ARGs on transferable genetic elements are found in many microbial communities, including human-associated communities, and myriads of animal-associated communities [24].
ARGs are identified using a variety of techniques. Traditional methods are frequently based on bacterial culture and rely on phenotype testing to find the minimal inhibitor concentration (MIC) of antibiotics [25]. Initial identification of ARGs was completed through painstaking identification of enzymes and Sanger sequencing [26,27]. This work led to PCR- and microarray-based tests for specific ARGs [28,29]. The decreasing cost of whole-genome sequencing and whole-metagenome sequencing in combination with databases of antimicrobial resistance genes made it feasible to identify ARGs from sequencing data [30,31]. These sequencing technologies enabled the unbiased study of ARGs in microbial communities without specifically testing for selected, individual ARGs [32]. The growing number of methods available for identification of ARGs are enabling discoveries of novel ARGs and a better understanding of the ARGs in complete environmental communities [33].
The ubiquity of transferable ARGs and the improvements in our ability to track and find ARGs have given rise to the One Health concept as applied to ARGs [34,35]. According to the WHO, the One Health perspective takes an integrated, unifying approach to sustainably balance and optimize the health of humans, animals, plants, and the environment/ecosystems [36]. The goal of One Health is to help to coordinate research efforts in various fields to address global health-related challenges (such as AMR) that affect humans, animals, and their environments [37]. The complexity of AMR warrants the all-discipline and all-encompassing framework of One Health [38,39]. One Health has played a pivotal role in combatting the rise of AMR through its global advocacy and interventions [34], including interventions aimed at protecting the health of infants and young children [40]. As an example of successful One Health program to reduce child mortality, the WHO has updated its yaws eradication strategy to balance the risk of increasing azithromycin resistance with the need to protect human health from bacterial diseases [41].
The One Health perspective that multiple ecosystems must be considered to fully understand AMR does not mean that all ARGs are equal threats to public health. Zhang et al. have developed a framework to describe the threat posed to ARGs by human health [42]. In this framework, the highest-risk ARGs are those that are on mobile genetic elements, are enriched in human-associated environments, and are known to occur in high-risk pathogens [42]. Because of the importance of human-associated environments to the risk levels of ARGs, consideration of the ARGs in the gut microbiome is particularly important. The gut microbiome is defined as the assemblage of commensals, symbionts, and pathogens that inhabit the human gut [43]. The gut microbiome contains the gut resistome, defined as the collection of all ARGs contained within the gut microbiome [44]. This means that the gut serves as a repository of ARGs, with healthy individuals carrying a number of AMR organisms [45]. As the human gut microbiome is by definition a human-associated environment, this suggests that the gut resistome may be of particular importance to understanding the threat posed by ARGs to human health. This makes it critical to understand the factors that shape the human gut resistome.

2. Diet, Age, and Antimicrobial Resistance Gene Carriage

Diet is a major driver of the gut microbiome composition, with different diets eliciting changes in gut microbiome composition [46]. Diet also changes the metabolites produced by the gut microbiome, with marked differences in the metabolome of vegans and omnivores [47]. Dietary fiber is particularly important in influencing the metabolites produced by the gut microbiome [48]. Because the gut microbiome serves as a reservoir for ARGs and because diet helps to shape the gut microbiome, dietary changes have the potential to alter the resistome. One recent study that evaluated the association of diet and antimicrobial resistance in healthy US adults demonstrated that adults who consume diets higher in fiber carry lower levels of ARGs [49]. It remains unknown if deliberate dietary interventions in adults can alter ARG carriage; but the work by Oliver et al. does suggest that increased fiber intake might result in lower ARG levels [49] and that future work on the relationship between diet and the resistome is warranted.
Use of antibiotics in agriculture drives the proliferation of ARGs [50]. Antimicrobial agents are primarily used in animal agriculture but are used at lower levels when farming plants [51]. Because of the large quantity of antimicrobial agents used during livestock production, reduction in antibiotic use in livestock production is currently a priority to protect both human and livestock health [52]. Consumption of animal products is associated with increased risk of some AMR infections, for example, consumption of poultry is associated with increased risk of multidrug-resistant urinary tract infections in women [53]. Despite this connection between meat consumption and AMR infections, one study that compared omnivorous, vegetarian, and vegan diets did not find a clear connection between diet type and ARG carriage [54], suggesting that a more nuanced understanding of diet than just crude measures of animal product consumption and total plant fiber consumption are needed to understand the associations between diet and the resistome.
Age is important to the gut resistome, as infants carry higher levels of ARGs than their own mothers [55]. As in adults, the composition of the infant gut microbiome is also important to the infant gut resistome, such that infants with higher levels of Bifidobacterium carry lower levels of ARGs [56]. Therefore, this review seeks to summarize what is known about the infant gut resistome, including the potential for diet to alter the resistome in infants. We will briefly highlight the connection between diet and the gut microbiome in young children, continue with a discussion of how infants acquire ARGs (including the role of breastmilk feeding), then consider the same factors during the weaning period, and finally discuss the potential for infants to act as a source of ARGs that then transmit to others.

3. Diet and the Gut Microbiome of Infants (0 to 6 Months)

The WHO and allied agencies recognize how crucial an appropriate diet is to maintain the growth and development of infants; therefore, to support infant health, the WHO recommends exclusive breastfeeding until infants are six months of age [57]. After six months of age, complementary foods should be introduced but the child’s diet should include continued breastfeeding until the child is two years of age or older [57]. Exclusive breastfeeding for the first six months of life is possible because breastmilk is complete nutrition for the infant during this period [58]. Breastmilk also provides infants with antibodies that are protective against infectious diseases and pathogens [59]. Furthermore, other bioactive compounds present in breast milk, including enzymes, immune cells, and antimicrobial peptides provide additional benefits to the infant by helping to reduce risk of infection [60,61].
Diet is a crucial factor affecting the composition of the gut microbiome, especially in infants [62,63]. From the earliest days of microbiome research, scientists described marked differences between the microbes found in the feces of breastfed infants and formula-fed infants [64], and these differences remain in modern infants [65]. One key difference between breast milk and formula is that breastmilk contains human milk oligosaccharides (HMOs) [66], compounds that are abundant in human milk and contribute to the formation and regulation of the infant gut microbiome [66,67]. HMOs are indigestible by infants but instead act as prebiotics supporting the growth of beneficial bacteria, including members of genera Bifidobacterium and Bacteroides [67,68,69,70]. In addition, HMOs function as soluble “decoy receptors”, potentially blocking pathogens from infecting infants [70,71,72]. By promoting the growth of beneficial bacteria and preventing infection with pathogens, HMOs contribute to the development of a healthy and stable gut microbiome [67].
HMOs are particularly important to the infant gut microbiome as they are now known to be what was once referred to as the “bifidogenic factor” of breastmilk [73]. Historically, exclusively breastfed infants had gut microbiomes dominated by Bifidobacterium to the point of being near monocultures, while historically formula-fed (previously referred to as “bottle-fed”) infants had a more diverse microbiome [64]. Today, there is considerable variation in the levels of Bifidobacterium that colonize breastfed infants based on geography, a trend potentially related to differences in historical breastfeeding patterns [74]. As ARGs are not evenly distributed across microbial taxa [75], differences in gut microbiome composition driven by differences in diet have the potential to profoundly influence ARG carriage.

4. Infant Gut Microbiome, ARG Acquisition, and Breastmilk Feeding

Microbial colonization of the infant gut begins at birth [76]. This initial exposure to maternal microbes forms the basis of the infant gut microbiome [77]. During vaginal birth, infants are exposed to various microorganisms from the mother’s vaginal tract and to various fecal microbiota as well as additional microbes from the immediate environment of the delivery room [77]. Infants born by Cesarean section (C-section) are not exposed to maternal vaginal or fecal microbes to the same extent but instead acquire bacteria from maternal skin and the hospital environment leading to a distinct gut microbiome composition by delivery mode [77]. Regardless of delivery mode, infants are exposed to a mixture of antibiotic-sensitive and -resistant bacteria [13,78]. The birth process therefore contributes to the vertical transmission of resistant organisms [79].
Intrapartum antibiotic use may also contribute to the vertical transmission of ARGs at birth. C-section-delivered infants are frequently exposed to intrapartum antibiotics [13,55]. This practice can reduce the risk of infection but also contributes to the selection and proliferation of resistant bacteria in infants and mothers [80]. Intrapartum antibiotic exposure use is not limited to C-section deliveries, as intrapartum antibiotic prophylaxis (IAP) is given to reduce the risk of early-onset sepsis in infants born to Group B Streptococcus-positive mothers [81]. Maternal carriage of Group B Streptococcus is common, leading to antibiotic exposure in 25% of vaginally born US infants [82]. Although this approach is effective in reducing early-onset sepsis, the downside is that it increases ARG levels in infant gut microbiome [13].
After delivery, antibiotic use by infants is common during the first year of life, with 79% of infants in a large Tennessee cohort having at least one antibiotic prescription filled during the first year of life [83]. In Europe, where antibiotic prescription is less common in the first year of life, one study reported that only 39% of European infants received at least one prescription by age 1 year [84]. Studies have found that infants who were given antibiotics early in life had greater abundance of ARGs in their gut microbiome compared to infants who were not exposed to antibiotics [78,85,86,87]. This indicates that in early life, use of antibiotics can disrupt infant gut microbiome, resulting in reduced bacterial diversity and greater carriage of resistant bacteria [78,85,86,87].
Even in the absence of antibiotic exposure, infant acquisition of ARGs does not end with delivery, with the number of different ARGs detected increasing with infant age [88]. Daycares are likely a source of antimicrobial resistance bacteria transmission, as resistant pathogens are known to spread in daycares [89]. While not specifically studied in infants, dogs are known to transmit antimicrobial resistance bacteria to their owners [90], and so household pets are also a potential source of ARGs in infants, especially as households are at least occasionally the source of infections for infants [91]. ARGs may also transmit between other household members. For example, in one study, infants with a twin had a resistome more similar to their twin than to their mothers, and infant gut resistomes were no more similar to their mothers’ gut resistome than to the gut resistome of other unrelated infants [79]. This finding of minimal similarity between the infant and maternal resistome is not consistent in the literature. A different study reported that ARGs are similar between mothers and infants [92] and that there was an overlap in the ARGs present in breastmilk and the ARGs present in the infant gut microbiome [92].
There are other studies where ARGs in the infant gut microbiome appear to be associated with those in breastmilk. For example, one study was able to isolate antimicrobial-resistant Enterococcus faecium from breastmilk [93], while another study reported the isolation of resistant E. faecium and resistant Lactobacillus species from milk [94]. The overlap in ARGs found in breastmilk and the infant gut microbiome is not the full story on the association of breastmilk with the infant resistome because breastmilk feeding was associated with reduced gut carriage of ARGs compared to formula feeding [95]. This relationship may be partially because of the fact that breastmilk feeding supports the growth of infant commensals, such as Bifidobacterium, that are associated with reduced carriage of ARGs [56,95,96]. For infants older than six months of age, breastmilk is no longer adequate for all the infant’s nutritional needs. This necessitates the introduction of solid foods, although breastfeeding remains part of the recommended infant diet until the infant is age two years or older [58], and these dietary changes have the potential to result in a changing relationship between infant diet and the gut resistome.

5. Infant Diet during the Complimentary Feeding Period and the Gut Microbiome (Over 6 Months)

After six months of age, breastmilk is no longer nutritionally complete for infants, as growing babies need more iron and other micronutrients than are provided by breastmilk [97]. Complementary foods should be nutrient dense and should include essential nutrients such as iron, zinc, calcium, vitamins, and a variety of healthy fats to foster healthy growth and development [98]. One important measure of a healthy diet during the complementary feeding period is dietary diversity, with infants showing improved growth with a more diverse diet [99]. Complementary feeding practices vary globally, with US infants less likely to achieve an adequate minimum diet diversity by age 12 months compared to Mexican or Chinese infants [100].
Weaning affects infants physiologically and changes the morphology of the intestine [101,102]. These changes correspond with changes in the gut microbiome that may have long-term impacts on infant health [103]. One of the most important factors that affects the gut microbiome during weaning is the timing of introduction of solid foods. Studies have shown that infants who are introduced to solid foods earlier (e.g., at 4 or 5 months of age) have a different gut microbiome composition than infants who are introduced to solid foods at later time points [104,105]. However, the observed changes have been attributed to duration of exclusive breastfeeding and not the age at which infants are introduced to solids [104,105]. Early introduction of solid foods is associated with a higher abundance of Bacteroides and a lower abundance of bifidobacteria, both of which are important groups of microorganisms that play a role in immunity and metabolism [106,107,108]. The introduction of the first complementary food to infants results in rapid changes to the metabolites produced by the gut microbiome and in changes to the beta-diversity of the infant gut microbiome [109].
The type of solid foods consumed influences the gut microbiome. Data from adults demonstrate that a diet rich in fiber, fruits, and vegetables promotes a diverse and balanced gut microbiome, while processed foods and sugar have been linked to a less diverse and imbalanced gut microbiome [110]. This is because fiber-rich foods and fruits and vegetables act as prebiotics, promoting the growth of beneficial microorganisms in the gut, while processed foods and sugar are pro-inflammatory, promoting harmful microorganisms [111]. In an in vitro system that uses gut microbes collected from infant feces, the sugar composition of fibers in artificially digested foods correlated with changes in the metabolites produced and in the diversity of gut microbes [112], further supporting the connection between dietary fiber consumption, infant gut microbiome composition, and metabolite production. In infants, the introduction of complementary feeding induces significant changes in the gut microbiome, including the replacement of Bifidobacteriacea, Enterobacteriaceae, and Lactobacillaceae with taxa more commonly found in adults, such as Clostridium and Bacteriodes [113].

6. Complementary Feeding Period and ARG Carriage in Infants

Preventing AMR infections is particularly critical during the complementary feeding period, as infants are more vulnerable to infection as they transition away from a breastmilk-only diet [114,115]. This period of life also exhibits marked shifts in the infant resistome, with the diversity of ARGs increasing [104] but their abundance decreasing in the gut microbiome [56]. This decrease in ARG abundance is correlated with the increasing diversity of carbohydrate utilization genes [116], suggesting a potential role for the complementary diet in shaping the resistome in early life. Escherichia contribute the highest abundance of ARGs [116]. The prevalence of resistant Escherichia coli in infants increases throughout the first year of life [117], a fact that underscores that infants continue to acquire ARGs during the complementary feeding period. This means that while the decrease in abundance of ARGs is a beneficial shift in the resistome that occurs during the complementary feeding period, this period is not unambiguously beneficial as this period also represents a shift in the resistome from bacteria with intrinsic ARGs to more transferable ARGs [116]. Despite the changes to the resistome that occur during this period, little research exists that examines the connection between complementary feeding diet and ARG carriage. Given the connections between diet and ARGs in adults [49] and the correlation between increased carbohydrate utilization genes and decreased ARG carriage [116], this is an area where more research is urgently needed to understand if the selection of some optimized set of foods may also reduce infant acquisition of new ARGs during this time period.
There are additional mechanisms by which the solid food introduced to the infant diet can contribute to ARG proliferation. Agricultural animals used for food are often farmed using antibiotics extensively for the prevention of diseases and support of growth, which invariably adds to the concentration of ARGs present in these foods [118]. When humans consume foods from these sources, they risk the transfer of ARG carrying bacteria into their gut microbiome, thus adding to the pool of resistant genes and elevating ARG infection risks [119]. Although previous studies have examined and promoted the role of animal protein sources in infant nutrition (as complementary foods) to fill the nutrient deficiencies observed in breast milk when infants’ nutritional needs increase during weaning [120,121], research has associated consumption of red meat in adults to increased carriage of multidrug-resistant E. coli [122]. Therefore, weaning diet has the potential to have both positive and negative effects on infant carriage of ARGs, and more research is needed to understand the extent to which fiber and animal product consumption interact to shape the resistome.

7. Infant Gut Resistome as a Source of ARGs

Not all ARGs are of equal concern for public health; genes on mobile genetic elements are of greater concern than chromosomal resistance genes [42,104,123,124]. ARGs on mobile genetic elements can undergo HGT from one microorganism to another [23]. ARGs on mobile genetic elements in biomes with greater bacterial diversity and density are more likely to undergo HGT [125]. As the infant gut microbiome is enriched for ARGs and is more likely to come in contact with human-relevant pathogens than other biomes (e.g., the soil biome), the infant gut microbiome is a potential hotspot for ARG transmission. The infant gut microbiome can potentially serve as a source of nosocomial ARGs, for example, in inhalable dust [126]. There is also an increased chance for transmission of resistant pathogens in childcare facilities as young children are immunologically naïve and at greater risk of infection generally, and there are multiple outbreak reports of antimicrobial-resistant organisms occurring in daycares [127].

8. Conclusions

The intricate interaction between ARGs, the gut microbiome, and infant nutrition calls for more investigation to develop strategies that are efficacious and capable of rapidly arresting AMR spread. As expounded here, the neonatal period through the introduction of complementary foods represents a critical window of time during which the infant gut microbiome develops. This makes it a critical time period for the establishment of a healthy gut microbial community. Because the gut resistome is part of the gut microbiome, the establishment of the gut microbiome can have a significant influence on ARG carriage. Of particular importance is the possibility that diet can help to shape the resistome and thereby control the spread of ARGs. Early evidence indicates that dietary differences are associated with differences in the gut resistome and carriage of ARGs, but further research is needed to tease apart the complex relationship between diet and ARG carriage before specific recommendations for a diet to reduce ARG carriage can be made. This is especially true since, as previously discussed in this paper, dietary fiber is associated with decreased ARG levels and meat consumption with increased ARG infection risk, but there is not a clear difference in ARG carriage between omnivores and vegans.
To enable future recommendations, more original studies seeking to elucidate the underlying mechanisms and role of diet in infant acquisition and transmission of ARGs and to understand the health implications of a changing resistome over time are needed. Such studies should consider detailed analysis of different dietary components. For example, are fibers from specific foods associated with decreased ARG carriage? Consumption of which animal products are associated with the introduction of new ARGs? Future studies should also emphasize the need for multidisciplinary approaches to holistically establish the links between ARGs, the infant gut microbiome, and nutrition through the lens of the One Health approach.

Author Contributions

Conceptualization of this article was done by D.H.T. R.J.T. completed the literature review necessary to this project, and wrote the first draft. D.H.T. and R.J.T. collaborated to substantially revise additional drafts of this paper. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

This is a review article. No new data was generated for this manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Murray, C.J.; Ikuta, K.S.; Sharara, F.; Swetschinski, L.; Aguilar, G.R.; Gray, A.; Han, C.; Bisignano, C.; Rao, P.; Wool, E. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022, 399, 629–655. [Google Scholar] [CrossRef] [PubMed]
  2. Centers for Disease Control and Prevention; US Department of Health and Human Services. Antibiotic Resistance Threats in the United States 2013; Centers for Disease Control and Prevention: Atlanta, GA, USA, 2013.
  3. Centers for Disease Control and Prevention. CDC’s Antibiotic Resistance Threats in the United States, 2019; Centers for Disease Control and Prevention: Atlanta, GA, USA, 2019.
  4. Nelson, R.E.; Hatfield, K.M.; Wolford, H.; Samore, M.H.; Scott, R.D.; Reddy, S.C.; Olubajo, B.; Paul, P.; Jernigan, J.A.; Baggs, J. National estimates of healthcare costs associated with multidrug-resistant bacterial infections among hospitalized patients in the United States. Clin. Infect. Dis. 2021, 72, S17–S26. [Google Scholar] [CrossRef]
  5. Romandini, A.; Pani, A.; Schenardi, P.A.; Pattarino, G.A.C.; De Giacomo, C.; Scaglione, F. Antibiotic resistance in pediatric infections: Global emerging threats, predicting the near future. Antibiotics 2021, 10, 393. [Google Scholar] [CrossRef]
  6. Laxminarayan, R.; Matsoso, P.; Pant, S.; Brower, C.; Røttingen, J.-A.; Klugman, K.; Davies, S. Access to effective antimicrobials: A worldwide challenge. Lancet 2016, 387, 168–175. [Google Scholar] [CrossRef]
  7. Chatterjee, A.; Modarai, M.; Naylor, N.R.; Boyd, S.E.; Atun, R.; Barlow, J.; Holmes, A.H.; Johnson, A.; Robotham, J.V. Quantifying drivers of antibiotic resistance in humans: A systematic review. Lancet Infect. Dis. 2018, 18, e368–e378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Versporten, A.; Bielicki, J.; Drapier, N.; Sharland, M.; Goossens, H.; Group, A.P.; Calle, G.M.; Garrahan, J.P.; Clark, J.; Cooper, C. The Worldwide Antibiotic Resistance and Prescribing in European Children (ARPEC) point prevalence survey: Developing hospital-quality indicators of antibiotic prescribing for children. J. Antimicrob. Chemother. 2016, 71, 1106–1117. [Google Scholar] [CrossRef] [Green Version]
  9. Rabbitts, J.A.; Groenewald, C.B. Epidemiology of pediatric surgery in the United States. Pediatr. Anesthesia 2020, 30, 1083–1090. [Google Scholar] [CrossRef]
  10. Miller, G.F.; Coffield, E.; Leroy, Z.; Wallin, R. Prevalence and costs of five chronic conditions in children. J. Sch. Nurs. 2016, 32, 357–364. [Google Scholar] [CrossRef]
  11. Omling, E.; Jarnheimer, A.; Rose, J.; Björk, J.; Meara, J.; Hagander, L. Population-based incidence rate of inpatient and outpatient surgical procedures in a high-income country. J. Br. Surg. 2018, 105, 86–95. [Google Scholar] [CrossRef] [Green Version]
  12. Patangia, D.V.; Ryan, C.A.; Dempsey, E.; Stanton, C.; Ross, R.P. Vertical transfer of antibiotics and antibiotic resistant strains across the mother/baby axis. Trends Microbiol. 2022, 30, 47–56. [Google Scholar] [CrossRef]
  13. Nogacka, A.; Salazar, N.; Suárez, M.; Milani, C.; Arboleya, S.; Solís, G.; Fernández, N.; Alaez, L.; Hernández-Barranco, A.M.; de Los Reyes-Gavilán, C.G. Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates. Microbiome 2017, 5, 93. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Li, W.; Tapiainen, T.; Brinkac, L.; Lorenzi, H.A.; Moncera, K.; Tejesvi, M.V.; Salo, J.; Nelson, K.E. Vertical transmission of gut microbiome and antimicrobial resistance genes in infants exposed to antibiotics at birth. J. Infect. Dis. 2021, 224, 1236–1246. [Google Scholar] [CrossRef] [PubMed]
  15. Gibson, M.K.; Crofts, T.S.; Dantas, G. Antibiotics and the developing infant gut microbiota and resistome. Curr. Opin. Microbiol. 2015, 27, 51–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Greenwood, C.; Morrow, A.L.; Lagomarcino, A.J.; Altaye, M.; Taft, D.H.; Yu, Z.; Newburg, D.S.; Ward, D.V.; Schibler, K.R. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J. Pediatr. 2014, 165, 23–29. [Google Scholar] [CrossRef] [Green Version]
  17. Irfan, M.; Almotiri, A.; AlZeyadi, Z. Antimicrobial Resistance and Its Drivers—A Review. Antibiotics 2022, 11, 1362. [Google Scholar] [CrossRef]
  18. Tenover, F.C. Mechanisms of antimicrobial resistance in bacteria. Am. J. Med. 2006, 119, S3–S10. [Google Scholar] [CrossRef]
  19. Ventola, C.L. The antibiotic resistance crisis: Part 1: Causes and threats. Pharm. Ther. 2015, 40, 277. [Google Scholar]
  20. Zankari, E.; Allesøe, R.; Joensen, K.G.; Cavaco, L.M.; Lund, O.; Aarestrup, F.M. PointFinder: A novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens. J. Antimicrob. Chemother. 2017, 72, 2764–2768. [Google Scholar] [CrossRef] [Green Version]
  21. Pehrsson, E.C.; Forsberg, K.J.; Gibson, M.K.; Ahmadi, S.; Dantas, G. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs. Front. Microbiol. 2013, 4, 145. [Google Scholar] [CrossRef] [Green Version]
  22. Sun, D.; Jeannot, K.; Xiao, Y.; Knapp, C. Editorial: Horizontal gene transfer mediated bacterial antibiotic resistance. Front. Microbiol. 2019, 10, 1933. [Google Scholar] [CrossRef] [Green Version]
  23. Martínez, J.L.; Baquero, F. Emergence and spread of antibiotic resistance: Setting a parameter space. Upsala J. Med. Sci. 2014, 119, 68–77. [Google Scholar] [CrossRef]
  24. Hu, Y.; Yang, X.; Li, J.; Lv, N.; Liu, F.; Wu, J.; Lin, I.Y.; Wu, N.; Weimer, B.C.; Gao, G.F. The bacterial mobile resistome transfer network connecting the animal and human microbiomes. Appl. Environ. Microbiol. 2016, 82, 6672–6681. [Google Scholar] [CrossRef] [Green Version]
  25. Galhano, B.S.P.; Ferrari, R.G.; Panzenhagen, P.; de Jesus, A.C.; Conte-Junior, C.A. Antimicrobial Resistance Gene Detection Methods for Bacteria in Animal-Based Foods: A Brief Review of Highlights and Advantages. Microorganisms 2021, 9, 923. [Google Scholar] [CrossRef]
  26. Landan, G.; Cohen, G.; Aharonowitz, Y.; Shuali, Y.; Graur, D.; Shiffman, D. Evolution of isopenicillin N synthase genes may have involved horizontal gene transfer. Mol. Biol. Evol. 1990, 7, 399–406. [Google Scholar] [CrossRef] [Green Version]
  27. Benveniste, R.; Davies, J. Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc. Natl. Acad. Sci. USA 1973, 70, 2276–2280. [Google Scholar] [CrossRef]
  28. Frye, J.G.; Jesse, T.; Long, F.; Rondeau, G.; Porwollik, S.; McClelland, M.; Jackson, C.R.; Englen, M.; Fedorka-Cray, P.J. DNA microarray detection of antimicrobial resistance genes in diverse bacteria. Int. J. Antimicrob. Agents 2006, 27, 138–151. [Google Scholar] [CrossRef] [PubMed]
  29. Fluit, A.C.; Visser, M.R.; Schmitz, F.J. Molecular detection of antimicrobial resistance. Clin. Microbiol. Rev. 2001, 14, 836–871. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  30. McArthur, A.G.; Waglechner, N.; Nizam, F.; Yan, A.; Azad, M.A.; Baylay, A.J.; Bhullar, K.; Canova, M.J.; De Pascale, G.; Ejim, L.; et al. The comprehensive antibiotic resistance database. Antimicrob. Agents Chemother. 2013, 57, 3348–3357. [Google Scholar] [CrossRef] [Green Version]
  31. Oniciuc, E.A.; Likotrafiti, E.; Alvarez-Molina, A.; Prieto, M.; Santos, J.A.; Alvarez-Ordóñez, A. The Present and Future of Whole Genome Sequencing (WGS) and Whole Metagenome Sequencing (WMS) for Surveillance of Antimicrobial Resistant Microorganisms and Antimicrobial Resistance Genes across the Food Chain. Genes 2018, 9, 268. [Google Scholar] [CrossRef] [Green Version]
  32. Lee, K.; Kim, D.-W.; Cha, C.-J. Overview of bioinformatic methods for analysis of antibiotic resistome from genome and metagenome data. J. Microbiol. 2021, 59, 270–280. [Google Scholar] [CrossRef] [PubMed]
  33. Nowrotek, M.; Jałowiecki, Ł.; Harnisz, M.; Płaza, G.A. Culturomics and metagenomics: In understanding of environmental resistome. Front. Environ. Sci. Eng. 2019, 13, 40. [Google Scholar] [CrossRef] [Green Version]
  34. Velazquez-Meza, M.E.; Galarde-López, M.; Carrillo-Quiróz, B.; Alpuche-Aranda, C.M. Antimicrobial resistance: One Health approach. Veter-World 2022, 15, 743. [Google Scholar] [CrossRef]
  35. Aslam, B.; Khurshid, M.; Arshad, M.I.; Muzammil, S.; Rasool, M.; Yasmeen, N.; Shah, T.; Chaudhry, T.H.; Rasool, M.H.; Shahid, A. Antibiotic resistance: One health one world outlook. Front. Cell. Infect. Microbiol. 2021, 11, 771510. [Google Scholar] [CrossRef]
  36. World Health Organization. One Health Joint Plan of Action (2022–2026): Working Together for the Health of Humans, Animals, Plants and the Environment; World Health Organization: Geneva, Switzerland, 2022. [Google Scholar]
  37. Destoumieux-Garzón, D.; Mavingui, P.; Boetsch, G.; Boissier, J.; Darriet, F.; Duboz, P.; Fritsch, C.; Giraudoux, P.; Le Roux, F.; Morand, S. The one health concept: 10 years old and a long road ahead. Front. Veter-Sci. 2018, 5, 14. [Google Scholar] [CrossRef] [Green Version]
  38. Collignon, P.J.; McEwen, S.A. One health—Its importance in helping to better control antimicrobial resistance. Trop. Med. Infect. Dis. 2019, 4, 22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  39. Shrestha, K.; Acharya, K.P.; Shrestha, S. One health: The interface between veterinary and human health. Int. J. One Health 2018, 4, 8–14. [Google Scholar] [CrossRef] [Green Version]
  40. Stålsby Lundborg, C.; Diwan, V.; Pathak, A.; Purohit, M.R.; Shah, H.; Sharma, M.; Mahadik, V.K.; Tamhankar, A.J. Protocol: A ‘One health’two year follow-up, mixed methods study on antibiotic resistance, focusing children under 5 and their environment in rural India. BMC Public Health 2015, 15, 1321. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  41. World Health Organization. Neglected Tropical Diseases and One Health: Gearing up Against Antimicrobial Resistance to Secure the Safety of Future Generations: Meeting Report, 24 November 2020; World Health Organization: Geneva, Switzerland, 2021. [Google Scholar]
  42. Zhang, A.-N.; Gaston, J.M.; Dai, C.L.; Zhao, S.; Poyet, M.; Groussin, M.; Yin, X.; Li, L.-G.; van Loosdrecht, M.; Topp, E. An omics-based framework for assessing the health risk of antimicrobial resistance genes. Nat. Commun. 2021, 12, 4765. [Google Scholar] [CrossRef]
  43. Lederberg, J.; McCray, A.T. Ome SweetOmics--A genealogical treasury of words. Science 2001, 15, 8. [Google Scholar]
  44. Wright, G.D. The antibiotic resistome: The nexus of chemical and genetic diversity. Nat. Rev. Microbiol. 2007, 5, 175–186. [Google Scholar] [CrossRef]
  45. Anthony, W.E.; Burnham, C.-A.D.; Dantas, G.; Kwon, J.H. The gut microbiome as a reservoir for antimicrobial resistance. J. Infect. Dis. 2021, 223, S209–S213. [Google Scholar] [CrossRef] [PubMed]
  46. David, L.A.; Maurice, C.F.; Carmody, R.N.; Gootenberg, D.B.; Button, J.E.; Wolfe, B.E.; Ling, A.V.; Devlin, A.S.; Varma, Y.; Fischbach, M.A. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014, 505, 559–563. [Google Scholar] [CrossRef] [Green Version]
  47. Wu, G.D.; Compher, C.; Chen, E.Z.; Smith, S.A.; Shah, R.D.; Bittinger, K.; Chehoud, C.; Albenberg, L.G.; Nessel, L.; Gilroy, E. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut 2016, 65, 63–72. [Google Scholar] [CrossRef]
  48. Tanes, C.; Bittinger, K.; Gao, Y.; Friedman, E.S.; Nessel, L.; Paladhi, U.R.; Chau, L.; Panfen, E.; Fischbach, M.A.; Braun, J.; et al. Role of dietary fiber in the recovery of the human gut microbiome and its metabolome. Cell Host Microbe 2021, 29, 394–407.e395. [Google Scholar] [CrossRef] [PubMed]
  49. Oliver, A.; Xue, Z.; Villanueva, Y.T.; Durbin-Johnson, B.; Alkan, Z.; Taft, D.H.; Liu, J.; Korf, I.; Laugero, K.D.; Stephensen, C.B. Association of diet and antimicrobial resistance in healthy US adults. mBio 2022, 13, e00101-22. [Google Scholar] [CrossRef]
  50. Angulo, F.J.; Baker, N.L.; Olsen, S.J.; Anderson, A.; Barrett, T.J. Antimicrobial use in agriculture: Controlling the transfer of antimicrobial resistance to humans. Semin. Pediatr. Infect. Dis. 2004, 15, 78–85. [Google Scholar] [CrossRef]
  51. Thanner, S.; Drissner, D.; Walsh, F. Antimicrobial resistance in agriculture. mBio 2016, 7, e02227-15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. Van Boeckel, T.P.; Glennon, E.E.; Chen, D.; Gilbert, M.; Robinson, T.P.; Grenfell, B.T.; Levin, S.A.; Bonhoeffer, S.; Laxminarayan, R. Reducing antimicrobial use in food animals. Science 2017, 357, 1350–1352. [Google Scholar] [CrossRef] [Green Version]
  53. Manges, A.R.; Smith, S.P.; Lau, B.J.; Nuval, C.J.; Eisenberg, J.N.; Dietrich, P.S.; Riley, L.W. Retail Meat Consumption and the Acquisition of Antimicrobial Resistant Escherichia coli Causing Urinary Tract Infections: A Case–Control Study. Foodborne Pathog. Dis. 2007, 4, 419–431. [Google Scholar] [CrossRef] [Green Version]
  54. da Silva, S.F.; Reis, I.B.; Monteiro, M.G.; Dias, V.C.; Machado, A.B.F.; da Silva, V.L.; Diniz, C.G. Influence of Human Eating Habits on Antimicrobial Resistance Phenomenon: Aspects of Clinical Resistome of Gut Microbiota in Omnivores, Ovolactovegetarians, and Strict Vegetarians. Antibiotics 2021, 10, 276. [Google Scholar] [CrossRef]
  55. Gosalbes, M.; Vallès, Y.; Jiménez-Hernández, N.; Balle, C.; Riva, P.; Miravet-Verde, S.; de Vries, L.E.; Llop, S.; Agersø, Y.; Sørensen, S.J. High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples. J. Dev. Orig. Health Dis. 2016, 7, 35–44. [Google Scholar] [CrossRef] [PubMed]
  56. Taft, D.H.; Liu, J.; Maldonado-Gomez, M.X.; Akre, S.; Huda, M.N.; Ahmad, S.; Stephensen, C.B.; Mills, D.A. Bifidobacterial dominance of the gut in early life and acquisition of antimicrobial resistance. Msphere 2018, 3, e00441-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. World Health Organization. Report of the Expert Consultation of the Optimal Duration of Exclusive Breastfeeding; World Health Organization: Geneva, Switzerland, 2001. [Google Scholar]
  58. Meek, J.Y.; Noble, L.; Section of Breastfeeding. Policy Statement: Breastfeeding and the Use of Human Milk. Pediatrics 2022, 150, e2022057988. [Google Scholar] [CrossRef]
  59. Andreas, N.J.; Kampmann, B.; Le-Doare, K.M. Human breast milk: A review on its composition and bioactivity. Early Hum. Dev. 2015, 91, 629–635. [Google Scholar] [CrossRef] [PubMed]
  60. Hassiotou, F.; Geddes, D.T. Immune cell–mediated protection of the mammary gland and the infant during breastfeeding. Adv. Nutr. 2015, 6, 267–275. [Google Scholar] [CrossRef] [Green Version]
  61. Victora, C.G.; Bahl, R.; Barros, A.J.; França, G.V.; Horton, S.; Krasevec, J.; Murch, S.; Sankar, M.J.; Walker, N.; Rollins, N.C. Breastfeeding in the 21st century: Epidemiology, mechanisms, and lifelong effect. Lancet 2016, 387, 475–490. [Google Scholar] [CrossRef] [Green Version]
  62. Laursen, M.F.; Bahl, M.I.; Licht, T.R. Settlers of our inner surface–factors shaping the gut microbiota from birth to toddlerhood. FEMS Microbiol. Rev. 2021, 45, fuab001. [Google Scholar] [CrossRef] [PubMed]
  63. Laursen, M.F. Gut microbiota development: Influence of diet from infancy to toddlerhood. Ann. Nutr. Metab. 2021, 77, 21–34. [Google Scholar] [CrossRef]
  64. Logan, W. The intestinal flora of infants and young children. J. Pathol. 1913, 18, 527–551. [Google Scholar] [CrossRef] [Green Version]
  65. Tannock, G.W.; Lawley, B.; Munro, K.; Gowri Pathmanathan, S.; Zhou, S.J.; Makrides, M.; Gibson, R.A.; Sullivan, T.; Prosser, C.G.; Lowry, D.; et al. Comparison of the compositions of the stool microbiotas of infants fed goat milk formula, cow milk-based formula, or breast milk. Appl. Environ. Microbiol. 2013, 79, 3040–3048. [Google Scholar] [CrossRef] [Green Version]
  66. Ballard, O.; Morrow, A.L. Human milk composition: Nutrients and bioactive factors. Pediatr. Clin. 2013, 60, 49–74. [Google Scholar]
  67. Bode, L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 2012, 22, 1147–1162. [Google Scholar] [CrossRef] [Green Version]
  68. Smilowitz, J.T.; Lebrilla, C.B.; Mills, D.A.; German, J.B.; Freeman, S.L. Breast milk oligosaccharides: Structure-function relationships in the neonate. Annu. Rev. Nutr. 2014, 34, 143–169. [Google Scholar] [CrossRef] [Green Version]
  69. Lewis, Z.T.; Totten, S.M.; Smilowitz, J.T.; Popovic, M.; Parker, E.; Lemay, D.G.; Van Tassell, M.L.; Miller, M.J.; Jin, Y.-S.; German, J.B. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome 2015, 3, 13. [Google Scholar] [CrossRef] [Green Version]
  70. Marcobal, A.; Barboza, M.; Froehlich, J.W.; Block, D.E.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Consumption of human milk oligosaccharides by gut-related microbes. J. Agric. Food Chem. 2010, 58, 5334–5340. [Google Scholar] [CrossRef] [Green Version]
  71. Bode, L. The functional biology of human milk oligosaccharides. Early Hum. Dev. 2015, 91, 619–622. [Google Scholar] [CrossRef]
  72. Weichert, S.; Koromyslova, A.; Singh, B.K.; Hansman, S.; Jennewein, S.; Schroten, H.; Hansman, G.S. Structural basis for norovirus inhibition by human milk oligosaccharides. J. Virol. 2016, 90, 4843–4848. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Sela, D.A.; Mills, D.A. Nursing our microbiota: Molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol. 2010, 18, 298–307. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Taft, D.H.; Lewis, Z.T.; Nguyen, N.; Ho, S.; Masarweh, C.; Dunne-Castagna, V.; Tancredi, D.J.; Huda, M.N.; Stephensen, C.B.; Hinde, K. Bifidobacterium species colonization in infancy: A global cross-sectional comparison by population history of breastfeeding. Nutrients 2022, 14, 1423. [Google Scholar] [CrossRef]
  75. Crits-Christoph, A.; Hallowell, H.A.; Koutouvalis, K.; Suez, J. Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome. Gut Microbes 2022, 14, 2055944. [Google Scholar] [CrossRef] [PubMed]
  76. Kennedy, K.M.; de Goffau, M.C.; Perez-Muñoz, M.E.; Arrieta, M.-C.; Bäckhed, F.; Bork, P.; Braun, T.; Bushman, F.D.; Dore, J.; de Vos, W.M.; et al. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature 2023, 613, 639–649. [Google Scholar] [CrossRef] [PubMed]
  77. Dominguez-Bello, M.G.; Costello, E.K.; Contreras, M.; Magris, M.; Hidalgo, G.; Fierer, N.; Knight, R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA 2010, 107, 11971–11975. [Google Scholar] [CrossRef]
  78. Fouhy, F.; Guinane, C.M.; Hussey, S.; Wall, R.; Ryan, C.A.; Dempsey, E.M.; Murphy, B.; Ross, R.P.; Fitzgerald, G.F.; Stanton, C. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob. Agents Chemother. 2012, 56, 5811–5820. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  79. Moore, A.M.; Ahmadi, S.; Patel, S.; Gibson, M.K.; Wang, B.; Ndao, I.M.; Deych, E.; Shannon, W.; Tarr, P.I.; Warner, B.B. Gut resistome development in healthy twin pairs in the first year of life. Microbiome 2015, 3, 27. [Google Scholar] [CrossRef] [Green Version]
  80. Bratzler, D.W.; Dellinger, E.P.; Olsen, K.M.; Perl, T.M.; Auwaerter, P.G.; Bolon, M.K.; Fish, D.N.; Napolitano, L.M.; Sawyer, R.G.; Slain, D.; et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am. J. Health-Syst. Pharm. 2013, 70, 195–283. [Google Scholar] [CrossRef] [Green Version]
  81. Schrag, S.J.; Verani, J.R. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: Experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine 2013, 31, D20–D26. [Google Scholar] [CrossRef] [Green Version]
  82. Puopolo, K.M.; Lynfield, R.; Cummings, J.J.; Hand, I.; Adams-Chapman, I.; Poindexter, B.; Stewart, D.L.; Aucott, S.W.; Goldsmith, J.P.; Mowitz, M. Management of infants at risk for group B streptococcal disease. Pediatrics 2019, 144, e20191881. [Google Scholar] [CrossRef] [Green Version]
  83. Donovan, B.M.; Abreo, A.; Ding, T.; Gebretsadik, T.; Turi, K.N.; Yu, C.; Ding, J.; Dupont, W.D.; Stone, C.A.; Hartert, T.V.; et al. Dose, Timing, and Type of Infant Antibiotic Use and the Risk of Childhood Asthma. Clin. Infect. Dis. 2019, 70, 1658–1665. [Google Scholar] [CrossRef]
  84. Stam, J.; van Stuijvenberg, M.; Grüber, C.; Mosca, F.; Arslanoglu, S.; Chirico, G.; Braegger, C.P.; Riedler, J.; Boehm, G.; Sauer, P.J.; et al. Antibiotic use in infants in the first year of life in five European countries. Acta Paediatr. 2012, 101, 929–934. [Google Scholar] [CrossRef] [Green Version]
  85. Thänert, R.; Sawhney, S.S.; Schwartz, D.J.; Dantas, G. The resistance within: Antibiotic disruption of the gut microbiome and resistome dynamics in infancy. Cell Host Microbe 2022, 30, 675–683. [Google Scholar] [CrossRef]
  86. Cox, L.M.; Blaser, M.J. Antibiotics in early life and obesity. Nat. Rev. Endocrinol. 2015, 11, 182–190. [Google Scholar] [CrossRef]
  87. Gasparrini, A.J.; Crofts, T.S.; Gibson, M.K.; Tarr, P.I.; Warner, B.B.; Dantas, G. Antibiotic perturbation of the preterm infant gut microbiome and resistome. Gut Microbes 2016, 7, 443–449. [Google Scholar] [CrossRef] [PubMed]
  88. Loo, E.X.L.; Zain, A.; Yap, G.C.; Purbojati, R.W.; Drautz-Moses, D.I.; Koh, Y.Q.; Chong, Y.S.; Tan, K.H.; Gluckman, P.D.; Yap, F.; et al. Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema. BMC Infect. Dis. 2020, 20, 312. [Google Scholar] [CrossRef] [PubMed]
  89. Reichler, M.R.; Allphin, A.A.; Breiman, R.F.; Schreiber, J.R.; Arnold, J.E.; McDougal, L.K.; Facklam, R.R.; Boxerbaum, B.; May, D.; Walton, R.O.; et al. The Spread of Multiply Resistant Streptococcus pneumoniae at a Day Care Center in Ohio. J. Infect. Dis. 1992, 166, 1346–1353. [Google Scholar] [CrossRef] [PubMed]
  90. Guardabassi, L.; Loeber, M.E.; Jacobson, A. Transmission of multiple antimicrobial-resistant Staphylococcus intermedius between dogs affected by deep pyoderma and their owners. Vet. Microbiol. 2004, 98, 23–27. [Google Scholar] [CrossRef]
  91. Wolfs, T.F.; Duim, B.; Geelen, S.P.; Rigter, A.; Thomson-Carter, F.; Fleer, A.; Wagenaar, J.A. Neonatal sepsis by Campylobacter jejuni: Genetically proven transmission from a household puppy. Clin. Infect. Dis. 2001, 32, E97–E99. [Google Scholar] [CrossRef]
  92. Pärnänen, K.; Karkman, A.; Hultman, J.; Lyra, C.; Bengtsson-Palme, J.; Larsson, D.G.J.; Rautava, S.; Isolauri, E.; Salminen, S.; Kumar, H.; et al. Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nat. Commun. 2018, 9, 3891. [Google Scholar] [CrossRef] [Green Version]
  93. Wajda, Ł.; Ostrowski, A.; Błasiak, E.; Godowska, P. Enterococcus faecium Isolates Present in Human Breast Milk Might Be Carriers of Multi-Antibiotic Resistance Genes. Bacteria 2022, 1, 66–87. [Google Scholar] [CrossRef]
  94. Kozak, K.; Charbonneau, D.; Sanozky-Dawes, R.; Klaenhammer, T. Characterization of bacterial isolates from the microbiota of mothers’ breast milk and their infants. Gut Microbes 2015, 6, 341–351. [Google Scholar] [CrossRef] [Green Version]
  95. Pärnänen, K.M.M.; Hultman, J.; Markkanen, M.; Satokari, R.; Rautava, S.; Lamendella, R.; Wright, J.; McLimans, C.J.; Kelleher, S.L.; Virta, M.P. Early-life formula feeding is associated with infant gut microbiota alterations and an increased antibiotic resistance load. Am. J. Clin. Nutr. 2021, 115, 407–421. [Google Scholar] [CrossRef]
  96. Casaburi, G.; Duar, R.M.; Vance, D.P.; Mitchell, R.; Contreras, L.; Frese, S.A.; Smilowitz, J.T.; Underwood, M.A. Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria. Antimicrob. Resist. Infect. Control 2019, 8, 131. [Google Scholar] [CrossRef]
  97. Siimes, M.A.; Salmenperä, L.; Perheentupa, J. Exclusive breast-feeding for 9 months: Risk of iron deficiency. J. Pediatr. 1984, 104, 196–199. [Google Scholar] [CrossRef] [PubMed]
  98. Dewey, K.G. The challenge of meeting nutrient needs of infants and young children during the period of complementary feeding: An evolutionary perspective. J. Nutr. 2013, 143, 2050–2054. [Google Scholar] [PubMed] [Green Version]
  99. Arimond, M.; Ruel, M.T. Dietary diversity is associated with child nutritional status: Evidence from 11 demographic and health surveys. J. Nutr. 2004, 134, 2579–2585. [Google Scholar] [CrossRef] [Green Version]
  100. Woo, J.G.; Herbers, P.M.; McMahon, R.J.; Davidson, B.S.; Ruiz-Palacios, G.M.; Peng, Y.-M.; Morrow, A.L. Longitudinal development of infant complementary diet diversity in 3 international cohorts. J. Pediatr. 2015, 167, 969–974.e961. [Google Scholar] [CrossRef]
  101. Cummins, A.; Thompson, F. Effect of breast milk and weaning on epithelial growth of the small intestine in humans. Gut 2002, 51, 748–754. [Google Scholar] [CrossRef] [Green Version]
  102. Wen, J.; Xu, Q.; Zhao, W.; Hu, C.; Zou, X.; Dong, X. Effects of early weaning on intestinal morphology, digestive enzyme activity, antioxidant status, and cytokine status in domestic pigeon squabs (Columba livia). Poult. Sci. 2022, 101, 101613. [Google Scholar] [CrossRef]
  103. Stewart, C.J.; Ajami, N.J.; O’Brien, J.L.; Hutchinson, D.S.; Smith, D.P.; Wong, M.C.; Ross, M.C.; Lloyd, R.E.; Doddapaneni, H.; Metcalf, G.A. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 2018, 562, 583–588. [Google Scholar] [CrossRef] [Green Version]
  104. Bäckhed, F.; Roswall, J.; Peng, Y.; Feng, Q.; Jia, H.; Kovatcheva-Datchary, P.; Li, Y.; Xia, Y.; Xie, H.; Zhong, H. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015, 17, 690–703. [Google Scholar] [CrossRef] [Green Version]
  105. Laursen, M.F.; Andersen, L.B.; Michaelsen, K.F.; Mølgaard, C.; Trolle, E.; Bahl, M.I.; Licht, T.R. Infant gut microbiota development is driven by transition to family foods independent of maternal obesity. Msphere 2016, 1, e00069-15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  106. Yang, I.; Corwin, E.J.; Brennan, P.A.; Jordan, S.; Murphy, J.R.; Dunlop, A. The infant microbiome: Implications for infant health and neurocognitive development. Nurs. Res. 2016, 65, 76. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  107. Homann, C.-M.; Rossel, C.A.; Dizzell, S.; Bervoets, L.; Simioni, J.; Li, J.; Gunn, E.; Surette, M.G.; de Souza, R.J.; Mommers, M. Infants’ first solid foods: Impact on gut microbiota development in two intercontinental cohorts. Nutrients 2021, 13, 2639. [Google Scholar] [CrossRef]
  108. Marrs, T.; Jo, J.-H.; Perkin, M.R.; Rivett, D.W.; Witney, A.A.; Bruce, K.D.; Logan, K.; Craven, J.; Radulovic, S.; Versteeg, S.A. Gut microbiota development during infancy: Impact of introducing allergenic foods. J. Allergy Clin. Immunol. 2021, 147, 613–621.e619. [Google Scholar] [CrossRef]
  109. Smilowitz, J.; Amicucci, M.; Nandita, E.; Galermo, A.; Tu, D.; Taft, D.; Meier, A.; Kurudimov, K.; Oakes, L.; Mills, D.; et al. The Introduction of Plant-Derived Glycans in Exclusively 6-Month Old Breastfed Infants Alters Fecal Glycan Profiles and Microbial Metabolism (IMiND Study). Curr. Dev. Nutr. 2020, 4, 1082. [Google Scholar] [CrossRef]
  110. Tomova, A.; Bukovsky, I.; Rembert, E.; Yonas, W.; Alwarith, J.; Barnard, N.D.; Kahleova, H. The effects of vegetarian and vegan diets on gut microbiota. Front. Nutr. 2019, 6, 47. [Google Scholar] [CrossRef] [Green Version]
  111. Roberfroid, M.; Gibson, G.R.; Hoyles, L.; McCartney, A.L.; Rastall, R.; Rowland, I.; Wolvers, D.; Watzl, B.; Szajewska, H.; Stahl, B. Prebiotic effects: Metabolic and health benefits. Br. J. Nutr. 2010, 104, S1–S63. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  112. Parkar, S.G.; Frost, J.K.T.; Rosendale, D.; Stoklosinski, H.M.; Jobsis, C.M.H.; Hedderley, D.I.; Gopal, P. The sugar composition of the fibre in selected plant foods modulates weaning infants’ gut microbiome composition and fermentation metabolites in vitro. Sci. Rep. 2021, 11, 9292. [Google Scholar] [CrossRef]
  113. Bergström, A.; Skov, T.H.; Bahl, M.I.; Roager, H.M.; Christensen, L.B.; Ejlerskov, K.T.; Mølgaard, C.; Michaelsen, K.F.; Licht, T.R. Establishment of intestinal microbiota during early life: A longitudinal, explorative study of a large cohort of Danish infants. Appl. Environ. Microbiol. 2014, 80, 2889–2900. [Google Scholar] [CrossRef] [Green Version]
  114. Ogbo, F.A.; Nguyen, H.; Naz, S.; Agho, K.E.; Page, A. The association between infant and young child feeding practices and diarrhoea in Tanzanian children. Trop. Med. Health 2018, 46, 2. [Google Scholar] [CrossRef] [Green Version]
  115. Michaelsen, K.F.; Friis, H. Complementary feeding: A global perspective. Nutrition 1998, 14, 763–766. [Google Scholar] [CrossRef]
  116. Xu, X.; Feng, Q.; Zhang, T.; Cheng, Q.; Gao, Y.; Zhang, W.; Wu, Q.; Xu, K.; Li, Y.; Nguyen, N. Infant age negatively correlates with the overall load of gut resistome reflecting modifications of carbohydrate metabolism during early life. Res. Sq. 2023, 1–33. [Google Scholar] [CrossRef]
  117. Hetzer, B.; Orth-Höller, D.; Würzner, R.; Kreidl, P.; Lackner, M.; Müller, T.; Knabl, L.; Geisler-Moroder, D.R.; Mellmann, A.; Sesli, Ö.; et al. Enhanced acquisition of antibiotic-resistant intestinal E. coli during the first year of life assessed in a prospective cohort study. Antimicrob. Resist. Infect. Control 2019, 8, 79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  118. Marshall, B.M.; Levy, S.B. Food animals and antimicrobials: Impacts on human health. Clin. Microbiol. Rev. 2011, 24, 718–733. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  119. Zhu, Y.-G.; Johnson, T.A.; Su, J.-Q.; Qiao, M.; Guo, G.-X.; Stedtfeld, R.D.; Hashsham, S.A.; Tiedje, J.M. Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proc. Natl. Acad. Sci. USA 2013, 110, 3435–3440. [Google Scholar] [CrossRef] [PubMed]
  120. Theophilus, R.J.; Miller, M.; Oldewage-Theron, W.H.; Dawson, J. The winning weaning food (WWF): The development of a complementary food for food-insecure infants and young children in Malawi. Nutrients 2019, 11, 2292. [Google Scholar] [PubMed] [Green Version]
  121. Tang, M. The impact of complementary feeding foods of animal origin on growth and the risk of overweight in infants. Anim. Front. 2019, 9, 5–11. [Google Scholar] [CrossRef]
  122. Hu, Y.; Rubin, J.; Mussio, K.; Riley, L.W. Risk factors for faecal carriage of multidrug-resistant Escherichia coli in a college community: A penalised regression model. J. Glob. Antimicrob. Resist. 2021, 26, 166–173. [Google Scholar] [CrossRef]
  123. Becattini, S.; Taur, Y.; Pamer, E.G. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol. Med. 2016, 22, 458–478. [Google Scholar] [CrossRef] [Green Version]
  124. Azad, M.B.; Konya, T.; Maughan, H.; Guttman, D.S.; Field, C.J.; Chari, R.S.; Sears, M.R.; Becker, A.B.; Scott, J.A.; Kozyrskyj, A.L. Gut microbiota of healthy Canadian infants: Profiles by mode of delivery and infant diet at 4 months. Can. Med. Assoc. J. 2013, 185, 385–394. [Google Scholar] [CrossRef] [Green Version]
  125. Smillie, C.S.; Smith, M.B.; Friedman, J.; Cordero, O.X.; David, L.A.; Alm, E.J. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 2011, 480, 241–244. [Google Scholar] [CrossRef]
  126. Wu, D.; Jin, L.; Xie, J.; Liu, H.; Zhao, J.; Ye, D.; Li, X.-d. Inhalable antibiotic resistomes emitted from hospitals: Metagenomic insights into bacterial hosts, clinical relevance, and environmental risks. Microbiome 2022, 10, 19. [Google Scholar] [CrossRef] [PubMed]
  127. Holmes, S.J.; Morrow, A.L.; Pickering, L.K. Child-care practices: Effects of social change on the epidemiology of infectious diseases and antibiotic resistance. Epidemiol. Rev. 1996, 18, 10–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Theophilus, R.J.; Taft, D.H. Antimicrobial Resistance Genes (ARGs), the Gut Microbiome, and Infant Nutrition. Nutrients 2023, 15, 3177. https://doi.org/10.3390/nu15143177

AMA Style

Theophilus RJ, Taft DH. Antimicrobial Resistance Genes (ARGs), the Gut Microbiome, and Infant Nutrition. Nutrients. 2023; 15(14):3177. https://doi.org/10.3390/nu15143177

Chicago/Turabian Style

Theophilus, Rufus J., and Diana Hazard Taft. 2023. "Antimicrobial Resistance Genes (ARGs), the Gut Microbiome, and Infant Nutrition" Nutrients 15, no. 14: 3177. https://doi.org/10.3390/nu15143177

APA Style

Theophilus, R. J., & Taft, D. H. (2023). Antimicrobial Resistance Genes (ARGs), the Gut Microbiome, and Infant Nutrition. Nutrients, 15(14), 3177. https://doi.org/10.3390/nu15143177

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop