Open access peer-reviewed chapter

Metagenomics of Antimicrobial Resistance in Gut Microbiome

Written By

Madangchanok Imchen and Ranjith Kumavath

Submitted: 08 July 2017 Reviewed: 05 March 2018 Published: 09 May 2018

DOI: 10.5772/intechopen.76214

From the Edited Volume

Metagenomics for Gut Microbes

Edited by Ranjith N. Kumavath

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A healthy human body functions in sync with a wide array of gut microbes collectively known as human gut microbiome. They complement in a number of functions which are essential in our daily life such as in food metabolism. Various illnesses including colon cancer, autism, obesity, and autoimmune diseases have been linked to an imbalanced gut microbiota. Antibiotics are indispensable drug; however, the administration of antibiotics in humans as well as in animal farms has shown to increase antimicrobial resistance genes (ARGs) in gut microbiome. This is of serious concern since the commensals in gut microbiome could capture ARGs through horizontal gene transfer which in turn could cause postsurgical infections. In addition, numerous studies have consistently shown that the gut microbiome is unique to each individual. Hence, in-depth knowledge on the gut microbiota community and the factor responsible for shaping and spreading of ARGs is essential. This would in turn enable the development of custom-tailored personalized food and drugs in the future.


  • metagenomics
  • gut microbiome
  • antimicrobial resistance genes (ARGs) and gut resistome

1. Introduction

1.1. The gut microbiome and its significance

The human gut microbiome, also known as “second genome” [1], hosts over 100 trillion microorganisms [2] collectively covering over 150 folds more unique genes than the host [3, 4]. Several projects such as the Human Microbiome Project, MyNewGut, and Meta-HIT have been initiated with the aim to understand the entirety and the functional potential of gut microbiome and to find possible strategies to benefit the host though the alteration of gut microbiome [5]. The gut microbiome has been linked to various functions, some of which are discussed subsequently.

1.1.1. Gut microbiome is a necessary digestive “organ”

The gut microbiome is also considered as a “metabolically active organ” [6]. The distal human intestine is an anaerobic bioreactor consisting of numerous microbes having the ability to degrade and harvest nutrients which are otherwise inaccessible to the host [7]. In return, the host provides the raw materials and shelter to the microbiome. In this way, the host is relieved of various genotypic attributes which the microbiome complements. Studies have shown that the microbiome coevolved with us by having a mutualistic association [8]. It would seem that the microbiome might compete with the host for food and nutrients. However, conventional animals require 30% more calorie intake than the germfree counterparts in order to maintain the same body weight, implying that the microbiome actually aid in the host metabolism [9, 10].

1.1.2. Personalized gut microbiome

The gut microbiome, similar to fingerprint, has its own unique signature for every individual which is, however, very dynamic [11, 12]. The changes in the microbiota, also called dysbiosis, have also been associated to several health issues [13]. This has led to the possibility of personalized medicine and diet tailored uniquely for every individual depending on his/her unique microbiome [14].

1.1.3. The gut-microbiome-brain connection

Alterations in gut microbiota have also been linked to autism spectrum disorder (ASD) and gut-microbiome-brain connection. Maternal immune activation (MIA) mouse exhibits similar symptoms to ASD such as neurodevelopmental disorders, dysbiosis, alterations in gastrointestinal (GI), and serum metabolites [15, 16, 17, 18]. Such MIA mouse when treated with Bacteroides fragilis improves intestinal permeability, tight junction proteins, and colon cytokines IL-6 which is required by the MIA offspring for the development of behavioral deficits [9, 19]. Precursor 4-ethylphenol (4EP) found in MIA mice have also been shown to increase anxiety-like behavior in naïve mice. 4EP is produced by several species of Clostridium which are also abundant in MIA mice. Treatment with B. fragilis resorts the 4EP level in MIA further supporting the role of microbiota in behavioral development [9].

1.2. Types of ARGs in gut microbiome resistome

The gut microbiome resistome can be broadly classified into intrinsic and mobile resistance genes [20]. As the name suggests, intrinsic resistance genes are non-mobile resistance genes which are inherited and render tolerance to a particular drug without prior exposure. Although less mobile, there are possibilities of intrinsic resistance genes getting captured into mobile genetic elements (MGEs). Such events would turn it into mobile-resistant genes. Hence, studying such intrinsic resistance would provide knowledge on the mechanism and the possible treatment to tackle in case of outbreaks [20]. On the other hand, mobile resistomes are the resistance genes which are encoded in the highly mobile mobile genetic elements (MGE). Mobile genetic elements include plasmids, transposons, integrons, integrative conjugative elements, genomic islands, and phages [20, 21, 22, 23, 24, 25]. Resistance genes can get accumulated into a particular segment of DNA forming a special genomic island encoding multiple antimicrobial resistance genes (ARGs) called resistance islands (RIs). For instance, Acinetobacter baumannii Resistance Island of 86 kb is the largest known RI harboring 45 ARGs [26]. Resistance genes encode for proteins that render the microbe resistance to various antibiotics (Figure 1).

Figure 1.

Antibiotic resistance mechanisms: They are broadly classified into four types: (A) the influx of the antibiotics is disabled into the cell, (B) the antibiotics that manage to get into the cell is pumped out by active efflux pumps, (C) the target site for antibiotic in the cell is modified so that the antibiotic cannot bind, and (D) the antibiotics that enters the cells are degraded by the cell machinery.

1.3. Factors that shape and spread gut microbiome ARGs

It is essential to understand the factors that shape and spread ARGs in the gut microbiome since gut microbiota regulates the human body in a diverse way, many of which are yet to be known. It is indeed an important part of our body as discussed earlier which need special attention. However, the human gut microbiome is exposed to every food and drugs we consume. The microbiota is, therefore, reflected by the dynamic nature it faces. Cataloging ARGs in gut microbiome is essential in order to study and determine the source and the possible measure to tackle the problem.

1.3.1. Horizontal gene transfer through mobile genetic elements

Mobile genetic elements (MGEs) are transferred between microbes through horizontal gene transfer (HGT) involving conjugation, transduction, and transformation. Transformation is the capturing of naked DNA from the environment into the microbe. If the naked DNA has ARG encoded in it, the microbe taking up the naked DNA would gain resistance owning to the resistant gene encoded in the naked DNA. However, such events are found to be considerably rare in the mammalian gut [27]. Hence, comparatively, conjugation and transduction seem to have a higher impact in ARG horizontal gene transfer [28]. Conjugation involves the formation of mating bridge though which the ARGs are transferred from the donor to the recipient cell. Bacterial HGTs are more common among the same phylogenetic taxa [29]. ARG transfer was boosted between the commensal Escherichia coli and other pathogens during gut inflammation [30]. However, ARG transfer through conjugation was significantly reduced between E. coli strains in the healthy human gut since the intestinal epithelial cells produce a proteinaceous compound [28, 31] which could interfere with the conjugative process. In transduction, the ARG is encoded in the bacteriophages which get incorporated into the host once the bacteriophages invade a bacterium. It is postulated that transduction could be a major player in gut resistome [32] since the amount of phages and bacteria is equivalent in the intestinal tract [33, 34]. This is supported by the work of Goren et al. [35] showing that the phages isolated from antibiotic-treated mice when inoculated to aerobic microbiota culture showed higher ARG isolates when compared to culture which was treated with non-antibiotic-treated mice.

1.3.2. Gut resistome and antibiotic usage in farm animals

In the United States, nearly 80% of the antibiotics produced is used up in animal farm for treatment purposes [36]. As a result, the gut microbiome of farm animals is highly enriched in ARGs due to regular antibiotics treatment [37, 38]. ARGs enrichment up to 28,000 folds, including numerous unique ARGs, were detected in Chinese Swine farm [38] having efflux pumps, antibiotic deactivation, and cellular protection resistance mechanism. However, antibiotic-free organic pig guts were also found to harbor novel genes encoding resistance to the tetracyclines which were associated with putative mobile genetic elements [39]. Tetracycline resistance gene had the highest ratio of total ARGs according to a large-scale human gut microbiome analysis within the population from Denmark, Spain, and China. The study suggests the possibility of tetracycline resistance gene being transferred from animals since tetracyclines were highly used in animal farms [40, 41]. Subjects from country with comparatively tighter policies on antibiotic usages in humans and animals have considerably lesser ARG levels [42]. In addition, the antibiotic resistance genes revealed signature clustering of Chinese samples separate from other European countries thought single nucleotide polymorphisms (SNPs) analysis [41]. An independent study [43] on another population further supports this idea of ARG signature. The country-wise signature patterns could be linked to different policies adapted in different countries [28].

1.3.3. Travelers and migratory birds spread ARGs

ARGs can also spread through traveling. In a study involving Swedish students exchange programs to India or Central Africa, the level of sulfonamide, trimethoprim, and beta-lactams were increased after the completion of the exchange programs [44]. The spread of ARGs can also be affected widely by migratory birds, which fly long distances [45].

1.3.4. Antibiotic therapy enriches ARGs

Gut microbiome is a reservoir of ARGs which can indirectly pass the ARGs into the environment. The application of antibiotics has been largely linked to increase in ARGs. Resistance to aminoglycosides was found to increase after admitting to intensive care unit (ICU) [46]. ARGs were also found to increase on patients after treatment with antibiotics [47]. Studies on large-scale human gut samples from 10 different countries have shown that the ARGs in gut microbiome are highly influenced by the antibiotic usage and food products [48] while other factors such as age, sex, body mass index (BMI), and health status did not show significant contribution to ARGs level. The administration of cephalosporin, cefprozil, increased Lachnoclostridium bolteae in 16 out of 18 participants, as revealed from a study by Raymond et al. [49]. It also increased opportunistic pathogen Enterobacter cloacae in those participants whose initial microbiome diversity was comparatively lower. The treatment also enriched ARGs which were undetectable before the treatment. The alternation in the microbiome was specific to each subject, however, in a specific and reproducible manner. The authors, Raymond et al. [49], hypothesized that the initial analysis of microbiome before the treatment of antibiotics could bypass adverse effects during and after the antibiotic treatments. Nonetheless, the reduction of ARGs was seen in some studies when combinatorial antibiotic treatment was administrated [28, 46, 47]. This could happen when the resistant microbe is susceptible to another antibiotic when given in combination [28]. The application of antibiotic treatment, in addition to alteration of gut microbiome, can also cause long-term persistence of the ARGs in the gut microbiota [50]. Hence, alternative approach to antibiotic therapy is of urgent need to avoid undesirable effects to the microbiota. Alternative therapies such as probiotic intervention, vaccination, and bacteriotherapy [51, 52, 53, 54] have been developed. However, such alternative strategies are still at infancy stage; hence, focus on such strategies have to be encouraged.

1.4. Gut microbiome ARGs

Human gut microbiota is a home to numerous commensals, microbes that derive benefit from the host without causing harm. However, such commensals can acquire ARGs from microbes that are merely passing through the gut which can cause serious postsurgical infections [20]. In addition, disruption in the composition of gut microbiome in animal models has shown to cause non-communicable diseases (NCDs) such as colon cancer, autism, obesity, and autoimmune diseases [55, 56]. Salyers et al. [57] proposed the concept of ARGs in human gut microbiome. Since then, the technological advancement in high-throughput robotic screening and next-generation-sequencing (NGS) technologies in the last decade has pushed the gut microbiota research into full swing [20].

1.4.1. The infants’ gut resistome

The infant microbiota is highly dynamic and susceptible to antibiotics [58]. The disruption of microbiota at such stage could have significant ill effects throughout life by interfering with the metabolic and immune system [59]. The infant microbiota development is linked to various factors such as the host genetic makeup, nutrition, and environment [60, 61, 62]. The microbiota of a new born baby, even without antibiotic treatment, harbors a diverse resistance gene in their resistome [63, 64]. However, antibiotic treatments increase the abundance of pathogenic Enterobacteriaceae and lower healthy microbiota such as Bifidobacteriaceae, Bacilli, and Lactobacillales spp. [59, 65, 66, 67]. It is believed that the Lactobacillus and Bifidobacterium spp. are originated from maternal microbiome which is an essential component for the development of infant gut microbiome [62, 68]. The treatment of L. acidophilus and Bifidobacterium as probiotics in low birthweight infants increases the daily weight gain and recedes morbidity [69, 70], possibly by promoting the healthy gut microbiome and intestinal epithelial layer [58, 71]. The two modes of delivery, vaginally and C-section, can also distinctly affect an infant’s microbiota in the first year after delivery. Vaginally delivered infants harbor comparatively higher resemblance to mother’s microbiota [72]. Microbes such as Bacteroides and Bifidobacterium are less frequent in C-section-delivered infants; however, an increased frequency of bacteria is associated to oral and skin [73]. Studies have also found that the microbiota of a 2-month infant and their mother shares distinction in resistome which includes broad-spectrum beta-lactam antibiotics to be found only in the infants [74]. In fact, comparison between infant and their mother to an unrelated infant showed no significant difference [74]. It is proposed that the host genetic makeup and the environmental factors could play a role in the shaping resistome [74]. Infant microbiota shapes into an adult-like by increasing the alpha diversity while reducing the beta diversity which continues until the age of 3 [60]. Maturation of the infant microbiota is also driven by the feeding habit. The addition of solid food does not induce the maturation of microbiota significantly. However, cessation of breastfeeding enriches the gut microbiota to adult-like [72]. Infants with breastfeeding are enriched by Bifidobacterium and Lactobacillus even at the age of 1 while infants who no longer breastfeed are enriched with Roseburia, Clostridium, and Anaerostipes, which are prevalent in adults. Functionally, polysaccharide-degrading genes are enriched only after the cessation of breastfeeding [72]. The microbiota also acquires significant essential amino acids, irons, and vitamins genes after 4 months, which are essential for normal brain development [9, 75]. Functional metagenomics from healthy infants and children isolated three novel ARGs and also demonstrated that the ARG in gut resistome is significantly higher than previously estimated [64, 76].

1.4.2. The adult gut resistome

Large-scale metagenomic study of 252 fecal metagenomes samples identified 50 antibiotic classes [42]. Tetracycline resistance gene, tetQ, is the most abundant resistance gene in fecal samples of Chinese, Danish, and Spanish individuals. In fact, tetracycline resistance genes were the most abundant genes in multiple studies [41, 42]. Although sufficient evidence for the diversity and abundance of ARGs have already been shown to light, the numbers could still be underestimated since during the annotation of metagenomic data, only those ARGs which have been identified and added into the database would yield a positive hit. This would exclude all the ARGs which have not yet been identified. For instance, 290 ARGs having an average similarity of only 69.5% against the GenBank were isolated using functional metagenomics of fecal samples from two healthy individuals [77].


2. Conclusion

Gut microbiome is an essential “organ” without which the host would be deprived of various benefits derived from the numerous gut microbes. The benefits range from food metabolism to the mental health of the host. Hence, it requires attention as much as any other organ in our body. Various studies have, however, noticed the dynamic nature in the compositing and diversity of the gut microbiome making it one of the most dynamic “organs” in us. In addition, the wide application of antibiotic treatment for human as well as animals has enriched the gut ARGs. Hence, strict polices has to be implemented in order to maintain a moderate antibiotics usage. In addition, the surge in ARGs is a clear indication that the research on antibiotic alternative is a necessity for the coming future.


  1. 1. Zmora N, Zeevi D, Korem T, Segal E, Elinav E. Taking it personally: Personalized utilization of the human microbiome in health and disease. Cell Host & Microbe. 2016;19(1):12-20
  2. 2. Tsai F, Coyle WJ. The microbiome and obesity: Is obesity linked to our gut flora? Current Gastroenterology Reports. 2009;11(4):307-313
  3. 3. Ghaisas S, Maher J, Kanthasamy A. Gut microbiome in health and disease: Linking the microbiome–gut–brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacology & Therapeutics. 2016;158:52-62
  4. 4. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR. A human gut microbial gene catalog established by metagenomic sequencing. Nature. 2010;464(7285):59
  5. 5. Roeselers G, Bouwman J, Levin E. The human gut microbiome, diet, and health:“post hoc non ergo propter hoc”. Trends in Food Science & Technology. 2016;57:302-305
  6. 6. Hooper LV, Midtvedt T, Gordon JI. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annual Review of Nutrition. 2002;22(1):283-307
  7. 7. Savage DC. Gastrointestinal microflora in mammalian nutrition. Annual Review of Nutrition. 1986;6(1):155-178
  8. 8. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915-1920
  9. 9. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451-1463
  10. 10. Wostmann BS, Larkin C, Moriarty A, Bruckner-Kardoss E. Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats. Laboratory Animal Science. 1983;33(1):46-50
  11. 11. Caporaso JG, Lauber CL, Costello EK, Berg-Lyons D, Gonzalez A, Stombaugh J, Knights D, Gajer P, Ravel J, Fierer N, Gordon JI. Moving pictures of the human microbiome. Genome Biology. 2011;12(5):R50
  12. 12. Franzosa EA, Huang K, Meadow JF, Gevers D, Lemon KP, Bohannan BJ, Huttenhower C. Identifying personal microbiomes using metagenomic codes. Proceedings of the National Academy of Sciences. 2015;112(22):E2930-E2938
  13. 13. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: An integrative view. Cell. 2012;148(6):1258-1270
  14. 14. Schloissnig S, Arumugam M, Sunagawa S, Mitreva M, Tap J, Zhu A, Waller A, Mende DR, Kultima JR, Martin J, Kota K. Genomic variation landscape of the human gut microbiome. Nature. 2013;493(7430):45
  15. 15. Boukthir S, Matoussi N, Belhadj A, Mammou S, Dlala SB, Helayem M, Rocchiccioli F, Bouzaidi S, Abdennebi M. Abnormal intestinal permeability in children with autism. La Tunisie medicale. 2010;88(9):685-686
  16. 16. Malkova NV, Collin ZY, Hsiao EY, Moore MJ, Patterson PH. Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain, Behavior, and Immunity. 2012;26(4):607-616
  17. 17. Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH. Activation of the maternal immune system alters cerebellar development in the offspring. Brain, Behavior, and Immunity. 2009;23(1):116-123
  18. 18. Williams BL, Hornig M, Parekh T, Lipkin WI. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio. 2012;3(1):e00261-11
  19. 19. Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. Journal of Neuroscience. 2007;27(40):10695-10702
  20. 20. Hu Y, Gao GF, Zhu B. The antibiotic resistome: Gene flow in environments, animals and human beings. Frontiers of Medicine. 2017:1-8
  21. 21. Bennett PM. Plasmid encoded antibiotic resistance: Acquisition and transfer of antibiotic resistance genes in bacteria. British Journal of Pharmacology. 2008;153(S1):S347-S357
  22. 22. Dobrindt U, Hochhut B, Hentschel U, Hacker J. Genomic islands in pathogenic and environmental microorganisms. Nature Reviews. Microbiology. 2004;2(5):414
  23. 23. Hu Y, Zhu Y, Ma Y, Liu F, Lu N, Yang X, Luan C, Yi Y, Zhu B. Genomic insights into intrinsic and acquired drug resistance mechanisms in Achromobacter xylosoxidans. Antimicrobial Agents and Chemotherapy. 2015;59(2):1152-1161
  24. 24. Rice LB. Tn916 family conjugative transposons and dissemination of antimicrobial resistance determinants. Antimicrobial Agents and Chemotherapy. 1998;42(8):1871-1877
  25. 25. Rowe-Magnus DA, Mazel D. The role of integrons in antibiotic resistance gene capture. International Journal of Medical Microbiology. 2002;292(2):115-125
  26. 26. Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L, Richet H, Robert C, Mangenot S, Abergel C, Nordmann P. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genetics. 2006;2(1):e7
  27. 27. Nordgård L, Brusetti L, Raddadi N, Traavik T, Averhoff B, Nielsen KM. An investigation of horizontal transfer of feed introduced DNA to the aerobic microbiota of the gastrointestinal tract of rats. BMC Research Notes. 2012;5(1):170
  28. 28. Van Schaik W. The human gut resistome. Philosophical Transactions of Royal Society B. 2015;370(1670):20140087
  29. 29. Hu Y, Yang X, Li J, Lv N, Liu F, Wu J, Lin IY, Wu N, Weimer BC, Gao GF, Liu Y. The bacterial mobile resistome transfer network connecting the animal and human microbiomes. Applied and Environmental Microbiology. 2016;82(22):6672-6681
  30. 30. Stecher B, Denzler R, Maier L, Bernet F, Sanders MJ, Pickard DJ, Barthel M, Westendorf AM, Krogfelt KA, Walker AW, Ackermann M. Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. Proceedings of the National Academy of Sciences. 2012;109(4):1269-1274
  31. 31. Machado AMD, Sommer MO. Human intestinal cells modulate conjugational transfer of multidrug resistance plasmids between clinical Escherichia coli isolates. PLoS One. 2014;9(6):e100739
  32. 32. Mills S, Shanahan F, Stanton C, Hill C, Coffey A, Ross RP. Movers and shakers: Influence of bacteriophages in shaping the mammalian gut microbiota. Gut Microbes. 2013;4(1):4-16
  33. 33. Kim MS, Park EJ, Roh SW, Bae JW. Diversity and abundance of single-stranded DNA viruses in human feces. Applied and Environmental Microbiology. 2011;77(22):8062-8070
  34. 34. Reyes A, Semenkovich NP, Whiteson K, Rohwer F, Gordon JI. Going viral: Next generation sequencing applied to human gut phage populations. Nature Reviews. Microbiology. 2012;10(9):607
  35. 35. Goren MG, Carmeli Y, Schwaber MJ, Chmelnitsky I, Schechner V, Navon-Venezia S. Transfer of carbapenem-resistant plasmid from Klebsiella pneumoniae ST258 to Escherichia coli in patient. Emerging Infectious Diseases. 2010;16(6):1014
  36. 36. Yap MNF. The double life of antibiotics. Missouri Medicine. 2013;110(4):320
  37. 37. Cheng W, Chen H, Su C, Yan S. Abundance and persistence of antibiotic resistance genes in livestock farms: A comprehensive investigation in eastern China. Environment International. 2013;61:1-7
  38. 38. Zhu YG, Johnson TA, Su JQ, Qiao M, Guo GX, Stedtfeld RD, Hashsham SA, Tiedje JM. Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proceedings of the National Academy of Sciences. 2013;110(9):3435-3440
  39. 39. Kazimierczak KA, Scott KP, Kelly D, Aminov RI. Tetracycline resistome of the organic pig gut. Applied and Environmental Microbiology. 2009;75(6):1717-1722
  40. 40. Hu Y, Yang X, Lu N, Zhu B. The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal. Gut Microbes. 2014;5(2):245-249
  41. 41. Hu Y, Yang X, Qin J, Lu N, Cheng G, Wu N, Pan Y, Li J, Zhu L, Wang X, Meng Z. Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nature Communications. 2013;4:2151
  42. 42. Forslund K, Sunagawa S, Kultima JR, Mende DR, Arumugam M, Typas A, Bork P. Country-specific antibiotic use practices impact the human gut resistome. Genome Research. 2013;23(7):1163-1169
  43. 43. Ghosh TS, Gupta SS, Nair GB, Mande SS. In silico analysis of antibiotic resistance genes in the gut microflora of individuals from diverse geographies and age-groups. PLoS One. 2013;8(12):e83823
  44. 44. Bengtsson-Palme J, Angelin M, Huss M, Kjellqvist S, Kristiansson E, Palmgren H, Larsson DJ, Johansson A. The human gut microbiome as a transporter of antibiotic resistance genes between continents. Antimicrobial Agents and Chemotherapy. 2015;59(10):6551-6560
  45. 45. Arnold KE, Williams NJ, Bennett M. Disperse abroad in the land’: The role of wildlife in the dissemination of antimicrobial resistance. Biology Letters. 2016;12(8):20160137
  46. 46. Buelow E,Gonzalez TB, Versluis D, Oostdijk EA, Ogilvie LA, van Mourik MS, Oosterink E, van Passel MW, Smidt H, D’andrea MM, de Been M. Effects of selective digestive decontamination (SDD) on the gut resistome. Journal of Antimicrobial Chemotherapy. 2014;69(8):2215-2223
  47. 47. Pérez-Cobas AE, Artacho A, Knecht H, Ferrús ML, Friedrichs A, Ott SJ, Moya A, Latorre A, Gosalbes MJ. Differential effects of antibiotic therapy on the structure and function of human gut microbiota. PLoS One. 2013;8(11):e80201
  48. 48. Forslund K, Sunagawa S, Coelho LP, Bork P. Metagenomic insights into the human gut resistome and the forces that shape it. BioEssays. 2014;36(3):316-329
  49. 49. Raymond F, Ouameur AA, Déraspe M, Iqbal N, Gingras H, Dridi B, Leprohon P, Plante PL, Giroux R, Bérubé È, Frenette J. The initial state of the human gut microbiome determines its reshaping by antibiotics. The ISME Journal. 2016;10(3):707
  50. 50. Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 2010;5(3):e9836
  51. 51. Imchen M, Kumavath R. Vaccination to Combat as an Approach to Reduce the Antibacterial Resistance..! International Journal of Vaccines and Vaccination. 2017;4(1): 00074. DOI: 10.15406/ijvv.2017.04.00074
  52. 52. Kale-Pradhan PB, Jassaly HK, Wilhelm SM. Role of lactobacillus in the prevention of antibiotic-associated diarrhea: A meta-analysis. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2010;30(2):119-126
  53. 53. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. Journal of Clinical Gastroenterology. 2010;44(5):354-360
  54. 54. Lee CR, Cho IH, Jeong BC, Lee SH. Strategies to minimize antibiotic resistance. International Journal of Environmental Research and Public Health. 2013;10(9):4274-4305
  55. 55. Deehan EC, Walter J. The fiber gap and the disappearing gut microbiome: Implications for human nutrition. Trends in Endocrinology & Metabolism. 2016;27(5):239-242
  56. 56. Logan AC, Jacka FN, Prescott SL. Immune-microbiota interactions: Dysbiosis as a global health issue. Current Allergy and Asthma Reports. 2016;16(2):13
  57. 57. Salyers AA, Gupta A, Wang Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends in Microbiology. 2004;12(9):412-416
  58. 58. Gibson MK, Crofts TS, Dantas G. Antibiotics and the developing infant gut microbiota and resistome. Current Opinion in Microbiology. 2015;27:51-56
  59. 59. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Rodriguez JGZ. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158(4):705-721
  60. 60. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222
  61. 61. La Rosa PS, Warner BB, Zhou Y, Weinstock GM, Sodergren E, Hall-Moore CM, Stevens HJ, Bennett WE, Shaikh N, Linneman LA, Hoffmann JA. Patterned progression of bacterial populations in the premature infant gut. Proceedings of the National Academy of Sciences. 2014;111(34):12522-12527
  62. 62. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biology. 2007;5(7):e177
  63. 63. Alicea-Serrano AM, Contreras M, Magris M, Hidalgo G, Dominguez-Bello MG. Tetracycline resistance genes acquired at birth. Archives of Microbiology. 2013;195(6):447-451
  64. 64. Moore AM, Patel S, Forsberg KJ, Wang B, Bentley G, Razia Y, Qin X, Tarr PI, Dantas G. Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes. PLoS One. 2013;8(11):e78822
  65. 65. Arboleya S, Sánchez B, Milani C, Duranti S, Solís G, Fernández N, Clara G, Ventura M, Margolles A, Gueimonde M. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. The Journal of Pediatrics. 2015;166(3):538-544
  66. 66. Bennet R, Eriksson M, Nord CE, ZetterstrÖm R. Fecal bacterial microflora of newborn infants during intensive care management and treatment with five antibiotic regimens. The Pediatric Infectious Disease Journal. 1986;5(5):533-539
  67. 67. Tanaka S, Kobayashi T, Songjinda P, Tateyama A, Tsubouchi M, Kiyohara C, Shirakawa T, Sonomoto K, Nakayama J. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunology & Medical Microbiology. 2009;56(1):80-87
  68. 68. Makino H, Kushiro A, Ishikawa E, Kubota H, Gawad A, Sakai T, Oishi K, Martin R, Ben-Amor K, Knol J, Tanaka R. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant’s microbiota. PLoS One. 2013;8(11):e78331
  69. 69. Abrahamsson TR, Rautava S, Moore AM, Neu J, Sherman PM. The time for a confirmative necrotizing enterocolitis probiotics prevention trial in the extremely low birth weight infant in North America is now! The Journal of Pediatrics. 2014;165(2):389-394
  70. 70. Härtel C, Pagel J, Rupp J, Bendiks M, Guthmann F, Rieger-Fackeldey E, Heckmann M, Franz A, Schiffmann JH, Zimmermann B, Hepping N. Prophylactic use of lactobacillus acidophilus/Bifidobacterium infantis probiotics and outcome in very low birth weight infants. The Journal of Pediatrics. 2014;165(2):285-289
  71. 71. Jones RM, Luo L, Ardita CS, Richardson AN, Kwon YM, Mercante JW, Alam A, Gates CL, Wu H, Swanson PA, Lambeth JD. Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species. The EMBO Journal. 2013;32(23):3017-3028
  72. 72. Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, Li Y, Xia Y, Xie H, Zhong H, Khan MT. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host & Microbe. 2015;17(5):690-703
  73. 73. Dominguez-Bello MG, Costello EK, 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. Proceedings of the National Academy of Sciences. 2010;107(26):11971-11975
  74. 74. Moore AM, Ahmadi S, Patel S, Gibson MK, Wang B, Ndao IM, Deych E, Shannon W, Tarr PI, Warner BB, Dantas G. Gut resistome development in healthy twin pairs in the first year of life. Microbiome. 2015;3(1):27
  75. 75. Lozoff B, Brittenham GM, Wolf AW, McClish DK, Kuhnert PM, Jimenez E, Jimenez R, Mora LA, Gomez I, Krauskoph D. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics. 1987;79(6):981-995
  76. 76. Wang WL, Xu SY, Ren ZG, Tao L, Jiang JW, Zheng SS. Application of metagenomics in the human gut microbiome. World journal of gastroenterology: WJG. 2015;21(3):803
  77. 77. Sommer MO, Dantas G, Church GM. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science. 2009;325(5944):1128-1131

Written By

Madangchanok Imchen and Ranjith Kumavath

Submitted: 08 July 2017 Reviewed: 05 March 2018 Published: 09 May 2018