Skip to main content Accessibility help

High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples

  • M. J. Gosalbes (a1) (a2), Y. Vallès (a1), N. Jiménez-Hernández (a1), C. Balle (a3), P. Riva (a1), S. Miravet-Verde (a1), L. E. de Vries (a3) (a4), S. Llop (a2) (a5), Y. Agersø (a6), S. J. Sørensen (a3), F. Ballester (a2) (a5) and M. P. Francino (a1) (a2) (a7)...


The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to β-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies’ mothers, as well as a mother–infant series including meconium, fecal samples collected through the infant’s 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds’ samples a particularly elevated prevalence of mecA (>45%), six-fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant’s GIT as a noteworthy reservoir of this gene.


Corresponding author

*Address for correspondence: M. P. Francino, Unitat Mixta d’Investigació en Genòmica i Salut, FISABIO-Salut Pública, Ave. Catalunya 21, Valencia 46020, Spain. (Email


Hide All
1. Salyers, AA, Gupta, A, Wang, Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol. 2004; 12, 412416.
2. Seville, LA, Patterson, AJ, Scott, KP, et al. Distribution of tetracycline and erythromycin resistance genes among human oral and fecal metagenomic DNA. Microb Drug Resist. 2009; 15, 159166.
3. Sommer, MO, Dantas, G, Church, GM. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science. 2009; 325, 11281131.
4. Moore, AM, Patel, S, Forsberg, KJ, et al. Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes. PLoS One. 2013; 8, e78822.
5. Fouhy, F, Ogilvie, LA, Jones, BV, et al. Identification of aminoglycoside and beta-lactam resistance genes from within an infant gut functional metagenomic library. PLoS One. 2014; 9, e108016.
6. Lu, N, Hu, Y, Zhu, L, et al. DNA microarray analysis reveals that antibiotic resistance-gene diversity in human gut microbiota is age related. Sci Rep. 2014; 4, 4302.
7. 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, 245249.
8. Gueimonde, M, Salminen, S, Isolauri, E. Presence of specific antibiotic (tet) resistance genes in infant faecal microbiota. FEMS Immunol Med Microbiol. 2006; 48, 2125.
9. Mitsou, EK, Kirtzalidou, E, Pramateftaki, P, Kyriacou, A. Antibiotic resistance in faecal microbiota of greek healthy infants. Benef Microbes. 2010; 1, 297306.
10. de Vries, LE, Valles, Y, Agerso, Y, et al. The gut as reservoir of antibiotic resistance: microbial diversity of tetracycline resistance in mother and infant. PLoS One. 2011; 6, e21644.
11. Zhang, L, Kinkelaar, D, Huang, Y, et al.. Acquired antibiotic resistance: are we born with it? Appl Environ Microbiol. 2011; 77, 71347141.
12. Alicea-Serrano, AM, Contreras, M, Magris, M, Hidalgo, G, Dominguez-Bello, MG. Tetracycline resistance genes acquired at birth. Arch Microbiol. 2013; 195, 447451.
13. Collado, MC, Isolauri, E, Laitinen, K, Salminen, S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008; 88, 894899.
14. Gilbert, SF. A holobiont birth narrative: the epigenetic transmission of the human microbiome. Front Genet. 2014; 5, 282.
15. Koren, O, Goodrich, JK, Cullender, TC, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012; 150, 470480.
16. Berg, R. Bacterial translocation from the gastrintestinal tract. Trends Microbiol. 1995; 3, 149154.
17. Cani, PD, Delzenne, NM. The gut microbiome as therapeutic target. Pharmacol Ther. 2011; 130, 202212.
18. Francino, MP. Early development of the gut microbiota and immune health. Pathogens. 2014; 3, 769790.
19. Gosalbes, MJ, Llop, S, Valles, Y, et al. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Exp Allergy. 2013; 43, 198211.
20. Valles, Y, Artacho, A, Pascual-Garcia, A, et al. Microbial succession in the gut: directional trends of taxonomic and functional change in a birth cohort of Spanish infants. PLoS Genet. 2014; 10, e1004406.
21. Perez, PF, Dore, J, Leclerc, M, et al.. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics. 2007; 119, e724e732.
22. Donnet-Hughes, A, Perez, PF, Dore, J, et al. Potential role of the intestinal microbiota of the mother in neonatal immune education. Proc Nutr Soc. 2010; 69, 407415.
23. Amar, J, Chabo, C, Waget, A, et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med. 2011; 3, 559572.
24. McGovern, N, Chan, JK, Ginhoux, F. Dendritic cells in humans – from fetus to adult. Int Immunol. 2015; 27, 6572.
25. DiGiulio, DB, Romero, R, Amogan, HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One. 2008; 3, e3056.
26. DiGiulio, DB, Romero, R, Kusanovic, JP, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010; 64, 3857.
27. Dong, Y, St Clair, PJ, Ramzy, I, Kagan-Hallet, KS, Gibbs, RS. A microbiologic and clinical study of placental inflammation at term. Obstet Gynecol. 1987; 70, 175182.
28. Lewis, JF, Johnson, P, Miller, P. Evaluation of amniotic fluid for aerobic and anaerobic bacteria. Am J Clin Pathol. 1976; 65, 5863.
29. Gibbs, RS, Blanco, JD, St Clair, PJ, Castaneda, YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982; 145, 18.
30. Romero, R, Mazor, M, Morrotti, R, et al. Infection and labor. Vii. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term. Am J Obstet Gynecol. 1992; 166, 129133.
31. Romero, R, Sirtori, M, Oyarzun, E, et al. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol. 1989; 161, 817824.
32. Bearfield, C, Davenport, ES, Sivapathasundaram, V, Allaker, RP. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG. 2002; 109, 527533.
33. Steel, JH, Malatos, S, Kennea, N, et al.. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res. 2005; 57, 404411.
34. Jimenez, E, Fernandez, L, Marin, ML, et al.. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005; 51, 270274.
35. Roos, PJ, Malan, AF, Woods, DL, et al. The bacteriological environment of preterm infants. S Afr Med J. 1980; 57, 347350.
36. Stout, MJ, Conlon, B, Landeau, M, et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am J Obstet Gynecol 2013; 208, 226 e221226 e227.
37. Aagaard, K, Ma, J, Antony, KM, et al. The placenta harbors a unique microbiome. Sci Transl Med 2014; 6, 237ra265.
38. Jimenez, E, Marin, ML, Martin, R, et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008; 159, 187193.
39. Koenig, JE, Spor, A, Scalfone, N, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011; 108(Suppl. 1), 45784585.
40. Moles, L, Gomez, M, Heilig, H, et al. Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One. 2013; 8, e66986.
41. Dominguez-Bello, MG, Costello, EK, Contreras, M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010; 107, 1197111975.
42. Hu, J, Nomura, Y, Bashir, A, et al. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS One. 2013; 8, e78257.
43. Madan, JC, Salari, RC, Saxena, D, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012; 97, F456F462.
44. Mshvildadze, M, Neu, J, Shuster, J, et al. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr. 2010; 156, 2025.
45. Valles, Y, Gosalbes, MJ, de Vries, LE, Abellan, JJ, Francino, MP. Metagenomics and development of the gut microbiota in infants. Clin Microbiol Infect. 2012; 18(Suppl. 4), 2126.
46. Cabrera-Rubio, R, Collado, MC, Laitinen, K, et al. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012; 96, 544551.
47. Nichols, DA, Renslo, AR, Chen, Y. Fragment-based inhibitor discovery against beta-lactamase. Fut Med Chem. 2014; 6, 413427.
48. Lowy, FD. Antimicrobial resistance: the example of Staphylococcus aureus . J Clin Invest. 2003; 111, 12651273.
49. Kazimierczak, KA, Scott, KP, Kelly, D, Aminov, RI. Tetracycline resistome of the organic pig gut. Appl Environ Microbiol. 2009; 75, 17171722.
50. Ribas-Fito, N, Ramon, R, Ballester, F, et al. Child health and the environment: the INMA Spanish Study. Paediatr Perinat Epidemiol. 2006; 20, 403410.
51. Ng, LK, Martin, I, Alfa, M, Mulvey, M. Multiplex pcr for the detection of tetracycline resistant genes. Mol Cell Probes. 2001; 15, 209215.
52. Clemente, JC, Pehrsson, EC, Blaser, MJ, et al. The microbiome of uncontacted amerindians. Sci Adv. 2015; 1, e1500183.
53. Agerso, Y, Aarestrup, FM, Pedersen, K, et al. Prevalence of extended-spectrum cephalosporinase (esc)-producing Escherichia coli in danish slaughter pigs and retail meat identified by selective enrichment and association with cephalosporin usage. J Antimicrob Chemother. 2012; 67, 582588.
54. Poirel, L, Walsh, TR, Cuvillier, V, Nordmann, P. Multiplex pcr for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis. 2011; 70, 119123.
55. Mendes, RE, Kiyota, KA, Monteiro, J, et al. Rapid detection and identification of metallo-β-lactamase-encoding genes by multiplex real-time PCR assay and melt curve analysis. J Clin Microbiol. 2007; 45, 544547.
56. Poulsen, AB, Skov, R, Pallesen, LV. Detection of methicillin resistance in coagulase-negative staphylococci and in staphylococci directly from simulated blood cultures using the evigene mrsa detection kit. J Antimicrob Chemother. 2003; 51, 419421.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed