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Human Milk Microbiota: Transferring the Antibiotic Resistome to Infants

  • Lahari DasEmail author
  • Richa Virmani
  • Vishal Sharma
  • Deepti Rawat
  • Yogendra SinghEmail author
Review article
  • 32 Downloads

Abstract

Commensal bacterial population is believed to be a reservoir for antibiotic resistance genes (ARGs). The infant gut microbiota has relatively higher abundance of ARGs than the adults. These genes can get transferred from commensals to pathogens by horizontal gene transfer, which magnifies the spectrum of antibiotic resistance in the environment. The presence of ARGs in neo-nates and infants, with no prior antibiotic exposure, questions their origin in the naïve commensal population. Breast milk microbiota that is responsible for the initial seeding of infant gut microbiota has also been found to harbour a vast array of ARGs. This review discusses the recent findings that indicate the potential of breast milk microbiota to act as a vehicle for transmission of ARGs to infants.

Keywords

Antibiotic resistance Resistome Breast milk microbiota Infant gut microbiota Antibiotic resistance genes 

Notes

Acknowledgement

UGC-D. S. Kothari Post-doctoral fellowship to LD and CSIR Junior research fellowship to VS are duly acknowledged.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ballard O, Morrow AL (2013) Human milk composition: nutrients and bioactive factors. Pediatr Clin N Am 60:49–74.  https://doi.org/10.1016/j.pcl.2012.10.002 CrossRefGoogle Scholar
  2. 2.
    Le Doare K, Holder B, Bassett A, Pannaraj PS (2018) Mother’s milk: a purposeful contribution to the development of the infant microbiota and immunity. Front Immunol 9:361.  https://doi.org/10.3389/fimmu.2018.00361 CrossRefGoogle Scholar
  3. 3.
    Toscano M, De Grandi R, Grossi E, Drago L (2017) Role of the human breast milk-associated microbiota on the newborns’ immune system: a mini review. Front Microbiol 8:2100.  https://doi.org/10.3389/fmicb.2017.02100 CrossRefGoogle Scholar
  4. 4.
    Murphy K, Curley D, O’Callaghan TF, O’Shea CA, Dempsey EM, O’Toole PW, Ross RP, Ryan CA, Stanton C (2017) The composition of human milk and infant faecal microbiota over the first three months of life: a pilot study. Sci Rep 7:40597.  https://doi.org/10.1038/srep40597 CrossRefGoogle Scholar
  5. 5.
    Lonnerdal B (2016) Bioactive proteins in human milk: health, nutrition, and implications for infant formulas. J Pediatr 173:S4–S9.  https://doi.org/10.1016/j.jpeds.2016.02.070 CrossRefGoogle Scholar
  6. 6.
    Blanton LV, Charbonneau MR, Salih T, Barratt MJ, Venkatesh S, Ilkaveya O, Subramanian S, Manary MJ, Trehan I, Jorgensen JM, Fan YM, Henrissat B, Leyn SA, Rodionov DA, Osterman AL, Maleta KM, Newgard CB, Ashorn P, Dewey KG, Gordon JI (2016) Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science 351:aad3311.  https://doi.org/10.1126/science.aad3311 CrossRefGoogle Scholar
  7. 7.
    Diaz Heijtz R (2016) Fetal, neonatal, and infant microbiome: perturbations and subsequent effects on brain development and behavior. Semin Fetal Neonatal Med 21:410–417.  https://doi.org/10.1016/j.siny.2016.04.012 CrossRefGoogle Scholar
  8. 8.
    Oddy WH (2017) Breastfeeding, childhood asthma, and allergic disease. Ann Nutr Metab 70:26–36.  https://doi.org/10.1159/000457920 CrossRefGoogle Scholar
  9. 9.
    Penders J, Stobberingh EE, Savelkoul PH, Wolffs PF (2013) The human microbiome as a reservoir of antimicrobial resistance. Front Microbiol 4:87.  https://doi.org/10.3389/fmicb.2013.00087 CrossRefGoogle Scholar
  10. 10.
    Ruiz L, Garcia-Carral C, Rodriguez JM (2019) Unfolding the human milk microbiome landscape in the omics era. Front Microbiol 10:1378.  https://doi.org/10.3389/fmicb.2019.01378 CrossRefGoogle Scholar
  11. 11.
    Ruiz L, Bacigalupe R, Garcia-Carral C, Boix-Amoros A, Arguello H, Silva CB, de Los Angeles Checa M, Mira A, Rodriguez JM (2019) Microbiota of human precolostrum and its potential role as a source of bacteria to the infant mouth. Sci Rep 9:8435.  https://doi.org/10.1038/s41598-019-42514-1 CrossRefGoogle Scholar
  12. 12.
    Rodriguez JM (2014) The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr 5:779–784.  https://doi.org/10.3945/an.114.007229 CrossRefGoogle Scholar
  13. 13.
    Biagi E, Quercia S, Aceti A, Beghetti I, Rampelli S, Turroni S, Faldella G, Candela M, Brigidi P, Corvaglia L (2017) The bacterial ecosystem of mother’s milk and infant’s mouth and gut. Front Microbiol 8:1214.  https://doi.org/10.3389/fmicb.2017.01214 CrossRefGoogle Scholar
  14. 14.
    Kumar H, du Toit E, Kulkarni A, Aakko J, Linderborg KM, Zhang Y, Nicol MP, Isolauri E, Yang B, Collado MC, Salminen S (2016) Distinct patterns in human milk microbiota and fatty acid profiles across specific geographic locations. Front Microbiol 7:1619.  https://doi.org/10.3389/fmicb.2016.01619 Google Scholar
  15. 15.
    Hunt KM, Foster JA, Forney LJ, Schutte UM, Beck DL, Abdo Z, Fox LK, Williams JE, McGuire MK, McGuire MA (2011) Characterization of the diversity and temporal stability of bacterial communities in human milk. PLoS ONE 6:e21313.  https://doi.org/10.1371/journal.pone.0021313 CrossRefGoogle Scholar
  16. 16.
    Cabrera-Rubio R, Mira-Pascual L, Mira A, Collado MC (2016) Impact of mode of delivery on the milk microbiota composition of healthy women. J Dev Orig Health Dis 7:54–60.  https://doi.org/10.1017/s2040174415001397 CrossRefGoogle Scholar
  17. 17.
    Lackey KA, Williams JE, Meehan CL, Zachek JA, Benda ED, Price WJ, Foster JA, Sellen DW, Kamau-Mbuthia EW, Kamundia EW, Mbugua S, Moore SE, Prentice AM, Debela Gindola K, Kvist LJ, Otoo GE, Garcia-Carral C, Jimenez E, Ruiz L, Rodriguez JM, Pareja RG, Bode L, McGuire MA, McGuire MK (2019) What’s normal? Microbiomes in human milk and infant feces are related to each other but vary geographically: the INSPIRE study. Front Nutr 6:45.  https://doi.org/10.3389/fnut.2019.00045 CrossRefGoogle Scholar
  18. 18.
    Hermansson H, Kumar H, Collado MC, Salminen S, Isolauri E, Rautava S (2019) Breast milk microbiota is shaped by mode of delivery and intrapartum antibiotic exposure. Front Nutr 6:4.  https://doi.org/10.3389/fnut.2019.00004 CrossRefGoogle Scholar
  19. 19.
    Bag S, Ghosh TS, Banerjee S, Mehta O, Verma J, Dayal M, Desigamani A, Kumar P, Saha B, Kedia S, Ahuja V, Ramamurthy T, Das B (2019) Molecular insights into antimicrobial resistance traits of commensal human gut microbiota. Microb Ecol 77:546–557.  https://doi.org/10.1007/s00248-018-1228-7 CrossRefGoogle Scholar
  20. 20.
    Moore AM, Patel S, Forsberg KJ, Wang B, Bentley G, Razia Y, Qin X, Tarr PI, Dantas G (2013) Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes. PLoS ONE 8:e78822.  https://doi.org/10.1371/journal.pone.0078822 CrossRefGoogle Scholar
  21. 21.
    von Wintersdorff CJ, Penders J, van Niekerk JM, Mills ND, Majumder S, van Alphen LB, Savelkoul PH, Wolffs PF (2016) Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Front Microbiol 7:173.  https://doi.org/10.3389/fmicb.2016.00173 Google Scholar
  22. 22.
    Casals-Pascual C, Vergara A, Vila J (2018) Intestinal microbiota and antibiotic resistance: perspectives and solutions. Hum Microbiome J 9:11–15.  https://doi.org/10.1016/j.humic.2018.05.002 CrossRefGoogle Scholar
  23. 23.
    Lerner A, Matthias T, Aminov R (2017) Potential effects of horizontal gene exchange in the human gut. Front Immunol 8:1630.  https://doi.org/10.3389/fimmu.2017.01630 CrossRefGoogle Scholar
  24. 24.
    Canton R, Morosini MI (2011) Emergence and spread of antibiotic resistance following exposure to antibiotics. FEMS Microbiol Rev 35:977–991.  https://doi.org/10.1111/j.1574-6976.2011.00295.x CrossRefGoogle Scholar
  25. 25.
    Davies J, Davies D (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74:417–433.  https://doi.org/10.1128/mmbr.00016-10 CrossRefGoogle Scholar
  26. 26.
    Gumpert H, Kubicek-Sutherland JZ, Porse A, Karami N, Munck C, Linkevicius M, Adlerberth I, Wold AE, Andersson DI, Sommer MOA (2017) Transfer and persistence of a multi-drug resistance plasmid in situ of the infant gut microbiota in the absence of antibiotic treatment. Front Microbiol 8:1852.  https://doi.org/10.3389/fmicb.2017.01852 CrossRefGoogle Scholar
  27. 27.
    Fouhy F, Ogilvie LA, Jones BV, Ross RP, Ryan AC, Dempsey EM, Fitzgerald GF, Stanton C, Cotter PD (2014) Identification of aminoglycoside and beta-lactam resistance genes from within an infant gut functional metagenomic library. PLoS ONE 9:e108016.  https://doi.org/10.1371/journal.pone.0108016 CrossRefGoogle Scholar
  28. 28.
    Duranti S, Lugli GA, Mancabelli L, Turroni F, Milani C, Mangifesta M, Ferrario C, Anzalone R, Viappiani A, van Sinderen D, Ventura M (2017) Prevalence of antibiotic resistance genes among human gut-derived bifidobacteria. Appl Environ Microbiol 83:e02894-16.  https://doi.org/10.1128/aem.02894-16 CrossRefGoogle Scholar
  29. 29.
    Ravi A, Valdes-Varela L, Gueimonde M, Rudi K (2018) Transmission and persistence of IncF conjugative plasmids in the gut microbiota of full-term infants. FEMS Microbiol Ecol 94:fix158.  https://doi.org/10.1093/femsec/fix158 CrossRefGoogle Scholar
  30. 30.
    Saksena R, Gaind R, Sinha A, Kothari C, Chellani H, Deb M (2018) High prevalence of fluoroquinolone resistance amongst commensal flora of antibiotic naive neonates: a study from India. J Med Microbiol 67:481–488.  https://doi.org/10.1099/jmm.0.000686 CrossRefGoogle Scholar
  31. 31.
    Ravi A, Avershina E, Foley SL, Ludvigsen J, Storro O, Oien T, Johnsen R, McCartney AL, L’Abee-Lund TM, Rudi K (2015) The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons. Sci Rep 5:15317.  https://doi.org/10.1038/srep15317 CrossRefGoogle Scholar
  32. 32.
    Pannaraj PS, Li F, Cerini C, Bender JM, Yang S, Rollie A, Adisetiyo H, Zabih S, Lincez PJ, Bittinger K, Bailey A, Bushman FD, Sleasman JW, Aldrovandi GM (2017) Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr 171:647–654.  https://doi.org/10.1001/jamapediatrics.2017.0378 CrossRefGoogle Scholar
  33. 33.
    Huang MS, Cheng CC, Tseng SY, Lin YL, Lo HM, Chen PW (2019) Most commensally bacterial strains in human milk of healthy mothers display multiple antibiotic resistance. Microbiologyopen 8:e00618.  https://doi.org/10.1002/mbo3.618 CrossRefGoogle Scholar
  34. 34.
    Chen PW, Tseng SY, Huang MS (2016) Antibiotic susceptibility of commensal bacteria from human milk. Curr Microbiol 72:113–119.  https://doi.org/10.1007/s00284-015-0925-4 CrossRefGoogle Scholar
  35. 35.
    Ojo-Okunola A, Nicol M, du Toit E (2018) Human breast milk bacteriome in health and disease. Nutrients 10:e1643.  https://doi.org/10.3390/nu10111643 CrossRefGoogle Scholar
  36. 36.
    Marin M, Arroyo R, Espinosa-Martos I, Fernandez L, Rodriguez JM (2017) Identification of emerging human mastitis pathogens by MALDI-TOF and assessment of their antibiotic resistance patterns. Front Microbiol 8:1258.  https://doi.org/10.3389/fmicb.2017.01258 CrossRefGoogle Scholar
  37. 37.
    Hudelson SE, McConnell MS, Bagenda D, Piwowar-Manning E, Parsons TL, Nolan ML, Bakaki PM, Thigpen MC, Mubiru M, Fowler MG, Eshleman SH (2010) Emergence and persistence of nevirapine resistance in breast milk after single-dose nevirapine administration. AIDS 24:557–561.  https://doi.org/10.1097/QAD.0b013e3283346e60 CrossRefGoogle Scholar
  38. 38.
    Kozak K, Charbonneau D, Sanozky-Dawes R, Klaenhammer T (2015) Characterization of bacterial isolates from the microbiota of mothers’ breast milk and their infants. Gut Microbes 6:341–351.  https://doi.org/10.1080/19490976.2015.1103425 CrossRefGoogle Scholar
  39. 39.
    Pärnänen K, Karkman A, Hultman J, Lyra C, Bengtsson-Palme J, Larsson DGJ, Rautava S, Isolauri E, Salminen S, Kumar H, Satokari R, Virta M (2018) Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nat Commun 9:3891.  https://doi.org/10.1038/s41467-018-06393-w CrossRefGoogle Scholar
  40. 40.
    Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (2010) Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 35:322–332.  https://doi.org/10.1016/j.ijantimicag.2009.12.011 CrossRefGoogle Scholar
  41. 41.
    Ahmed MN, Porse A, Sommer MOA, Hoiby N, Ciofu O (2018) Evolution of antibiotic resistance in biofilm and planktonic Pseudomonas aeruginosa populations exposed to subinhibitory levels of ciprofloxacin. Antimicrob Agents Chemother 62:e00320-18.  https://doi.org/10.1128/aac.00320-18 CrossRefGoogle Scholar
  42. 42.
    Virmani R, Hasija Y, Singh Y (2018) Effect of homocysteine on biofilm formation by mycobacteria. Indian J Microbiol 58:287–293.  https://doi.org/10.1007/s12088-018-0739-8 CrossRefGoogle Scholar
  43. 43.
    Das L, Singh Y (2018) Quorum sensing inhibition: a target for treating chronic wounds. In: Kalia VC (ed) Biotechnological applications of quorum sensing inhibitors. Springer, Singapore, pp 111–126CrossRefGoogle Scholar
  44. 44.
    Partridge SR, Kwong SM, Firth N, Jensen SO (2018) Mobile genetic elements associated with antimicrobial resistance. Clin Microbiol Rev 31:e00088-17.  https://doi.org/10.1128/cmr.00088-17 CrossRefGoogle Scholar
  45. 45.
    Dubey GP, Ben-Yehuda S (2011) Intercellular nanotubes mediate bacterial communication. Cell 144:590–600.  https://doi.org/10.1016/j.cell.2011.01.015 CrossRefGoogle Scholar
  46. 46.
    Dzidic M, Boix-Amoros A, Selma-Royo M, Mira A, Collado MC (2018) Gut microbiota and mucosal immunity in the neonate. Med Sci 6:e56.  https://doi.org/10.3390/medsci6030056 Google Scholar
  47. 47.
    Lazar V, Ditu LM, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, Picu A, Petcu L, Chifiriuc MC (2018) Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer. Front Immunol 9:1830.  https://doi.org/10.3389/fimmu.2018.01830 CrossRefGoogle Scholar
  48. 48.
    Libertucci J, Young VB (2019) The role of the microbiota in infectious diseases. Nat Microbiol 4:35–45.  https://doi.org/10.1038/s41564-018-0278-4 CrossRefGoogle Scholar
  49. 49.
    Maji A, Misra R, Dhakan DB, Gupta V, Mahato NK, Saxena R, Mittal P, Thukral N, Sharma E, Singh A, Virmani R, Gaur M, Singh H, Hasija Y, Arora G, Agrawal A, Chaudhry A, Khurana JP, Sharma VK, Lal R, Singh Y (2018) Gut microbiome contributes to impairment of immunity in pulmonary tuberculosis patients by alteration of butyrate and propionate producers. Environ Microbiol 20:402–419.  https://doi.org/10.1111/1462-2920.14015 CrossRefGoogle Scholar
  50. 50.
    Sood U, Bajaj A, Kumar R, Khurana S, Kalia VC (2018) Infection and microbiome: impact of tuberculosis on human gut microbiome of indian cohort. Indian J Microbiol 58:123–125.  https://doi.org/10.1007/s12088-018-0706-4 CrossRefGoogle Scholar
  51. 51.
    D’Argenio V (2018) The prenatal microbiome: a new player for human health. High Throughput 7:e38.  https://doi.org/10.3390/ht7040038 CrossRefGoogle Scholar
  52. 52.
    Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, Li Y, Xia Y, Xie H, Zhong H, Khan MT, Zhang J, Li J, Xiao L, Al-Aama J, Zhang D, Lee YS, Kotowska D, Colding C, Tremaroli V, Yin Y, Bergman S, Xu X, Madsen L, Kristiansen K, Dahlgren J, Wang J (2015) Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17:690–703.  https://doi.org/10.1016/j.chom.2015.04.004 CrossRefGoogle Scholar
  53. 53.
    Matuszkiewicz-Rowinska J, Malyszko J, Wieliczko M (2015) Urinary tract infections in pregnancy: old and new unresolved diagnostic and therapeutic problems. Arch Med Sci 11:67–77.  https://doi.org/10.5114/aoms.2013.39202 CrossRefGoogle Scholar
  54. 54.
    Bromiker R, Ernest N, Meir MB, Kaplan M, Hammerman C, Schimmel MS, Schlesinger Y (2013) Correlation of bacterial type and antibiotic sensitivity with maternal antibiotic exposure in early-onset neonatal sepsis. Neonatology 103:48–53.  https://doi.org/10.1159/000342215 CrossRefGoogle Scholar
  55. 55.
    Liu R, Lin L, Wang D (2016) Antimicrobial prophylaxis in caesarean section delivery. Exp Ther Med 12:961–964.  https://doi.org/10.3892/etm.2016.3350 CrossRefGoogle Scholar

Copyright information

© Association of Microbiologists of India 2019

Authors and Affiliations

  1. 1.Department of ZoologyUniversity of DelhiDelhiIndia

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