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Breastfeeding May Help Protect Babies from Antibiotic-Resistant Bacteria

    Bacteria Bifidobacterium, gram-positive anaerobic rod-shaped bacteria which are part of normal flora of human intestine are used as probiotics and in yoghurt production. 3D illustration

    Written by: Sandeep Ravindran, Ph.D. | Issue # 82 | 2019

    • Antibiotic resistance is a major global public health challenge, and more than 200,000 infants are estimated to die every year due to resistant infections.
    • A new study assessed how the milk and gut microbiota of mothers shape the antibiotic resistance of bacteria in the infant gut.
    • The study found that breastfeeding reduced the amount of antibiotic-resistant bacteria in the infant gut, whereas antibiotic treatment of mothers during delivery increased the amount of antibiotic-resistant bacteria.

    Bacterial resistance to antibiotics poses a major challenge to global public health [1,2]. Babies lack a fully developed immune system and gut microbiome, and are particularly susceptible to infections by resistant bacteria [3–5]. More than 200,000 infants are estimated to die every year due to septic infections caused by antibiotic-resistant pathogens [4].

    Bacteria often develop antibiotic resistance by receiving antibiotic resistance genes from other bacteria [6]. The infant gut microbiota has been shown to contain a high abundance of antibiotic resistance genes compared with adults [7–9]. “Infants carried a larger proportion of antibiotic-resistant bacteria in their gut than did adults, despite never having been treated with antibiotics,” says Katariina Pärnänen, a Ph.D. student in Marko Virta’s laboratory at the University of Helsinki.

    This raises the question of where the antibiotic resistance genes in the infant gut originate, with some previous studies suggesting that they are shared between the guts of mothers and infants [10,11]. Another possibility is that antibiotic resistance genes are present in human milk, which is known to influence the infant gut microbiota [12-14].

    In a new study, Pärnänen and her colleagues set out to investigate the origins of antibiotic resistance genes in the infant gut [15]. They sequenced DNA from the milk and gut of 16 mother-infant pairs over a period of 8 months to assess how the milk and gut microbiota of mothers shape the antibiotic resistance of bacteria in the infant gut.

    “The biggest challenge was obtaining enough DNA sequence information from breastmilk to be able to study the antibiotic resistance genes,” says Pärnänen. “This is because breastmilk has a lot of human DNA in it, and when the DNA is sequenced more than 90% of the sequence information is human,” she says. Using the latest DNA sequencing technologies, the researchers were able to sequence sufficient DNA from the milk and gut microbiota to perform their analyses.

    “We could observe that mothers transmit some of the antibiotic-resistant bacteria found in their gut to their infants, so past use of antibiotics of the mother might have an impact on which resistant bacteria end up in the infant gut,” says Pärnänen.

    The researchers also found that antibiotic resistance genes could be transferred through human milk to the infant gut. “Antibiotic resistance genes, which confer resistance to antibiotics in bacteria, were found in breast milk and thus are also likely transmitted to the infant,” says Pärnänen.

    “However, infants who were breastfed until the age of six months had less antibiotic resistance genes in their gut bacteria than infants who weren’t breastfed at all or whose breastfeeding had been terminated earlier,” she says. As a result, breastfeeding seemed to protect infants from resistant bacteria.

    “This is likely because breastmilk promotes the growth of beneficial probiotic bacteria like bifidobacteria, which take over so that bacteria that often carry antibiotic resistance genes cannot grow efficiently,” says Pärnänen. “It is known that bacteria like Escherichia coli are more abundant in infants who are fed formula compared to breastfed infants, and E. coli is often associated with antibiotic resistance and many strains are also pathogenic,” she says. Indeed, a recent study by a different research group showed that high levels of Bifidobacterium in the infant gut microbiome are associated with significantly reduced levels of antimicrobial resistance in early life [16].

    Mothers may need to receive antibiotic treatment during delivery—known as intrapartum antibiotic prophylaxis (IAP)—for various reasons, including to prevent the transmission of harmful bacteria living in the birth canal to the infant during delivery. Pärnänen and her colleagues evaluated the effect of IAP on the development of the infant gut microbiome and the transmission of antibiotic resistance genes.

    “We saw that intrapartum antibiotic prophylaxis treatment given to mothers increased the abundance of antibiotic resistance genes in the infant gut even six months after treatment,” says Pärnänen.

    The researchers hypothesized that antibiotics administered during delivery to the mother might eliminate all bacteria except those resistant to the drug, and the mother was likely to pass these resistant bacteria on to her child where they had a head start in establishing the infant gut microbiome.

    Pärnänen is planning follow-up studies to investigate other factors that might influence antibiotic resistance in the infant gut. “Next I am planning to look more closely at the influence of different diets on antibiotic resistance of infant gut bacteria,” she says.

    The researchers conclude that the number of antibiotic resistance genes present in the infant gut is influenced by factors that shape the overall infant gut microbiome, including the duration of breastfeeding and antibiotic treatment of mothers during delivery. The results suggest that mothers contribute to the antibiotic resistance genes in the infant gut microbiota by sharing genes from their gut and breast milk bacteria.

    The study also adds to the known health benefits of exclusive breastfeeding for at least six months [17]. “We suggest that breastfeeding should be promoted not only for its other health benefits, but also for the reason that it has the potential to reduce the abundance of antibiotic-resistant bacteria in the infant gut,” says Pärnänen.

    References

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    10. Gosalbes M.J., Vallès Y., Jiménez-Hernández N., Balle C., Riva P., Miravet-Verde S., de Vries L.E., Llop S., Agersø Y., Sørensen S.J., Ballester F., Francino M.P. High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples. J Dev Orig Health Dis. 2016 Feb;7(1):35-44.

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    12. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012 Sep;22(9):1147-62.

    13. Jost T., Lacroix C., Braegger C.P., Rochat F., Chassard C. Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environ Microbiol. 2014 Sep;16(9):2891-904.

    14. Rahman S.F., Olm M.R., Morowitz M.J., Banfield J.F. Machine learning leveraging genomes from metagenomes identifies influential antibiotic resistance genes in the infant gut microbiome. mSystems. 2018 Jan 9;3(1). pii: e00123-17.

    15. Pärnänen K., Karkman A., Hultman J., Lyra C., Bengtsson-Palme J., Larsson D.G.J., Rautava S., Isolauri E., Salminen S., Kumar H., Satokari R., Virta M. Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nat Commun. 2018 Sep 24;9(1):3891.

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