Microbial Ecology

, Volume 78, Issue 2, pp 517–527 | Cite as

Effect of the Nursing Mother on the Gut Microbiome of the Offspring During Early Mouse Development

  • Nicole Simone Treichel
  • Zala Prevoršek
  • Vesna Mrak
  • Matea Kostrić
  • Gisle Vestergaard
  • Bärbel FoeselEmail author
  • Stefan Pfeiffer
  • Blaž Stres
  • Anne Schöler
  • Michael Schloter
Host Microbe Interactions


The development of the gut microbiome is influenced by several factors. It is acquired during and after birth and involves both maternal and environmental factors as well as the genetic disposition of the offspring. However, it is unclear if the microbiome development is directly triggered by the mode of delivery and very early contact with the mother or mostly at later stages of initial development mainly by breast milk provided by the mother. To investigate to what extent the gut microbiome composition of the offspring is determined by the nursing mother, providing breast milk, compared to the birth mother during early development, a cross-fostering experiment involving two genetically different mouse lines was developed, being prone to be obese or lean, respectively. The microbiome of the colon was analyzed by high-throughput 16S rRNA gene sequencing, when the mice were 3 weeks old. The nursing mother affected both α- and β-diversity of the offspring’s gut microbiome and shaped its composition. Especially bacterial families directly transferred by breast milk, like Streptococcaceae, or families which are strongly influenced by the quality of the breast milk like Rikenellaceae, showed a strong response. The core microbiome transferred from the obese nursing mother showed a higher robustness in comparison to the microbiome transferred from the lean nursing mother. Overall, the nursing mother impacts the gut microbial composition of the offspring during early development and might play an important role for health and disease of the animals at later stages of life.


Gut microbiome Obesity Cross-fostering Mice 16S rRNA sequencing Birth mother Nursing mother 



operational taxonomic unit


lean nursing mother


obese nursing mother


lean birth mother


obese birth mother



The authors thank Susanne Kublik (Helmholtz Zentrum München) for technically supporting this work. Simon Horvat (University of Ljubljana) is acknowledged for donation of lean and fat mouse lines.

Authors’ Contributions

ZP, BS, VM, AS, and MS designed the study. NST performed lab work and sequencing. GV and MK established the bioinformatics pipeline based on the open-source software package QIIME and helped with analysis. NST and AS generated and analyzed the sequence data. NST, MS, SP, BF, and AS conceptualized and wrote the manuscript. All authors contributed to revisions and approved the final manuscript.

Compliance with Ethical Standards

Ethics Approval and Consent to Participate

All applicable national guidelines for the care and use of animals, which are all in compliance with the EU regulations, were followed.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

248_2019_1317_MOESM1_ESM.pdf (538 kb)
ESM 1 (PDF 537 kb)


  1. 1.
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1131 CrossRefGoogle Scholar
  2. 2.
    Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BAH, Forslund K, Hildebrand F, Prifti E, Falony G, Le Chatelier E, Levenez F, Doré J, Mattila I, Plichta DR, Pöhö P, Hellgren LI, Arumugam M, Sunagawa S, Vieira-Silva S, Jørgensen T, Holm JB, Trošt K, Consortium M, Kristiansen K, Brix S, Raes J, Wang J, Hansen T, Bork P, Brunak S, Oresic M, Ehrlich SD, Pedersen O (2016) Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535(7612):376–381. CrossRefPubMedGoogle Scholar
  3. 3.
    Ley RE (2010) Obesity and the human microbiome. Curr Opin Gastroenterol 26(1):5–11. CrossRefGoogle Scholar
  4. 4.
    Daniel H, Gholami AM, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, Böhm C, Wenning M, Wagner M, Blaut M, Schmitt-Kopplin P, Kuster B, Haller D, Clavel T (2014) High-fat diet alters gut microbiota physiology in mice. ISME J 8(2):295–308. CrossRefPubMedGoogle Scholar
  5. 5.
    Campbell SC, Wisniewski PJ, Noji M, McGuinness LR, Häggblom MM, Lightfoot SA, Joseph LB, Kerkhof LJ (2016) The effect of diet and exercise on intestinal integrity and microbial diversity in mice. PLoS One 11(3):e0150502. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Goodrich Julia K, Waters Jillian L, Poole Angela C, Sutter Jessica L, Koren O, Blekhman R, Beaumont M, Van Treuren W, Knight R, Bell Jordana T, Spector Timothy D, Clark Andrew G, Ley Ruth E (2014) Human genetics shape the gut microbiome. Cell 159(4):789–799. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, Valero R, Raccah D, Vialettes B, Raoult D (2012) Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes 36(6):817–825 CrossRefGoogle Scholar
  8. 8.
    Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, Costea PI, Godneva A, Kalka IN, Bar N, Shilo S, Lador D, Vila AV, Zmora N, Pevsner-Fischer M, Israeli D, Kosower N, Malka G, Wolf BC, Avnit-Sagi T, Lotan-Pompan M, Weinberger A, Halpern Z, Carmi S, Fu J, Wijmenga C, Zhernakova A, Elinav E, Segal E (2018) Environment dominates over host genetics in shaping human gut microbiota. Nature 555:210–215. CrossRefGoogle Scholar
  9. 9.
    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486(7402):222–227 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    McKnite AM, Perez-Munoz ME, Lu L, Williams EG, Brewer S, Andreux PA, Bastiaansen JWM, Wang X, Kachman SD, Auwerx J, Williams RW, Benson AK, Peterson DA, Ciobanu DC (2012) Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. PLoS One 7(6):e39191. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci 107(26):11971–11975. CrossRefPubMedGoogle Scholar
  12. 12.
    Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R, Rodríguez JM (2013) The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res 69(1):1–10. CrossRefPubMedGoogle Scholar
  13. 13.
    Perez PF, Doré J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segura-Roggero I, Schiffrin EJ, Donnet-Hughes A (2007) Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics 119(3):e724–e732. CrossRefPubMedGoogle Scholar
  14. 14.
    Pantoja-Feliciano IG, Clemente JC, Costello EK, Perez ME, Blaser MJ, Knight R, Dominguez-Bello MG (2013) Biphasic assembly of the murine intestinal microbiota during early development. ISME J 7(6):1112–1115. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sharp GL, Hill WG, Robertson A (1984) Effects of selection on growth, body composition and food intake in mice I. Responses in selected traits. Genet Res 43(1):75–92. CrossRefPubMedGoogle Scholar
  16. 16.
    Horvat S, Bünger L, Falconer VM, Mackay P, Law A, Bulfield G, Keightley PD (2000) Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm Genome 11(1):2–7. CrossRefPubMedGoogle Scholar
  17. 17.
    Bünger L, Forsting J, McDonald KL, Horvat S, Duncan J, Hochscheid S, Baile CA, Hill WG, Speakman JR (2003) Long-term divergent selection on fatness in mice indicates a regulation system independent of leptin production and reception. FASEB J 17(1):85–87. CrossRefPubMedGoogle Scholar
  18. 18.
    Klindworth A, Pruesse E, Schweer T, Peplies J, Quast C, Horn M, Glöckner FO (2012) Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res 41(1):e1–e1. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Magoč T, Salzberg SL (2011) FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27(21):2957–2963. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Schmieder R, Edwards R (2011) Fast identification and removal of sequence contamination from genomic and metagenomic datasets. PLoS One 6(3):e17288. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hansen MA, Oey H, Fernandez-Valverde S, Jung C-H, Mattick JS (2008) Biopieces: a bioinformatics toolset and framework. In: 19th International Conference on Genome InformaticsGoogle Scholar
  23. 23.
    Wang Q, Garrity GM, Tiedje JM, Cole JR (2007) Naïve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 73(16):5261–5267. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Tange O (2011) GNU parallel - the command-line power tool. USENIX Mag 36(1):42–47Google Scholar
  25. 25.
    Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215(3):403–410. CrossRefGoogle Scholar
  26. 26.
    Morgulis A, Coulouris G, Raytselis Y, Madden TL, Agarwala R, Schäffer AA (2008) Database indexing for production MegaBLAST searches. Bioinformatics 24(16):1757–1764. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    R Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna URL http://www.R-projectorg/. Accessed July 2017
  28. 28.
    Lozupone C, Knight R (2005) UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 71(12):8228–8235. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lagkouvardos I, Fischer S, Kumar N, Clavel T (2017) Rhea: a transparent and modular R pipeline for microbial profiling based on 16S rRNA gene amplicons. PeerJ 5:e2836. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    D’Argenio V, Salvatore F (2015) The role of the gut microbiome in the healthy adult status. Clin Chim Acta 451:97–102. CrossRefPubMedGoogle Scholar
  31. 31.
    Bioinformatics and Evolutionary Genomics group GU Calculate and draw custom Venn diagrams. June 2018
  32. 32.
    Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484. CrossRefPubMedGoogle Scholar
  33. 33.
    Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3(4):213–223. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102(31):11070–11075. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023 CrossRefGoogle Scholar
  36. 36.
    Xiao L, Feng Q, Liang S, Sonne SB, Xia Z, Qiu X, Li X, Long H, Zhang J, Zhang D, Liu C, Fang Z, Chou J, Glanville J, Hao Q, Kotowska D, Colding C, Licht TR, Wu D, Yu J, Sung JJY, Liang Q, Li J, Jia H, Lan Z, Tremaroli V, Dworzynski P, Nielsen HB, Backhed F, Dore J, Le Chatelier E, Ehrlich SD, Lin JC, Arumugam M, Wang J, Madsen L, Kristiansen K (2015) A catalog of the mouse gut metagenome. Nat Biotechnol 33(10):1103–1108. Scholar
  37. 37.
    Daft JG, Ptacek T, Kumar R, Morrow C, Lorenz RG (2015) Cross-fostering immediately after birth induces a permanent microbiota shift that is shaped by the nursing mother. Microbiome 3:17. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee Ying S, De Vadder F, Arora T, Hallen A, Martens E, Björck I, Bäckhed F (2015) Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab 22(6):971–982. CrossRefPubMedGoogle Scholar
  39. 39.
    Kanai T, Mikami Y, Hayashi A (2015) A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease. J Gastroenterol 50(9):928–939. CrossRefPubMedGoogle Scholar
  40. 40.
    Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13(9):R79–R79. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Goodrich JK, Davenport ER, Beaumont M, Jackson MA, Knight R, Ober C, Spector TD, Bell JT, Clark AG, Ley RE (2016) Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19(5):731–743. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Leamy LJ, Kelly SA, Nietfeldt J, Legge RM, Ma F, Hua K, Sinha R, Peterson DA, Walter J, Benson AK, Pomp D (2014) Host genetics and diet, but not immunoglobulin A expression, converge to shape compositional features of the gut microbiome in an advanced intercross population of mice. Genome Biol 15(12):552. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Callahan BJ, McMurdie PJ, Holmes SP (2017) Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. ISME J 11:2639–2643. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Martín R, Langa S, Reviriego C, Jimínez E, Marín ML, Xaus J, Fernández L, Rodríguez JM (2003) Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr 143(6):754–758. CrossRefPubMedGoogle Scholar
  45. 45.
    Heikkilä MP, Saris PE (2003) Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. J Appl Microbiol 95(3):471–478. CrossRefPubMedGoogle Scholar
  46. 46.
    Marcobal A, Barboza M, Froehlich JW, Block DE, German JB, Lebrilla CB, Mills DA (2010) Consumption of human milk oligosaccharides by gut-related microbes. J Agric Food Chem 58(9):5334–5340. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Hildebrandt MA, Hoffman C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen Y-Y, Knight R, Ahima RS, Bushman F, Wu GD (2009) High fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137(5):1716–1724.e1711-1712. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Moon C, Baldridge MT, Wallace MA, Burnham DC-A, Virgin HW, Stappenbeck TS (2015) Vertically transmitted fecal IgA levels distinguish extra-chromosomal phenotypic variation. Nature 521(7550):90–93. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489:220–230. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Nicole Simone Treichel
    • 1
  • Zala Prevoršek
    • 2
  • Vesna Mrak
    • 2
  • Matea Kostrić
    • 1
  • Gisle Vestergaard
    • 1
    • 3
  • Bärbel Foesel
    • 1
    Email author
  • Stefan Pfeiffer
    • 1
    • 4
  • Blaž Stres
    • 2
  • Anne Schöler
    • 1
    • 5
  • Michael Schloter
    • 1
    • 4
  1. 1.Research Unit Comparative Microbiome AnalysisHelmholtz Zentrum MünchenNeuherbergGermany
  2. 2.Department of Animal ScienceUniversity of LjubljanaLjubljanaSlovenia
  3. 3.Molecular Microbial Ecology GroupUniversity of CopenhagenCopenhagenDenmark
  4. 4.ZIEL - Institute for Food & HealthTechnical University of MunichFreisingGermany
  5. 5.DKFZ German Cancer Research CenterBerlinGermany

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