Skip to main content
Log in

Mucin Cross-Feeding of Infant Bifidobacteria and Eubacterium hallii

  • Physiology and Biotechnology
  • Published:
Microbial Ecology Aims and scope Submit manuscript

Abstract

Mucus production is initiated before birth and provides mucin glycans to the infant gut microbiota. Bifidobacteria are the major bacterial group in the feces of vaginally delivered and breast milk-fed infants. Among the bifidobacteria, only Bifidobacterium bifidum is able to degrade mucin and to release monosaccharides which can be used by other gut microbes colonizing the infant gut. Eubacterium hallii is an early occurring commensal that produces butyrate and propionate from fermentation metabolites but that cannot degrade complex oligo- and polysaccharides. We aimed to demonstrate that mucin cross-feeding initiated by B. bifidum enables growth and metabolite formation of E. hallii leading to short-chain fatty acid (SCFA) formation. Growth and metabolite formation of co-cultures of B. bifidum, of Bifidobacterium breve or Bifidobacterium infantis, which use mucin-derived hexoses and fucose, and of E. hallii were determined. Growth of E. hallii in the presence of lactose and mucin monosaccharides was tested. In co-culture fermentations, the presence of B. bifidum enabled growth of the other strains. B. bifidum/B. infantis co-cultures yielded acetate, formate, and lactate while co-cultures of B. bifidum and E. hallii formed acetate, formate, and butyrate. In three-strain co-cultures, B. bifidum, E. hallii, and B. breve or B. infantis produced up to 16 mM acetate, 5 mM formate, and 4 mM butyrate. The formation of propionate (approximately 1 mM) indicated cross-feeding on fucose. Lactose, galactose, and GlcNAc were identified as substrates of E. hallii. This study shows that trophic interactions of bifidobacteria and E. hallii lead to the formation of acetate, butyrate, propionate, and formate, potentially contributing to intestinal SCFA formation with potential benefits for the host and for microbial colonization of the infant gut. The ratios of SCFA formed differed depending on the microbial species involved in mucin cross-feeding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brockhausen I, Schachter H, Stanely P (2009) O-GalNAc glycans. In: Varki A, Cummings RD, Esko JD, et al. (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor,

    Google Scholar 

  2. Pelaseyed T, Bergström JH, Gustafsson JK, et al. (2014) The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system Immunol Rev 260:8–20

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Tailford LE, Crost EH, Kavanaugh D, Juge N (2015) Mucin glycan foraging in the human gut microbiome Front Genet 6:81

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Koropatkin NM, Cameron EA, Martens EC (2014) How glycan metabolism shapes the human gut microbiota Nat Rev Microbiol 10:323–335

    Article  CAS  Google Scholar 

  5. Avershina E, Storrø O, Øien T, et al. (2013) Bifidobacterial succession and correlation networks in a large unselected cohort of mothers and their children Appl Environ Microbiol 79:494–507

    Article  CAS  Google Scholar 

  6. Sun Z, Zhang W, Guo C, et al. (2015) Comparative genomic analysis of 45 type strains of the genus Bifidobacterium: a snapshot of its genetic diversity and evolution PLoS One 10:e0117912

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Bottacini F, Ventura M, Van Sinderen D, Motherway MOC (2014) Diversity, ecology and intestinal function of bifidobacteria Microb Cell Factories 13:1024

    Article  Google Scholar 

  8. Sela DA, Chapman J, Adeuya A, et al. (2008) The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome Proc Natl Acad Sci U S A. 105:18964–18969

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rockova S, Rada V, Nevoral J, Marsik P, Vlkova E, Bunesova V (2012) Inter-species differences in the growth of bifidobacteria cultured on human milk oligosaccharides Folia Microbiol 57:321–324

    Article  CAS  Google Scholar 

  10. LoCascio RG, Desai P, Sela DA, Weimer B, Mills DA (2010) Broad conservation of milk utilization genes in Bifidobacterium longum subsp. infantis as revealed by comparative genomic hybridization Appl Environ Microbiol 76:7373–7381

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Turroni F, Duranti S, Bottacini F, Guglielmetti S, Van Sinderen D, Ventura M (2014) Bifidobacterium bifidum as an example of a specialized human gut commensal Front Microbiol 5:437

    Article  PubMed  PubMed Central  Google Scholar 

  12. Milani C, Luigli GA, Duranti S, et al. (2015) Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut Sci Rep 5:15782

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Duranti S, Milani C, Lugli GA, et al. (2015) Insights from genomes of representatives of the human gut commensal Bifidobacterium bifidum Environ Microbiol 17:2515–2531

    Article  PubMed  CAS  Google Scholar 

  14. Ruas-Madiedo P, Gueimonde M, Fernández-García M, de los Reyes-Gavilán CG, Margolles A (2008) Mucin degradation by Bifidobacterium strains isolated from the human intestinal microbiota Appl Environ Microbiol 74:1936–1940

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Garrido D, Ruiz-Moyano S, Lemy DG, Sela DA, German JB, Mills DA (2015) Comparative genomics reveals key differences in response to milk oligosaccharides of infant gut-associated bifidobacteria Sci Rep 4:5

    Google Scholar 

  16. Egan M, Motherway MOC, Kilcoyne M, et al. (2014) Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium BMC Microbiol 14:282

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. de Vries W, Stouthamer AH (1967) Pathway of glucose fermentation in relation to the taxonomy of bifidobacteria J Bacteriol 93:574–576

    PubMed  PubMed Central  Google Scholar 

  18. Palframan RJ, Gibson GR, Rastall RA (2003) Carbohydrate preferences of Bifidobacterium species isolated from the human gut Curr Issues Intes Microbiol 4:71–75

    CAS  Google Scholar 

  19. Schwab C, Ruscheweyh HJ, Bunesova V, Pham VT, Beerenwinkel N, Lacroix C (2017) Trophic interactions of infant bifidobacteria and Eubacterium hallii during L-fucose and fucosyllactose degradation Front Microbiol 8:95

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bunesova V, Lacroix C, Schwab C (2016) Fucosyllactose and L-fucose utilization of infant Bifidobacterium longum and Bifidobacterium kashiwanohense BMC Microbiol 16:248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Reichardt N, Duncan SH, Young P, et al. (2014) Phylogenetic distribution of three pathways for propionate production within the human gut microbiota ISME J 8:1323–1335

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Engels C, Ruscheweyh H-J, Beerenwinkel N, Lacroix C, Schwab C (2016) The common gut microbe Eubacterium hallii also contributes to intestinal propionate formation Front Microbiol 7:713

    Article  PubMed  PubMed Central  Google Scholar 

  23. Scott KP, Martin JC, Duncan SH, Flint HJ (2013) Prebiotic simulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro FEMS Microbiol Ecol 87:30–40

    Article  PubMed  CAS  Google Scholar 

  24. Wang JMW, de Souza R, Kendall CWC, Emam A, Jenkins DJA (2006) Colonic health: fermentation and short chain fatty acids J Clin Gastroenterol 40:235–243

    Article  CAS  Google Scholar 

  25. Vazquez-Gutierrez P, Lacroix C, Jaeggi T, Zeder C, Zimmerman MB, Chassard C (2015) Bifidobacteria strains isolated from stools of iron deficient infants can efficiently sequester iron BMC Microbiol 15:3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Duncan SH, Hold GL, Barcenilla A, Stewart CS, Flint HJ (2002) Lactate-utilizing bacteria, isolated from human feces that produce butyrate as a major fermentation product Appl Environ Microbiol 70:5810–5817

    Article  CAS  Google Scholar 

  27. Ramirez-Farias C, Slezak K, Fuller Z, Duncan A, Holtrop G, Louis P (2009) Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov Int J Syst Evol Microbiol 52:2141–2146

    Google Scholar 

  28. Matsuki T, Watanabe K, Fujimoto J, et al. (2004) Quantitative PCR with 16S rRNA-gene-targeted species-specific primers for analysis of human intestinal bifidobacteria Appl Environ Microbiol 70:167–173

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Liu S, Ren F, Zhao L, et al. (2015) Starch and starch hydrolysates are favorable carbon sources for bifidobacteria in the human gut BMC Microbiol 15:54

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Vanderhaeghen S, Lacroix C, Schwab C (2015) Methanogen communities in stools of humans of different age and health status and co-occurrence with bacteria FEMS Microbiol Lett 362:fnv092

    Article  PubMed  Google Scholar 

  31. Stoddard SF, Smith BJ, Hein R, Roller BRK, Schmidt TM (2015) rrnDB: improved tools for interpreting rRNA gene abundance in bacteria and archaea and a new foundation for future development Nucleic Acids Res 43:D593–D598

    Article  PubMed  CAS  Google Scholar 

  32. Větrovský T, Baldrian P (2013) The variability of the 16S rRNA gene in bacterial genomes and its consequences for bacterial community analyses PLoS One 8:e57923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Aziz RK, Bartels D, Best AA, et al. (2008) The RAST Server: rapid annotations using subsystems technology BMC Genomics 9:75

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Holden HM, Rayment I, Thoden JB (2003) Structure and function of enzymes of the Leloir pathway for galactose metabolism J Biol Chem 278:43885–43888

    Article  PubMed  CAS  Google Scholar 

  35. Vimr ER, Kalivoda KA, Deszo EL, Steenbergen SM (2004) Diversity of microbial sialic acid metabolism Microbiol Mol Biol Rev 68:132–153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Turroni F, Bottacini F, Foroni E, et al. (2010) Genome analysis of Bifidobacterium bifidum PRL2010 reveals metabolic pathways for host-derived glycan foraging Proc Natl Acad Sci U S A 107:19514–19519

    Article  PubMed  PubMed Central  Google Scholar 

  37. Turroni F, Milani C, van Sinderen D, Ventura M (2011) Genetic strategies for mucin metabolism in Bifidobacterium bifidum PRL2010: an example of possible human-microbe co-evolution Gut Microbes 2:183–189

    Article  PubMed  Google Scholar 

  38. Pham VT, Lacroix C, Braegger CP, Chassard C (2016) Early colonization of functional groups of microbes in the infant gut Environ Microbiol 18:2246–2258

    Article  PubMed  CAS  Google Scholar 

  39. Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ (2002) Acetate utilization and butyryl coenzyme A (CoA):acetate CoA transferase in butyrate-producing bacteria from the human large intestine Appl Environ Microbiol 68:5186–5190

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Naseem S, Konopka JB (2015) N-acetylglucosamine regulates virulence properties in microbial pathogens PLoS Pathog 11:e1004947

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Magnusdottir S, Heinken A, Kutt L, et al. (2017) Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota Nat Biotechnol 35:81–89

    Article  PubMed  CAS  Google Scholar 

  42. Schwab C, Gänzle MG (2011) Lactic acid bacteria fermentation of human milk oligosaccharide components, human milk oligosaccharides and galactooligosaccharides FEMS Microbiol Lett 315:141–148

    Article  PubMed  CAS  Google Scholar 

  43. Belenguer A, Duncan SH, Graham Calder A, et al. (2006) Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut Appl Environ Microbiol 72:3593–3599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Moens F, Verce M, de Vuyst L (2017) Lactate- and acetate-based cross-feeding interactions between selected strains of lactobacilli, bifidobacteria and colon bacteria in the presence of inulin-type fructans Int J Food Microbiol 241:225–236

    Article  PubMed  CAS  Google Scholar 

  45. Louis P, Flint HJ (2016) Formation of propionate and butyrate by the human colonic microbiota Environ Microbiol 19:29–41

    Article  PubMed  CAS  Google Scholar 

  46. Midtvedt AC, Carlstedt-Duke B, Midtvedt T (1994) Establishment of a mucin-degrading intestinal microflora during the first two years of human life J Ped Gastroenterol Nutr 18:321–326

    Article  CAS  Google Scholar 

  47. Fuchs G (1986) CO2 fixation in acetogenic bacteria: variations on a theme FEMS Microbiol Rev 39:181–213

    Article  CAS  Google Scholar 

  48. Liu Y, Whitman WB (2008) Metabolic, phylogenetic and ecological diversity of methanogenic archaea Ann N Y Acad Sci 1125:171–189

    Article  PubMed  CAS  Google Scholar 

  49. Yatsunenko T, Rey FE, Manary MJ, et al. (2012) Human gut microbiome viewed across age and geography Nature 486:222–228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Rey FE, Faith JJ, Bain J, et al. (2010) Dissecting the in vivo metabolic potential of two human gut acetogens J Biol Chem 285:22082–22090

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

Vera Bunesova was supported by SCIEX grant 13.151. The authors thank Alfonso Die for technical assistance and Glycom A/S, Denmark, for supplying NANA.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clarissa Schwab.

Electronic Supplementary Material

ESM 1

(DOCX 59.6 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bunesova, V., Lacroix, C. & Schwab, C. Mucin Cross-Feeding of Infant Bifidobacteria and Eubacterium hallii . Microb Ecol 75, 228–238 (2018). https://doi.org/10.1007/s00248-017-1037-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00248-017-1037-4

Keywords

Navigation