Fucosyllactoses (2'- or 3'-FL) account for up to 20% of human milk oligosaccharides (HMOs). Infant bifidobacteria, such as Bifidobacterium longum subsp. infantis, utilize the lactose moiety to form lactate and acetate, and metabolize L-fucose to 1,2-propanediol (1,2-PD). Eubacterium hallii is a common member of the adult gut microbiota that can produce butyrate from lactate and acetate, and convert 1,2-PD to propionate. Recently, a Swiss cohort study identified E. hallii as one of the first butyrate producers in the infant gut. However, the global prevalence of E. hallii and its role in utilization of HMO degradation intermediates remains unexplored. Fecal 16S rRNA gene libraries (n = 857) of humans of all age groups from Venezuela, Malawi, Switzerland, and the USA were screened for the occurrence of E. hallii. Single and co-culture experiments of B. longum subsp. infantis and E. hallii were conducted in modified YCFA containing acetate and glucose, L-fucose, or FL. Bifidobacterium spp. (n = 56) of different origin were screened for the ability to metabolize L-fucose. Relative abundance of E. hallii was low (10-5-10-3%) during the first months but increased and reached adult levels (0.01-10%) at 5-10 years of age in all four populations. In single culture, B. longum subsp. infantis grew in the presence of all three carbohydrates while E. hallii was metabolically active only with glucose. In co-culture E. hallii also grew with L-fucose or FL. In co-cultures grown with glucose, acetate, and glucose were consumed and nearly equimolar proportions of formate and butyrate were formed. B. longum subsp. infantis used L-fucose and produced 1,2-PD, acetate and formate in a ratio of 1:1:1, while 1,2-PD was used by E. hallii to form propionate. E. hallii consumed acetate, lactate and 1,2-PD released by B. longum subsp. infantis from FL, and produced butyrate, propionate, and formate. Beside B. longum subsp. infantis, Bifidobacterium breve, and a strain of B. longum subsp. suis were able to utilize L-fucose. This study identified a trophic interaction of infant bifidobacteria and E. hallii during L-fucose degradation, and pointed at E. hallii as a metabolically versatile species that occurs in infants and utilizes intermediates of bifidobacterial HMO fermentation.

Department of Biosystems Science and Engineering ETH ZurichBasel Switzerland; Scientific IT Services ETH ZurichBasel Switzerland; Swiss Institute of BioinformaticsBasel Switzerland

Department of Biosystems Science and Engineering ETH ZurichBasel Switzerland; Swiss Institute of BioinformaticsBasel Switzerland

Laboratory of Food Biotechnology Department of Health Sciences and Technology ETH Zurich Zurich Switzerland

Laboratory of Food Biotechnology Department of Health Sciences and Technology ETH ZurichZurich Switzerland; Department of Microbiology Nutrition and Dietetics Czech University of Life Sciences PraguePrague Czechia

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Avershina E., Storrø O., Øien T., Johnsen R., Wilson R., Egeland T., et al. . (2013). Bifidobacterial succession and correlation networks in a large unselected cohort of mothers and their children. Appl. Environ. Microbiol. 79, 494–407. 10.1128/aem.02359-12 PubMed DOI PMC

Becker D. J., Lowe J. B. (2003). Fucose: biosynthesis and biological function in mammals. Glycobiology 13, 41–53. 10.1093/glycob/cwg054 PubMed DOI

Belenguer A., Duncan S. H., Calder A. G., Holtrop G., Louis P., Lobley G. E., 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. 10.1128/AEM.72.5.3593-3599.2006 PubMed DOI PMC

Buchfink B., Xie C., Huson D. H. (2015). Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60. 10.1038/nmeth.3176 PubMed DOI

Bunesova V., Lacroix C., Schwab C. (2016). Fucosyllactose and L-fucose utilization of infant Bifidobacterium longum and Bifidobacterium kashiwanohense. BMC Microbiol. 16:248. 10.1186/s12866-016-0867-4 PubMed DOI PMC

de Leoz M. L., Gaerlan S. C., Strum J. S., Dimapasoc L. M., Mirmiran M., Tancredi D. J., et al. . (2012). Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm. J. Proteome Res. 11, 4662–4672. 10.1021/pr3004979 PubMed DOI PMC

de Vries W., Stouthamer A. H. (1967). Pathway of glucose fermentation in relation to the taxonomy of bifidobacteria. J. Bacteriol. 93, 574–576. PubMed PMC

de Vries W., Stouthamer A. H. (1968). Fermentation of glucose, lactose, galactose, mannitol, and xylose by bifidobacteria. J. Bacteriol. 96, 472–478. PubMed PMC

Duncan S. H., Louis P., Flint H. J. (2004). Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl. Environ. Microbiol. 70, 5810–5817. 10.1128/AEM.70.10.5810-5817.2004 PubMed DOI PMC

Egan M., O'Connell Motherway M., Kilcoyne M., Kane M., Joshi L., Ventura 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. 10.1186/s12866-014-0282-7 PubMed DOI PMC

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. 10.3389/fmicb.2016.00713 PubMed DOI PMC

Fierer N., Jackson J. A., Vilgalys R., Jackson R. B. (2005). Assessment of soil microbial community structure by use of taxon-specific quantitative PCR assays. Appl. Environ. Microbiol. 71, 4117–4120. 10.1128/AEM.71.7.4117-4120.2005 PubMed DOI PMC

Garrido D., Ruiz-Moyano S., Kirmiz N., Davis J. C. C., Totten S., Lemay D. G., et al. . (2016). A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596. Sci. Rep. 6:35045. 10.1038/srep35045 PubMed DOI PMC

Garrido D., Ruiz-Moyano S., Lemay D. G., Sela D. A., German J. B., Mills D. A. (2015). Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci. Rep. 5:13517. 10.1038/srep13517 PubMed DOI PMC

González R., Blancas A., Santillana R., Azaola A., Wacher C. (2004). Growth and final product formation by Bifidobacterium infantis in aerated fermentations. Appl. Microbiol. Biotechnol. 65, 606–610. 10.1007/s00253-004-1603-9 PubMed DOI

Herbig A., Maixner F., Bos K. I., Zink A., Krause J., Huson D. H. (2016). MALT: fast alignment and analysis of metagenomic DNA sequence data applied to the Tyrolean Iceman. bioRxiv 050559 10.1101/050559 DOI

Jost T., Lacroix C., Braegger C. P., Rochat F., Chassard C. (2014). Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environ. Microbiol. 16, 2891–2904. 10.1111/1462-2920.12238 PubMed DOI

Kelly R. J., Rouquier S., Giorgi D., Lennon G. G., Lowe J. B. (1995). Sequence and expression of a candidate for the human secretor blood group α(1, 2)fucosyltransferase gene (FUT2). J. Biol. Chem. 270, 4640–4649. 10.1074/jbc.270.9.4640 PubMed DOI

Kunz C., Rudloff S., Baier W., Klein N., Strobel S. (2000). Oligosaccharides in human milk. Structural, functional, and metabolic aspects. Annu. Rev. Nutr. 20, 699–722. 10.1146/annurev.nutr.20.1.699 PubMed DOI

Lewis Z. T., Totten S. M., Smilowitz J. T., Popovic M., Parker E., Lemay D. G., et al. . (2015). Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breasfed infants. Microbiome 3, 13. 10.1186/s40168-015-0071-z PubMed DOI PMC

Liu Y., Koda Y., Soejima M., Pang H., Schlaphoff T., du Toit E. D., et al. . (1998). Extensive polymorphism of the FUT2 gene in an African (Xhosa) population of South Africa. Hum. Genet. 103, 204–210. 10.1007/s004390050808 PubMed DOI

LoCascio R. G., Desai P., Sela D. A., Weimer B., Mills D. A. (2010). Broad conservation of milk utilization genes in Bifidobacterium longum subsp. infantis as revealed by comparative genomic hybridization. Appl. Environ. Microbiol. 76, 7373–7381. 10.1128/AEM.00675-10 PubMed DOI PMC

Macfarlane G. T., Gibson G. R. (1995). Microbiological aspects of short chain fatty acid production in the large bowel, in Physiological and Clinical Aspects of Short Chain Fatty Acid Metabolism, eds Cummings J. H., Rombeau J. L., Sakata T. (Cambridge: Cambridge University Press; ), 87–105.

Matsuki T., Yahagi K., Mori H., Matsumoto H., Hara T., Tajima S., et al. . (2016). A key genetic factor for fucosyllactose utilization affects infant gut microbiota development. Nat. Commun. 7:11939. 10.1038/ncomms11939 PubMed DOI PMC

Morrow A. L., Ruiz-Palacios G. M., Jiang X., Newburg D. S. (2005). Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea. J. Nutr. 135, 1304–1307. 10.1146/annurev.nutr.25.050304.092553 PubMed DOI

Muraoka W. T., Zhang Q. (2011). Phenotypic and genotypic evidence for L-fucose utilization by Campylobacter jejuni. J. Bacteriol. 193, 1065–1075. 10.1128/JB.01252-10 PubMed DOI PMC

Ng K. M., Ferreyra J. A., Higginbottom S. K., Lynch J. B., Kashyap P. C., Gopinath S., et al. . (2013). Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502, 96–99. 10.1038/nature12503 PubMed DOI PMC

Niñonuevo M. R., Perkins P. D., Francis J., Lamotte L. M., LoCascio R. G., Freeman S. L, et al. . (2008). Daily variations in oligosaccharides of human milk determined by microfluidic chips and mass spectrometry. J. Agric. Food Chem. 56, 618–626. 10.1021/jf071972u PubMed DOI

Pacheco A. R., Curtis M. M., Ritchie J. M., Munera D., Waldor M. K., Moreira C. G., et al. . (2012). Fucose sensing regulates bacterial intestinal colonization. Nature 492, 113–117. 10.1038/nature11623 PubMed DOI PMC

Palframan R. J., Gibson G. R., Rastall R. A. (2003). Carbohydrate preferences of Bifidobacterium species isolated from the human gut. Curr. Issues Intest. Microbiol. 4, 71–75. PubMed

Pham V. T., Lacroix C., Braegger C. P., Chassard C. (2016). Early colonization of functional groups of microbes in the infant gut. Environ. Microbiol. 18, 2246–2258. 10.1111/1462-2920.13316 PubMed DOI

Pickard J. M., Maurice C. F., Kinnebrew M. A., Abt M. C., Schenten D., Golovkina T. V., et al. . (2014). Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature 514, 638–641 10.1038/nature13823 PubMed DOI PMC

Plöger S., Stumpff F., Penner G. B., Schulzke J. D., Gabel G., Martens H., et al. . (2012). Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann. N.Y. Acad. Sci. 1258, 52–59. 10.1111/j.1749-6632.2012.06553.x PubMed DOI

Pruitt K. D., Tatusova T., Maglott D. R. (2007). NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 35, D61–D65. 10.1093/nar/gkl842 PubMed DOI PMC

Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P., et al. . (2013). The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 41, D590–D596. 10.1093/nar/gks1219 PubMed DOI PMC

Ramirez-Farias C., Slezak K., Fuller Z., Duncan A., Holtrop G., Louis P. (2009). Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br. J. Nutr. 101, 541–550. 10.1017/S0007114508019880 PubMed DOI

Reichardt N., Duncan S. H., Young P., Belenguer A., McWilliam Leitch C., Scott K. P., et al. . (2014). Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 8, 1323–1335. 10.1038/ismej.2014.14 PubMed DOI PMC

Rinttilä T., Kassinen A., Malinen E., Krogius L., Palva A. (2004). Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J. Appl. Microbiol. 97, 1166–1177. 10.1111/j.1365-2672.2004.02409.x PubMed DOI

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. 10.1007/s12223-012-0134-5 PubMed DOI

Sela D. A., Garrido D., Lerno L., Wu S., Eom H.J., Joachimiak A., et al. . (2012). Bifidobacterium longum subsp. infantis ATCC 15697 α-fucosidases are active on fucosylated human milk oligosaccharides. Appl. Environ. Microbiol. 78, 795–803. 10.1128/AEM.06762-11 PubMed DOI PMC

Stahl M., Friis L. M., Nothaft H., Liu X., Li J., Szymanski C. M. (2011). L-fucose utilization provides Campylobacter jejuni with a competitive advantage. Proc. Natl. Acad. Sci. U.S.A. 108, 7194–7199. 10.1073/pnas.1014125108 PubMed DOI PMC

Staib L., Fuchs T. M. (2014). From food to cell: nutrient exploitation strategies of enteropathogens. Microbiol. 160, 1020–1039. 10.1099/mic.0.078105-0 PubMed DOI

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. 10.3389/fmicb.2014.00437 PubMed DOI PMC

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. 10.1093/femsle/fnv092 PubMed DOI

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. 10.1371/journal.pone.0057923 PubMed DOI PMC

Wong J. M., deSouza R., Kendall C. W., Emam A., Jenkins D. J. (2006). Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol. 40, 235–243. 10.1097/00004836-200603000-00015 PubMed DOI

Yatsunenko T., Rey F. E., Manary M. J., Trehan I., Dominguez-Bello M. G., Contreras M., et al. . (2012). Human gut microbiome viewed across age and geography. Nature 486, 222–228. 10.1038/nature11053 PubMed DOI PMC

Breastfeeding and the major fermentation metabolite lactate determine occurrence of Peptostreptococcaceae in infant feces

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