No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Bifidobacteria and Their Health-Promoting Effects

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Claudio Hidalgo-Cantabrana1, Susana Delgado2, Lorena Ruiz3, Patricia Ruas-Madiedo4, Borja Sánchez5, Abelardo Margolles6
  • Editors: Robert Allen Britton7, Patrice D. Cani8
    Affiliations: 1: Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares s/n 33300, Villaviciosa, Asturias, Spain; 2: Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares s/n 33300, Villaviciosa, Asturias, Spain; 3: Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares s/n 33300, Villaviciosa, Asturias, Spain; 4: Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares s/n 33300, Villaviciosa, Asturias, Spain; 5: Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares s/n 33300, Villaviciosa, Asturias, Spain; 6: Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares s/n 33300, Villaviciosa, Asturias, Spain; 7: Baylor College of Medicine, Houston, TX; 8: Université catholique de Louvain, Brussels, Belgium
  • Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0010-2016
  • Received 02 December 2016 Accepted 25 January 2017 Published 23 June 2017
  • Abelardo Margolles, amargolles@ipla.csic.es
image of Bifidobacteria and Their Health-Promoting Effects
    Preview this microbiology spectrum article:
    Zoom in

    Bifidobacteria and Their Health-Promoting Effects, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/5/3/BAD-0010-2016-1.gif /docserver/preview/fulltext/microbiolspec/5/3/BAD-0010-2016-2.gif
  • Abstract:

    Bifidobacteria are members of the intestinal microbiota of mammals and other animals, and some strains are able to exert health-promoting effects. The genus belongs to the phylum. , , and constitute the most abundant phyla in the human intestinal microbiota, and being predominant in adults, and in breast-fed infants, where bifidobacteria can reach levels higher than 90% of the total bacterial population. They are among the first microbial colonizers of the intestines of newborns, and play key roles in the development of their physiology, including maturation of the immune system and use of dietary components. Indeed, some nutrients, such as human milk oligosaccharides, are important drivers of bifidobacterial development. Some strains are considered probiotic microorganisms because of their beneficial effects, and they have been included as bioactive ingredients in functional foods, mainly dairy products, as well as in food supplements and pharma products, alone, or together with, other microbes or microbial substrates. Well-documented scientific evidence of their activities is currently available for bifidobacteria-containing preparations in some intestinal and extraintestinal pathologies. In this review, we focus on the role of bifidobacteria as members of the human intestinal microbiota and their use as probiotics in the prevention and treatment of disease.

  • Citation: Hidalgo-Cantabrana C, Delgado S, Ruiz L, Ruas-Madiedo P, Sánchez B, Margolles A. 2017. Bifidobacteria and Their Health-Promoting Effects. Microbiol Spectrum 5(3):BAD-0010-2016. doi:10.1128/microbiolspec.BAD-0010-2016.

Key Concept Ranking

Confocal Laser Scanning Microscopy


1. González-Rodríguez I, Gaspar P, Sánchez B, Gueimonde M, Margolles A, Neves AR. 2013. Catabolism of glucose and lactose in Bifidobacterium animalis subsp. lactis, studied by 13C Nuclear Magnetic Resonance. Appl Environ Microbiol 79:7628–7638. http://dx.doi.org/10.1128/AEM.02529-13
2. Schell MA, Karmirantzou M, Snel B, Vilanova D, Berger B, Pessi G, Zwahlen MC, Desiere F, Bork P, Delley M, Pridmore RD, Arigoni F. 2002. The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc Natl Acad Sci USA 99:14422–14427. http://dx.doi.org/10.1073/pnas.212527599
3. Lugli GA, Milani C, Turroni F, Duranti S, Ferrario C, Viappiani A, Mancabelli L, Mangifesta M, Taminiau B, Delcenserie V, van Sinderen D, Ventura M. 2014. Investigation of the evolutionary development of the genus Bifidobacterium by comparative genomics. Appl Environ Microbiol 80:6383–6394. http://dx.doi.org/10.1128/AEM.02004-14
4. Milani C, Lugli GA, Duranti S, Turroni F, Bottacini F, Mangifesta M, Sanchez B, Viappiani A, Mancabelli L, Taminiau B, Delcenserie V, Barrangou R, Margolles A, van Sinderen D, Ventura M. 2014. Genomic encyclopedia of type strains of the genus Bifidobacterium. Appl Environ Microbiol 80:6290–6302. http://dx.doi.org/10.1128/AEM.02308-14
5. Delgado S, Suárez A, Mayo B. 2006. Bifidobacterial diversity determined by culturing and by 16S rDNA sequence analysis in feces and mucosa from ten healthy Spanish adults. Dig Dis Sci 51:1878–1885. http://dx.doi.org/10.1007/s10620-006-9293-z
6. Turroni F, Foroni E, Pizzetti P, Giubellini V, Ribbera A, Merusi P, Cagnasso P, Bizzarri B, de’Angelis GL, Shanahan F, van Sinderen D, Ventura M. 2009. Exploring the diversity of the bifidobacterial population in the human intestinal tract. Appl Environ Microbiol 75:1534–1545. http://dx.doi.org/10.1128/AEM.02216-08
7. Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I, Dewhirst FE, Leys EJ, Paster BJ. 2008. Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol 46:1407–1417. http://dx.doi.org/10.1128/JCM.01410-07
8. Ventura M, Turroni F, Zomer A, Foroni E, Giubellini V, Bottacini F, Canchaya C, Claesson MJ, He F, Mantzourani M, Mulas L, Ferrarini A, Gao B, Delledonne M, Henrissat B, Coutinho P, Oggioni M, Gupta RS, Zhang Z, Beighton D, Fitzgerald GF, O’Toole PW, van Sinderen D. 2009. The Bifidobacterium dentium Bd1 genome sequence reflects its genetic adaptation to the human oral cavity. PLoS Genet 5:e1000785. http://dx.doi.org/10.1371/journal.pgen.1000785
9. Turroni F, Marchesi JR, Foroni E, Gueimonde M, Shanahan F, Margolles A, van Sinderen D, Ventura M. 2009. Microbiomic analysis of the bifidobacterial population in the human distal gut. ISME J 3:745–751. http://dx.doi.org/10.1038/ismej.2009.19
10. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W. 2010. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One 5:e10667. (Erratum, 5: doi:10.1371/annotation/df45912f-d15c-44ab-8312-e7ec0607604d) http://dx.doi.org/10.1371/journal.pone.0010667
11. Drago L, Toscano M, Rodighiero V, De Vecchi E, Mogna G. 2012. Cultivable and pyrosequenced fecal microflora in centenarians and young subjects. J Clin Gastroenterol 46(Suppl):S81–S84. http://dx.doi.org/10.1097/MCG.0b013e3182693982
12. Woodmansey EJ, McMurdo ME, Macfarlane GT, Macfarlane S. 2004. Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects. Appl Environ Microbiol 70:6113–6122. http://dx.doi.org/10.1128/AEM.70.10.6113-6122.2004
13. Russell DA, Ross RP, Fitzgerald GF, Stanton C. 2011. Metabolic activities and probiotic potential of bifidobacteria. Int J Food Microbiol 149:88–105. http://dx.doi.org/10.1016/j.ijfoodmicro.2011.06.003
14. Nishijima S, Suda W, Oshima K, Kim SW, Hirose Y, Morita H, Hattori M. 2016. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res 23:125–133. http://dx.doi.org/10.1093/dnares/dsw002
15. Avershina E, Storrø O, Øien T, Johnsen R, Wilson R, Egeland T, Rudi K. 2013. Bifidobacterial succession and correlation networks in a large unselected cohort of mothers and their children. Appl Environ Microbiol 79:497–507. http://dx.doi.org/10.1128/AEM.02359-12
16. Tannock GW. 2010. Analysis of bifidobacterial populations in bowel ecology studies, p 1–15. In Mayo B, van Sinderen D (ed), Bifidobacteria: Genomics and Molecular Aspects. Caister Academic Press, Norfolk, England.
17. Fernández L, Langa S, Martín V, Jiménez E, Martín R, Rodríguez JM. 2013. The microbiota of human milk in healthy women. Cell Mol Biol Noisy-le-grand 59:31–42.
18. Martín R, Jiménez E, Heilig H, Fernández L, Marín ML, Zoetendal EG, Rodríguez JM. 2009. Isolation of bifidobacteria from breast milk and assessment of the bifidobacterial population by PCR-denaturing gradient gel electrophoresis and quantitative real-time PCR. Appl Environ Microbiol 75:965–969. http://dx.doi.org/10.1128/AEM.02063-08
19. Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, Corthier G, Furet JP. 2009. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9:123. http://dx.doi.org/10.1186/1471-2180-9-123
20. Roger LC, Costabile A, Holland DT, Hoyles L, McCartney AL. 2010. Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life. Microbiology 156:3329–3341. http://dx.doi.org/10.1099/mic.0.043224-0
21. Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. 2014. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu Rev Nutr 34:143–169. http://dx.doi.org/10.1146/annurev-nutr-071813-105721
22. Zivkovic AM, German JB, Lebrilla CB, Mills DA. 2011. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci USA 108(Suppl 1):4653–4658. http://dx.doi.org/10.1073/pnas.1000083107
23. Sela DA, Chapman J, Adeuya A, Kim JH, Chen F, Whitehead TR, Lapidus A, Rokhsar DS, Lebrilla CB, German JB, Price NP, Richardson PM, Mills DA. 2008. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc Natl Acad Sci USA 105:18964–18969. http://dx.doi.org/10.1073/pnas.0809584105
24. Wada J, Ando T, Kiyohara M, Ashida H, Kitaoka M, Yamaguchi M, Kumagai H, Katayama T, Yamamoto K. 2008. Bifidobacterium bifidum lacto-N-biosidase, a critical enzyme for the degradation of human milk oligosaccharides with a type 1 structure. Appl Environ Microbiol 74:3996–4004. http://dx.doi.org/10.1128/AEM.00149-08
25. Garrido D, Dallas DC, Mills DA. 2013. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications. Microbiology 159:649–664. http://dx.doi.org/10.1099/mic.0.064113-0
26. Garrido D, Ruiz-Moyano S, Lemay DG, Sela DA, German JB, Mills DA. 2015. Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci Rep 5:13517. http://dx.doi.org/10.1038/srep13517
27. Ruiz-Moyano S, Totten SM, Garrido DA, Smilowitz JT, German JB, Lebrilla CB, Mills DA. 2013. Variation in consumption of human milk oligosaccharides by infant gut-associated strains of Bifidobacterium breve. Appl Environ Microbiol 79:6040–6049. http://dx.doi.org/10.1128/AEM.01843-13 [PubMed]
28. Duranti S, Turroni F, Lugli GA, Milani C, Viappiani A, Mangifesta M, Gioiosa L, Palanza P, van Sinderen D, Ventura M. 2014. Genomic characterization and transcriptional studies of the starch-utilizing strain Bifidobacterium adolescentis 22L. Appl Environ Microbiol 80:6080–6090. http://dx.doi.org/10.1128/AEM.01993-14
29. Duranti S, Milani C, Lugli GA, Mancabelli L, Turroni F, Ferrario C, Mangifesta M, Viappiani A, Sánchez B, Margolles A, van Sinderen D, Ventura M. 2016. Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis. Sci Rep 6:23971. http://dx.doi.org/10.1038/srep23971
30. Ventura M, Canchaya C, Fitzgerald GF, Gupta RS, van Sinderen D. 2007. Genomics as a means to understand bacterial phylogeny and ecological adaptation: the case of bifidobacteria. Antonie van Leeuwenhoek 91:351–372. (Erratum, 92:265) http://dx.doi.org/10.1007/s10482-006-9122-6
31. Ventura M, Canchaya C, Tauch A, Chandra G, Fitzgerald GF, Chater KF, van Sinderen D. 2007. Genomics of Actinobacteria: tracing the evolutionary history of an ancient phylum. Microbiol Mol Biol Rev 71:495–548. http://dx.doi.org/10.1128/MMBR.00005-07
32. Ishikawa E, Matsuki T, Kubota H, Makino H, Sakai T, Oishi K, Kushiro A, Fujimoto J, Watanabe K, Watanuki M, Tanaka R. 2013. Ethnic diversity of gut microbiota: species characterization of Bacteroides fragilis group and genus Bifidobacterium in healthy Belgian adults, and comparison with data from Japanese subjects. J Biosci Bioeng 116:265–270. http://dx.doi.org/10.1016/j.jbiosc.2013.02.010
33. Turroni F, Peano C, Pass DA, Foroni E, Severgnini M, Claesson MJ, Kerr C, Hourihane J, Murray D, Fuligni F, Gueimonde M, Margolles A, De Bellis G, O’Toole PW, van Sinderen D, Marchesi JR, Ventura M. 2012. Diversity of bifidobacteria within the infant gut microbiota. PLoS One 7:e36957. http://dx.doi.org/10.1371/journal.pone.0036957
34. Ruiz L, Hevia A, Bernardo D, Margolles A, Sánchez B. 2014. Extracellular molecular effectors mediating probiotic attributes. FEMS Microbiol Lett 359:1–11. http://dx.doi.org/10.1111/1574-6968.12576
35. Gagnon M, Kheadr EE, Dabour N, Richard D, Fliss I. 2006. Effect of Bifidobacterium thermacidophilum probiotic feeding on enterohemorrhagic Escherichia coli O157:H7 infection in BALB/c mice. Int J Food Microbiol 111:26–33. http://dx.doi.org/10.1016/j.ijfoodmicro.2006.04.041
36. Henriksson A, Conway PL. 2001. Isolation of human faecal bifidobacteria which reduce signs of Salmonella infection when orogastrically dosed to mice. J Appl Microbiol 90:223–228. http://dx.doi.org/10.1046/j.1365-2672.2001.01238.x
37. Muñoz JA, Chenoll E, Casinos B, Bataller E, Ramón D, Genovés S, Montava R, Ribes JM, Buesa J, Fàbrega J, Rivero M. 2011. Novel probiotic Bifidobacterium longum subsp. infantis CECT 7210 strain active against rotavirus infections. Appl Environ Microbiol 77:8775–8783. http://dx.doi.org/10.1128/AEM.05548-11
38. Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, Tobe T, Clarke JM, Topping DL, Taylor TD, Itoh K, Kikuchi J, Morita H, Hattori M, Ohno H. 2011. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469:543–547.
39. Moroni O, Kheadr E, Boutin Y, Lacroix C, Fliss I. 2006. Inactivation of adhesion and invasion of food-borne Listeria monocytogenes by bacteriocin-producing Bifidobacterium strains of human origin. Appl Environ Microbiol 72:6894–6901.
40. Cotar AI, Chifiriuc MC, Dinu S, Pelinescu D, Banu O, Lazăr V. 2010. Quantitative real-time PCR study of the influence of probiotic culture soluble fraction on the expression of Pseudomonas aeruginosa quorum sensing genes. Roum Arch Microbiol Immunol 69:213–223. [PubMed]
41. Kim Y, Lee JW, Kang SG, Oh S, Griffiths MW. 2012. Bifidobacterium spp. influences the production of autoinducer-2 and biofilm formation by Escherichia coli O157:H7. Anaerobe 18:539–545. http://dx.doi.org/10.1016/j.anaerobe.2012.08.006
42. Fanning S, Hall LJ, Cronin M, Zomer A, MacSharry J, Goulding D, Motherway MO, Shanahan F, Nally K, Dougan G, van Sinderen D. 2012. Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection. Proc Natl Acad Sci USA 109:2108–2113. http://dx.doi.org/10.1073/pnas.1115621109
43. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, Angenent LT, Ley RE. 2011. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA 108(Suppl 1):4578–4585. http://dx.doi.org/10.1073/pnas.1000081107
44. Turroni F, Milani C, Duranti S, Mancabelli L, Mangifesta M, Viappiani A, Lugli GA, Ferrario C, Gioiosa L, Ferrarini A, Li J, Palanza P, Delledonne M, van Sinderen D, Ventura M. 2016. Deciphering bifidobacterial-mediated metabolic interactions and their impact on gut microbiota by a multi-omics approach. ISME J 10:1656–1668. http://dx.doi.org/10.1038/ismej.2015.236 [PubMed]
45. Arboleya S, Solís G, Fernández N, de los Reyes-Gavilán CG, Gueimonde M. 2012. Facultative to strict anaerobes ratio in the preterm infant microbiota: a target for intervention? Gut Microbes 3:583–588. http://dx.doi.org/10.4161/gmic.21942
46. Sela DA, Mills DA. 2010. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol 18:298–307. http://dx.doi.org/10.1016/j.tim.2010.03.008
47. Sonnenburg JL, Chen CT, Gordon JI. 2006. Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host. PLoS Biol 4:e413. http://dx.doi.org/10.1371/journal.pbio.0040413
48. Milani C, Lugli GA, Duranti S, Turroni F, Mancabelli L, Ferrario C, Mangifesta M, Hevia A, Viappiani A, Scholz M, Arioli S, Sanchez B, Lane J, Ward DV, Hickey R, Mora D, Segata N, Margolles A, van Sinderen D, Ventura M. 2015. Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut. Sci Rep 5:15782. http://dx.doi.org/10.1038/srep15782
49. Arboleya S, Salazar N, Solís G, Fernández N, Hernández-Barranco AM, Cuesta I, Gueimonde M, de los Reyes-Gavilán CG. 2013a. Assessment of intestinal microbiota modulation ability of Bifidobacterium strains in in vitro fecal batch cultures from preterm neonates. Anaerobe 19:9–16. http://dx.doi.org/10.1016/j.anaerobe.2012.11.001
50. Boto-Ordóñez M, Urpi-Sarda M, Queipo-Ortuño MI, Tulipani S, Tinahones FJ, Andres-Lacueva C. 2014. High levels of Bifidobacteria are associated with increased levels of anthocyanin microbial metabolites: a randomized clinical trial. Food Funct 5:1932–1938. http://dx.doi.org/10.1039/C4FO00029C [PubMed]
51. Enomoto T, Sowa M, Nishimori K, Shimazu S, Yoshida A, Yamada K, Furukawa F, Nakagawa T, Yanagisawa N, Iwabuchi N, Odamaki T, Abe F, Nakayama J, Xiao JZ. 2014. Effects of bifidobacterial supplementation to pregnant women and infants in the prevention of allergy development in infants and on fecal microbiota. Allergol Int 63:575–585. http://dx.doi.org/10.2332/allergolint.13-OA-0683
52. Monteagudo-Mera A, Arthur JC, Jobin C, Keku T, Bruno-Barcena JM, Azcarate-Peril MA. 2016. High purity galacto-oligosaccharides enhance specific Bifidobacterium species and their metabolic activity in the mouse gut microbiome. Benef Microbes 7:247–264. http://dx.doi.org/10.3920/BM2015.0114
53. Sugahara H, Odamaki T, Fukuda S, Kato T, Xiao JZ, Abe F, Kikuchi J, Ohno H. 2015. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community. Sci Rep 5:13548. http://dx.doi.org/10.1038/srep13548
54. Wu BB, Yang Y, Xu X, Wang WP. 2016. Effects of Bifidobacterium supplementation on intestinal microbiota composition and the immune response in healthy infants. World J Pediatr 12:177–182. http://dx.doi.org/10.1007/s12519-015-0025-3
55. Salazar N, Ruas-Madiedo P, Kolida S, Collins M, Rastall R, Gibson G, de Los Reyes-Gavilán CG. 2009. Exopolysaccharides produced by Bifidobacterium longum IPLA E44 and Bifidobacterium animalis subsp. lactis IPLA R1 modify the composition and metabolic activity of human faecal microbiota in pH-controlled batch cultures. Int J Food Microbiol 135:260–267. http://dx.doi.org/10.1016/j.ijfoodmicro.2009.08.017
56. Salazar N, Binetti A, Gueimonde M, Alonso A, Garrido P, González del Rey C, González C, Ruas-Madiedo P, de los Reyes-Gavilán CG. 2011. Safety and intestinal microbiota modulation by the exopolysaccharide-producing strains Bifidobacterium animalis IPLA R1 and Bifidobacterium longum IPLA E44 orally administered to Wistar rats. Int J Food Microbiol 144:342–351. http://dx.doi.org/10.1016/j.ijfoodmicro.2010.10.016
57. Rios-Covian D, Arboleya S, Hernandez-Barranco AM, Alvarez-Buylla JR, Ruas-Madiedo P, Gueimonde M, de los Reyes-Gavilan CG. 2013. Interactions between Bifidobacterium and Bacteroides species in cofermentations are affected by carbon sources, including exopolysaccharides produced by bifidobacteria. Appl Environ Microbiol 79:7518–7524. http://dx.doi.org/10.1128/AEM.02545-13
58. Rios-Covian D, Gueimonde M, Duncan SH, Flint HJ, de los Reyes-Gavilan CG. 2015. Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol Lett 362:fnv176. http://dx.doi.org/10.1093/femsle/fnv176
59. Rios-Covián D, Sánchez B, Salazar N, Martínez N, Redruello B, Gueimonde M, de Los Reyes-Gavilán CG. 2015. Different metabolic features of Bacteroides fragilis growing in the presence of glucose and exopolysaccharides of bifidobacteria. Front Microbiol 6:825. http://dx.doi.org/10.3389/fmicb.2015.00825
60. Jung TH, Jeon WM, Han KS. 2015. In vitro effects of dietary inulin on human fecal microbiota and butyrate production. J Microbiol Biotechnol 25:1555–1558. http://dx.doi.org/10.4014/jmb.1505.05078
61. Kato T, Fukuda S, Fujiwara A, Suda W, Hattori M, Kikuchi J, Ohno H. 2014. Multiple omics uncovers host-gut microbial mutualism during prebiotic fructooligosaccharide supplementation. DNA Res 21:469–480. http://dx.doi.org/10.1093/dnares/dsu013
62. Neyrinck AM, Possemiers S, Druart C, Van de Wiele T, De Backer F, Cani PD, Larondelle Y, Delzenne NM. 2011. Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice. PLoS One 6:e20944. http://dx.doi.org/10.1371/journal.pone.0020944
63. Rivière A, Gagnon M, Weckx S, Roy D, De Vuyst L. 2015. Mutual cross-feeding interactions between Bifidobacterium longum subsp. longum NCC2705 and Eubacterium rectale ATCC 33656 explain the bifidogenic and butyrogenic effects of arabinoxylan oligosaccharides. Appl Environ Microbiol 81:7767–7781. http://dx.doi.org/10.1128/AEM.02089-15
64. Falony G, Calmeyn T, Leroy F, De Vuyst L. 2009. Coculture fermentations of Bifidobacterium species and Bacteroides thetaiotaomicron reveal a mechanistic insight into the prebiotic effect of inulin-type fructans. Appl Environ Microbiol 75:2312–2319. http://dx.doi.org/10.1128/AEM.02649-08
65. De Vuyst L, Leroy F. 2011. Cross-feeding between bifidobacteria and butyrate-producing colon bacteria explains bifdobacterial competitiveness, butyrate production, and gas production. Int J Food Microbiol 149:73–80. http://dx.doi.org/10.1016/j.ijfoodmicro.2011.03.003
66. Ruiz L, Sánchez B, de Los Reyes-Gavilán CG, Gueimonde M, Margolles A. 2009. Coculture of Bifidobacterium longum and Bifidobacterium breve alters their protein expression profiles and enzymatic activities. Int J Food Microbiol 133:148–153. http://dx.doi.org/10.1016/j.ijfoodmicro.2009.05.014
67. Egan M, Motherway MO, Kilcoyne M, Kane M, Joshi L, Ventura M, van Sinderen D. 2014. Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium. BMC Microbiol 14:282. http://dx.doi.org/10.1186/s12866-014-0282-7
68. Tejero-Sariñena S, Barlow J, Costabile A, Gibson GR, Rowland I. 2013. Antipathogenic activity of probiotics against Salmonella Typhimurium and Clostridium difficile in anaerobic batch culture systems: is it due to synergies in probiotic mixtures or the specificity of single strains? Anaerobe 24:60–65. http://dx.doi.org/10.1016/j.anaerobe.2013.09.011
69. Yuan J, Wang B, Sun Z, Bo X, Yuan X, He X, Zhao H, Du X, Wang F, Jiang Z, Zhang L, Jia L, Wang Y, Wei K, Wang J, Zhang X, Sun Y, Huang L, Zeng M. 2008. Analysis of host-inducing proteome changes in bifidobacterium longum NCC2705 grown in vivo. J Proteome Res 7:375–385. http://dx.doi.org/10.1021/pr0704940
70. Ferrario C, Milani C, Mancabelli L, Lugli GA, Duranti S, Mangifesta M, Viappiani A, Turroni F, Margolles A, Ruas-Madiedo P, van Sinderen D, Ventura M. 2016. Modulation of the eps-ome transcription of bifidobacteria through simulation of human intestinal environment. FEMS Microbiol Ecol 92:fiw056. http://dx.doi.org/10.1093/femsec/fiw056
71. O’Connell Motherway M, Zomer A, Leahy SC, Reunanen J, Bottacini F, Claesson MJ, O’Brien F, Flynn K, Casey PG, Munoz JA, Kearney B, Houston AM, O’Mahony C, Higgins DG, Shanahan F, Palva A, de Vos WM, Fitzgerald GF, Ventura M, O’Toole PW, van Sinderen D. 2011. Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor. Proc Natl Acad Sci USA 108:11217–11222. http://dx.doi.org/10.1073/pnas.1105380108
72. Turroni F, Serafini F, Mangifesta M, Arioli S, Mora D, van Sinderen D, Ventura M. 2014. Expression of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in response to environmental gut conditions. FEMS Microbiol Lett 357:23–33. http://dx.doi.org/10.1111/1574-6968.12509
73. Arboleya S, Salazar N, Solís G, Fernández N, Gueimonde M, de los Reyes-Gavilán CG. 2013. In vitro evaluation of the impact of human background microbiota on the response to Bifidobacterium strains and fructo-oligosaccharides. Br J Nutr 110:2030–2036. http://dx.doi.org/10.1017/S0007114513001487
74. Senan S, Prajapati JB, Joshi CG, Sreeja V, Gohel MK, Trivedi S, Patel RM, Pandya H, Singh US, Phatak A, Patel HA. 2015. Geriatric respondents and non-respondents to probiotic intervention can be differentiated by inherent gut microbiome composition. Front Microbiol 6:944. http://dx.doi.org/10.3389/fmicb.2015.00944
75. Tojo R, Suárez A, Clemente MG, de los Reyes-Gavilán CG, Margolles A, Gueimonde M, Ruas-Madiedo P. 2014. Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. World J Gastroenterol 20:15163–15176. http://dx.doi.org/10.3748/wjg.v20.i41.15163
76. Reid G, Younes JA, Van der Mei HC, Gloor GB, Knight R, Busscher HJ. 2011. Microbiota restoration: natural and supplemented recovery of human microbial communities. Nat Rev Microbiol 9:27–38. http://dx.doi.org/10.1038/nrmicro2473
77. Food and Agriculture Organization. 2006. Probiotics in food: health and nutritional properties and guidelines for evaluation. FAO Food and Nutrition Paper 85. ISSN 0254-4725.
78. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. 2014. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11:506–514. http://dx.doi.org/10.1038/nrgastro.2014.66
79. Tissier H. 1906. Traitement des infections intestinales par la méthode de la flore bactérienne de l’intestin. Crit Rev Soc Biol 60:359–361.
80. Moro E. 1900. Über den Bacillus acidophilus. Jahrb Kinderheilkunde Physiche Erziehung 52:38–55.
81. Rettger LF, Cheplin HA. 1922. Bacillus acidophilus and its therapeutic application. Arch Intern Med (Chic) 29:357–367. Chic http://dx.doi.org/10.1001/archinte.1922.00110030082005
82. Vasiljevic T, Shah NP. 2008. Probiotics—from Metchnikoff to bioactives. Int Dairy J 18:714–728. http://dx.doi.org/10.1016/j.idairyj.2008.03.004
83. EFSA, European Food Safety Authority. 2015. Statement on the update of the list of QPS-recommended biological agents intentionally added to food or feed as notified to EFSA. 2: Suitability of taxonomic units notified to EFSA until March 2015. EFSA J 13:4138.
84. Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A. 2009. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol 104:437–443. http://dx.doi.org/10.1038/ajg.2008.118 [PubMed]
85. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P, Campieri M, Kamm MA. 2004. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53:108–114. http://dx.doi.org/10.1136/gut.53.1.108
86. Kajander K, Myllyluoma E, Rajilić-Stojanović M, Kyrönpalo S, Rasmussen M, Järvenpää S, Zoetendal EG, de Vos WM, Vapaatalo H, Korpela R. 2008. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther 27:48–57. http://dx.doi.org/10.1111/j.1365-2036.2007.03542.x
87. O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, O’Sullivan GC, Kiely B, Collins JK, Shanahan F, Quigley EM. 2005. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128:541–551. http://dx.doi.org/10.1053/j.gastro.2004.11.050
88. Almeida CC, Lorena SL, Pavan CR, Akasaka HM, Mesquita MA. 2012. Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients. Nutr Clin Pract 27:247–251. http://dx.doi.org/10.1177/0884533612440289
89. Bogsan CSB, Ferreira L, Maldonado C, Perdigon G, Almeida SR, Oliveira MN. 2014. Fermented or unfermented milk using Bifidobacterium animalis subsp. lactis HN019: technological approach determines the probiotic modulation of mucosal cellular immunity. Food Res Int 64:283–288. http://dx.doi.org/10.1016/j.foodres.2014.05.036
90. Reid G. 2015. The growth potential for dairy probiotics. Int Dairy J 49:16–22. http://dx.doi.org/10.1016/j.idairyj.2015.04.004
91. Marsh AJ, Hill C, Ross RP, Cotter PD. 2014. Fermented beverages with health-promoting potential: past and future perspectives. Trends Food Sci Technol 38:113–124. http://dx.doi.org/10.1016/j.tifs.2014.05.002
92. Prasanna PHP, Grandison AS, Charalampopoulos D. 2014. Bifidobacteria in milk products: an overview of physiological and biochemical properties, exopolysaccharide production, selection criteria of milk products and health benefits. Food Res Int 55:247–262. http://dx.doi.org/10.1016/j.foodres.2013.11.013
93. Janer C, Arigoni F, Lee BH, Peláez C, Requena T. 2005. Enzymatic ability of Bifidobacterium animalis subsp. lactis to hydrolyze milk proteins: identification and characterization of endopeptidase O. Appl Environ Microbiol 71:8460–8465. http://dx.doi.org/10.1128/AEM.71.12.8460-8465.2005
94. Kehagias C, Csapó J, Konteles S, Kolokitha E, Koulouris S, Csapó-Kiss Z. 2008. Support of growth and formation of D-amino acids by Bifidobacterium longum in cows’, ewes’, goats’ milk and modified whey powder products. Int Dairy J 18:396–402. http://dx.doi.org/10.1016/j.idairyj.2007.11.014
95. Turroni F, Foroni E, Serafini F, Viappiani A, Montanini B, Bottacini F, Ferrarini A, Bacchini PL, Rota C, Delledonne M, Ottonello S, van Sinderen D, Ventura M. 2011. Ability of Bifidobacterium breve to grow on different types of milk: exploring the metabolism of milk through genome analysis. Appl Environ Microbiol 77:7408–7417. http://dx.doi.org/10.1128/AEM.05336-11
96. Serafini F, Turroni F, Ruas-Madiedo P, Lugli GA, Milani C, Duranti S, Zamboni N, Bottacini F, van Sinderen D, Margolles A, Ventura M. 2014. Kefir fermented milk and kefiran promote growth of Bifidobacterium bifidum PRL2010 and modulate its gene expression. Int J Food Microbiol 178:50–59. http://dx.doi.org/10.1016/j.ijfoodmicro.2014.02.024
97. Hickey CD, Sheehan JJ, Wilkinson MG, Auty MA. 2015. Growth and location of bacterial colonies within dairy foods using microscopy techniques: a review. Front Microbiol 6:99. http://dx.doi.org/10.3389/fmicb.2015.00099
98. de los Reyes-Gavilán CG, Suárez A, Fernández-García M, Margolles A, Gueimonde M, Ruas-Madiedo P. 2011. Adhesion of bile-adapted Bifidobacterium strains to the HT29-MTX cell line is modified after sequential gastrointestinal challenge simulated in vitro using human gastric and duodenal juices. Res Microbiol 162:514–519. http://dx.doi.org/10.1016/j.resmic.2011.03.009
99. Veiga P, Pons N, Agrawal A, Oozeer R, Guyonnet D, Brazeilles R, Faurie JM, van Hylckama Vlieg JET, Houghton LA, Whorwell PJ, Ehrlich SD, Kennedy SP. 2014. Changes of the human gut microbiome induced by a fermented milk product. Sci Rep 4:6328. http://dx.doi.org/10.1038/srep06328
100. Gonzalez-Gonzalez C, Gibson T, Jauregi P. 2013. Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory peptides produced by Bifidobacterium bifidum MF 20/5. Int J Food Microbiol 167:131–137. http://dx.doi.org/10.1016/j.ijfoodmicro.2013.09.002
101. Lewis ZT, Shani G, Masarweh CF, Popovic M, Frese SA, Sela DA, Underwood MA, Mills DA. 2016. Validating bifidobacterial species and subspecies identity in commercial probiotic products. Pediatr Res 79:445–452. http://dx.doi.org/10.1038/pr.2015.244
102. Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, Turroni F, González S, Suárez A, Gueimonde M, Ventura M, Sánchez B, Margolles A. 2014. Intestinal dysbiosis associated with systemic lupus erythematosus. MBio 5:e01548-14. http://dx.doi.org/10.1128/mBio.01548-14
103. Dinan TG, Cryan JF. 2017. Microbes, immunity and behaviour: psychoneuroimmunology meets the microbiome. Neuropsychopharmacology 42:178–192. [PubMed]
104. López P, González-Rodríguez I, Sánchez B, Gueimonde M, Margolles A, Suárez A. 2012. Treg-inducing membrane vesicles from Bifidobacterium bifidum LMG13195 as potential adjuvants in immunotherapy. Vaccine 30:825–829. http://dx.doi.org/10.1016/j.vaccine.2011.11.115
105. López P, de Paz B, Rodríguez-Carrio J, Hevia A, Sánchez B, Margolles A, Suárez A. 2016. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 6:24072. http://dx.doi.org/10.1038/srep24072
106. Sanders ME, Guarner F, Guerrant R, Holt PR, Quigley EMM, Sartor RB, Sherman PM, Mayer EA. 2013. An update on the use and investigation of probiotics in health and disease. Gut 62:787–796. http://dx.doi.org/10.1136/gutjnl-2012-302504 [PubMed]
107. WGO. 2011. World Gastroenterology Organisation Global Guidelines: Probiotics and Prebiotics: http://www.worldgastroenterology.org/probiotics-prebiotics.html
108. He T, Priebe MG, Zhong Y, Huang C, Harmsen HJM, Raangs GC, Antoine JM, Welling GW, Vonk RJ. 2008. Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose-intolerant subjects. J Appl Microbiol 104:595–604. [PubMed]
109. Weizman Z, Asli G, Alsheikh A. 2005. Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics 115:5–9. http://dx.doi.org/10.1542/peds.2004-1815
110. Corrêa NB, Péret Filho LA, Penna FJ, Lima FM, Nicoli JR. 2005. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants. J Clin Gastroenterol 39:385–389. http://dx.doi.org/10.1097/01.mcg.0000159217.47419.5b
111. Selinger CP, Bell A, Cairns A, Lockett M, Sebastian S, Haslam N. 2013. Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind, randomized, placebo-controlled clinical trial. J Hosp Infect 84:159–165. http://dx.doi.org/10.1016/j.jhin.2013.02.019
112. Plummer S, Weaver MA, Harris JC, Dee P, Hunter J. 2004. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Int Microbiol 7:59–62. [PubMed]
113. Goldenberg JZ, Ma SS, Saxton JD, Martzen MR, Vandvik PO, Thorlund K, Guyatt GH, Johnston BC. 2013. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 5:CD006095.
114. Agrawal M, Aroniadis OC, Brandt LJ, Kelly C, Freeman S, Surawicz C, Broussard E, Stollman N, Giovanelli A, Smith B, Yen E, Trivedi A, Hubble L, Kao D, Borody T, Finlayson S, Ray A, Smith R. 2016. The long-term efficacy and safety of fecal microbiota transplant for recurrent, severe, and complicated Clostridium difficile infection in 146 elderly individuals. J Clin Gastroenterol 50:403–407. [PubMed]
115. Khoruts A, Sadowsky MJ. 2016. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol 13:508–516. http://dx.doi.org/10.1038/nrgastro.2016.98
116. Hevia A, Delgado S, Margolles A, Sánchez B. 2015. Application of density gradient for the isolation of the fecal microbial stool component and the potential use thereof. Sci Rep 5:16807. http://dx.doi.org/10.1038/srep16807
117. Li BZ, Threapleton DE, Wang JY, Xu JM, Yuan JQ, Zhang C, Li P, Ye QL, Guo B, Mao C, Ye DQ. 2015. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ 351:h4052. http://dx.doi.org/10.1136/bmj.h4052
118. Boltin D. 2016. Probiotics in Helicobacter pylori-induced peptic ulcer disease. Best Pract Res Clin Gastroenterol 30:99–109. http://dx.doi..org/10.1016/j.bpg.2015.12.003 [PubMed]
119. Talebi Bezmin Abadi A. 2016. Vaccine against Helicobacter pylori: inevitable approach. World J Gastroenterol 22:3150–3157. http://dx.doi.org/10.3748/wjg.v22.i11.3150 [PubMed]
120. Lu C, Sang J, He H, Wan X, Lin Y, Li L, Li Y, Yu C. 2016. Probiotic supplementation does not improve eradication rate of Helicobacter pylori infection compared to placebo based on standard therapy: a meta-analysis. Sci Rep 6:23522. http://dx.doi.org/10.1038/srep23522
121. Miki K, Urita Y, Ishikawa F, Iino T, Shibahara-Sone H, Akahoshi R, Mizusawa S, Nose A, Nozaki D, Hirano K, Nonaka C, Yokokura T. 2007. Effect of Bifidobacterium bifidum fermented milk on Helicobacter pylori and serum pepsinogen levels in humans. J Dairy Sci 90:2630–2640. http://dx.doi.org/10.3168/jds.2006-803
122. Sheu BS, Cheng HC, Kao AW, Wang ST, Yang YJ, Yang HB, Wu JJ. 2006. Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy. Am J Clin Nutr 83:864–869. [PubMed]
123. Wang KY, Li SN, Liu CS, Perng DS, Su YC, Wu DC, Jan CM, Lai CH, Wang TN, Wang WM. 2004. Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am J Clin Nutr 80:737–741. [PubMed]
124. Raisch J, Rolhion N, Dubois A, Darfeuille-Michaud A, Bringer MA. 2015. Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression. Lab Invest 95:296–307. http://dx.doi.org/10.1038/labinvest.2014.161
125. Yu J, Chen Y, Fu X, Zhou X, Peng Y, Shi L, Chen T, Wu Y. 2016. Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway. Int J Cancer 139:1318–1326. http://dx.doi.org/10.1002/ijc.30168
126. Roller M, Clune Y, Collins K, Rechkemmer G, Watzl B. 2007. Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients. Br J Nutr 97:676–684. http://dx.doi.org/10.1017/S0007114507450292 [PubMed]
127. Worthley DL, Le Leu RK, Whitehall VL, Conlon M, Christophersen C, Belobrajdic D, Mallitt KA, Hu Y, Irahara N, Ogino S, Leggett BA, Young GP. 2009. A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and synbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer. Am J Clin Nutr 90:578–586. http://dx.doi.org/10.3945/ajcn.2009.28106
128. Rafter J, Bennett M, Caderni G, Clune Y, Hughes R, Karlsson PC, Klinder A, O’Riordan M, O’Sullivan GC, Pool-Zobel B, Rechkemmer G, Roller M, Rowland I, Salvadori M, Thijs H, Van Loo J, Watzl B, Collins JK. 2007. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 85:488–496. [PubMed]
129. Liu ZH, Huang MJ, Zhang XW, Wang L, Huang NQ, Peng H, Lan P, Peng JS, Yang Z, Xia Y, Liu WJ, Yang J, Qin HL, Wang JP. 2013. The effects of perioperative probiotic treatment on serum zonulin concentration and subsequent postoperative infectious complications after colorectal cancer surgery: a double-center and double-blind randomized clinical trial. Am J Clin Nutr 97:117–126. http://dx.doi.org/10.3945/ajcn.112.040949
130. Liu Z, Li C, Huang M, Tong C, Zhang X, Wang L, Peng H, Lan P, Zhang P, Huang N, Peng J, Wu X, Luo Y, Qin H, Kang L, Wang J. 2015. Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial. BMC Gastroenterol 15:34. http://dx.doi.org/10.1186/s12876-015-0260-z
131. Zhang JW, Du P, Gao J, Yang BR, Fang WJ, Ying CM. 2012. Preoperative probiotics decrease postoperative infectious complications of colorectal cancer. Am J Med Sci 343:199–205. http://dx.doi.org/10.1097/MAJ.0b013e31823aace6 [PubMed]
132. Wada M, Nagata S, Saito M, Shimizu T, Yamashiro Y, Matsuki T, Asahara T, Nomoto K. 2010. Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies. Support Care Cancer 18:751–759. http://dx.doi.org/10.1007/s00520-009-0711-6 [PubMed]
133. Ambalam P, Raman M, Purama RK, Doble M. 2016. Probiotics, prebiotics and colorectal cancer prevention. Best Pract Res Clin Gastroenterol 30:119–131. http://dx.doi.org/10.1016/j.bpg.2016.02.009
134. Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. 2013. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol 19:6911–6918. http://dx.doi.org/10.3748/wjg.v19.i40.6911
135. Lo RS, Austin AS, Freeman JG. 2014. Is there a role for probiotics in liver disease? Scientific World Journal 2014:874768. http://dx.doi.org/10.1155/2014/874768
136. Waller PA, Gopal PK, Leyer GJ, Ouwehand AC, Reifer C, Stewart ME, Miller LE. 2011. Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults. Scand J Gastroenterol 46:1057–1064. http://dx.doi.org/10.3109/00365521.2011.584895 [PubMed]
137. Agrawal A, Houghton LA, Morris J, Reilly B, Guyonnet D, Goupil Feuillerat N, Schlumberger A, Jakob S, Whorwell PJ. 2009. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther 29:104–114. http://dx.doi.org/10.1111/j.1365-2036.2008.03853.x
138. Guyonnet D, Chassany O, Ducrotte P, Picard C, Mouret M, Mercier CH, Matuchansky C. 2007. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment Pharmacol Ther 26:475–486. http://dx.doi.org/10.1111/j.1365-2036.2007.03362.x
139. Groeger D, O’Mahony L, Murphy EF, Bourke JF, Dinan TG, Kiely B, Shanahan F, Quigley EM. 2013. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 4:325–339. http://dx.doi.org/10.4161/gmic.25487
140. Kajander K, Hatakka K, Poussa T, Färkkilä M, Korpela R. 2005. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther 22:387–394. http://dx.doi.org/10.1111/j.1365-2036.2005.02579.x
141. Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EM. 2010. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 59:325–332. http://dx.doi.org/10.1136/gut.2008.167270
142. Guandalini S, Magazzù G, Chiaro A, La Balestra V, Di Nardo G, Gopalan S, Sibal A, Romano C, Canani RB, Lionetti P, Setty M. 2010. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr 51:24–30. http://dx.doi.org/10.1097/MPG.0b013e3181ca4d95
143. Distrutti E, Monaldi L, Ricci P, Fiorucci S. 2016. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol 22:2219–2241. [PubMed]
144. Sood A, Midha V, Makharia GK, Ahuja V, Singal D, Goswami P, Tandon RK. 2009. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol 7:1202–1209.e1. http://dx.doi.org/10.1016/j.cgh.2009.07.016
145. Tursi A, Brandimarte G, Papa A, Giglio A, Elisei W, Giorgetti GM, Forti G, Morini S, Hassan C, Pistoia MA, Modeo ME, Rodino’ S, D’Amico T, Sebkova L, Sacca’ N, Di Giulio E, Luzza F, Imeneo M, Larussa T, Di Rosa S, Annese V, Danese S, Gasbarrini A. 2010. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 105:2218–2227. http://dx.doi.org/10.1038/ajg.2010.218
146. Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, Oh W. 2005. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 115:1–4. http://dx.doi.org/10.1542/peds.2004-1463 [PubMed]
147. Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, Tsao LY, Chen CH, Su BH. 2008. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics 122:693–700. http://dx.doi.org/10.1542/peds.2007-3007
148. Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, Hammerman C. 2005. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 147:192–196. http://dx.doi.org/10.1016/j.jpeds.2005.03.054
149. Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR, Probiotics in Preterm Infants Study Collaborative Group. 2016. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet 387:649–660. http://dx.doi.org/10.1016/S0140-6736(15)01027-2
150. Zuercher AW, Fritsché R, Corthésy B, Mercenier A. 2006. Food products and allergy development, prevention and treatment. Curr Opin Biotechnol 17:198–203. http://dx.doi.org/10.1016/j.copbio.2006.01.010
151. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. 2010. Role of Treg in immune regulation of allergic diseases. Eur J Immunol 40:1232–1240. http://dx.doi.org/10.1002/eji.200940045
152. Toh ZQ, Anzela A, Tang MLK, Licciardi PV. 2012. Probiotic therapy as a novel approach for allergic disease. Front Pharmacol 3:171. http://dx.doi.org/10.3389/fphar.2012.00171
153. Sistek D, Kelly R, Wickens K, Stanley T, Fitzharris P, Crane J. 2006. Is the effect of probiotics on atopic dermatitis confined to food sensitized children? Clin Exp Allergy 36:629–633. http://dx.doi.org/10.1111/j.1365-2222.2006.02485.x
154. Gerasimov SV, Vasjuta VV, Myhovych OO, Bondarchuk LI. 2010. Probiotic supplement reduces atopic dermatitis in preschool children: a randomized, double-blind, placebo-controlled, clinical trial. Am J Clin Dermatol 11:351–361. http://dx.doi.org/10.2165/11531420-000000000-00000
155. Yeşilova Y, Çalka Ö, Akdeniz N, Berktaş M. 2012. Effect of probiotics on the treatment of children with atopic dermatitis. Ann Dermatol 24:189–193. http://dx.doi.org/10.5021/ad.2012.24.2.189
156. van der Aa LB, Heymans HS, van Aalderen WM, Sillevis Smitt JH, Knol J, Ben Amor K, Goossens DA, Sprikkelman AB, Synbad Study Group. 2010. Effect of a new synbiotic mixture on atopic dermatitis in infants: a randomized-controlled trial. Clin Exp Allergy 40:795–804.
157. Singh A, Hacini-Rachinel F, Gosoniu ML, Bourdeau T, Holvoet S, Doucet-Ladeveze R, Beaumont M, Mercenier A, Nutten S. 2013. Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial. Eur J Clin Nutr 67:161–167. http://dx.doi.org/10.1038/ejcn.2012.197
158. Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Iwatsuki K, Kokubo S, Togashi H, Enomoto K, Enomoto T. 2006. Effect of probiotic Bifidobacterium longum BB536 [corrected] in relieving clinical symptoms and modulating plasma cytokine levels of Japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial. J Investig Allergol Clin Immunol 16:86–93. [PubMed]
159. Huurre A, Laitinen K, Rautava S, Korkeamari M, Isoulari E. 2008. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensibilization: a double-blind placebo-controlled study. Clin Exp Allergy 38:1342–1348. http://dx.doi.org/10.1111/j.1365-2222.2008.03008.x
160. Dotterud CK, Storrø O, Johnsen R, Oien T. 2010. Probiotics in pregnant women to prevent allergic disease: a randomized, double-blind trial. Br J Dermatol 163:616–623. http://dx.doi.org/10.1111/j.1365-2133.2010.09889.x
161. Wickens K, Black PN, Stanley TV, Mitchell E, Fitzharris P, Tannock GW, Purdie G, Crane J, Probiotic Study Group. 2008. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 122:788–794. http://dx.doi.org/10.1016/j.jaci.2008.07.011
162. Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M. 2007. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 119:192–198. http://dx.doi.org/10.1016/j.jaci.2006.09.009
163. Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO, Lee SY, Ahn KM, Ji GE. 2010. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Pediatr Allergy Immunol 21(2p2):e386–e393. http://dx.doi.org/10.1111/j.1399-3038.2009.00958.x
164. Niers L, Martín R, Rijkers G, Sengers F, Timmerman H, van Uden N, Smidt H, Kimpen J, Hoekstra M. 2009. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy 64:1349–1358. http://dx.doi.org/10.1111/j.1398-9995.2009.02021.x
165. Soh SE, Aw M, Gerez I, Chong YS, Rauff M, Ng YP, Wong HB, Pai N, Lee BW, Shek LP. 2009. Probiotic supplementation in the first 6 months of life in at risk Asian infants--effects on eczema and atopic sensitization at the age of 1 year. Clin Exp Allergy 39:571–578. http://dx.doi.org/10.1111/j.1365-2222.2008.03133.x
166. Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, Beyer K, Burks W, Canonica GW, Ebisawa M, Gandhi S, Kamenwa R, Lee BW, Li H, Prescott S, Riva JJ, Rosenwasser L, Sampson H, Spigler M, Terracciano L, Vereda-Ortiz A, Waserman S, Yepes-Nuñez JJ, Brożek JL, Schünemann HJ. 2015. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): probiotics. World Allergy Organ J 8:4. http://dx.doi.org/10.1186/s40413-015-0055-2
167. Ruas-Madiedo P, Zoon P. 2003. Effect of exopolysaccharide-producing Lactococcus lactis strains and temperature on the permeability of skim milk gels. Colloids Surf A Physicochem Eng Asp 213:245–253. http://dx.doi.org/10.1016/S0927-7757(02)00517-4
168. Marteau P, Guyonnet D, Lafaye de Micheaux P, Gelu S. 2013. A randomized, double-blind, controlled study and pooled analysis of two identical trials of fermented milk containing probiotic Bifidobacterium lactis CNCM I-2494 in healthy women reporting minor digestive symptoms. Neurogastroenterol Motil 25:331–e252. http://dx.doi.org/10.1111/nmo.12078
169. Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O’Mahony L, Kiely B, Shanahan F, Quigley EM. 2006. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol 101:1581–1590. http://dx.doi.org/10.1111/j.1572-0241.2006.00734.x
170. Drouault-Holowacz S, Bieuvelet S, Burckel A, Cazaubiel M, Dray X, Marteau P. 2008. A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol 32:147–152. http://dx.doi.org/10.1016/j.gcb.2007.06.001
171. Ishikawa H, Matsumoto S, Ohashi Y, Imaoka A, Setoyama H, Umesaki Y, Tanaka R, Otani T. 2011. Beneficial effects of probiotic bifidobacterium and galacto-oligosaccharide in patients with ulcerative colitis: a randomized controlled study. Digestion 84:128–133. http://dx.doi.org/10.1159/000322977 [PubMed]
172. Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M. 2003. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124:1202–1209. http://dx.doi.org/10.1016/S0016-5085(03)00171-9
173. Pronio A, Montesani C, Butteroni C, Vecchione S, Mumolo G, Vestri A, Vitolo D, Boirivant M. 2008. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis 14:662–668. http://dx.doi.org/10.1002/ibd.20369

Citations loading...


Article metrics loading...



Bifidobacteria are members of the intestinal microbiota of mammals and other animals, and some strains are able to exert health-promoting effects. The genus belongs to the phylum. , , and constitute the most abundant phyla in the human intestinal microbiota, and being predominant in adults, and in breast-fed infants, where bifidobacteria can reach levels higher than 90% of the total bacterial population. They are among the first microbial colonizers of the intestines of newborns, and play key roles in the development of their physiology, including maturation of the immune system and use of dietary components. Indeed, some nutrients, such as human milk oligosaccharides, are important drivers of bifidobacterial development. Some strains are considered probiotic microorganisms because of their beneficial effects, and they have been included as bioactive ingredients in functional foods, mainly dairy products, as well as in food supplements and pharma products, alone, or together with, other microbes or microbial substrates. Well-documented scientific evidence of their activities is currently available for bifidobacteria-containing preparations in some intestinal and extraintestinal pathologies. In this review, we focus on the role of bifidobacteria as members of the human intestinal microbiota and their use as probiotics in the prevention and treatment of disease.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Positive effects of some strains on gastrointestinal functions studied by means of human intervention studies.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0010-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Visualization of subsp. growth in skimmed milk by using confocal scanner laser microcopy. The staining method was previously reported by Ruas-Madiedo and Zoon ( 167 ); in short, two dyes, rhodamine B (which dyes proteins) and acridine orange (which dyes nucleic acids), were added to the milk at final concentration of 0.001 and 0.002%, respectively. Afterward, stained milk was inoculated (5%) and carefully placed into high-optical-quality plastic μ-Slides (Ibidi GmbH) for direct confocal laser scanning microscopy analysis. The microplates were incubated at 37°C until they reached a pH of ≤4.5, and the confocal microscope Ultra-Spectral Leica TCS AOBS SP2 (Leica Microsystems GmbH, located in the University of Oviedo facilities) was used. Bacteria dyed with acridine orange were visualized with the laser 488 nm ion argon/krypton (green), and proteins (mainly caseins) dyed with rhodamine B were visualized with the laser 543 nm He/Ne (red) but also with the laser 488 nm. Thus, after image treatment, the bacteria are visualized in green and the casein matrix in yellow (combination red and green). The oil immersion objective 63×/1.40 combined with an amplification zoom of 1.58 was directly used (×100 magnification). Microphotographs: a Z-projection (thickness about 10 μm) of 10 slides of an XY-field (bar, 10 μm); a slide of an XY-field (bar, 10 μm); an optical zoom of a region inside the XY-field showed in B (bar, 5 μm).

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0010-2016
Permissions and Reprints Request Permissions
Download as Powerpoint


Generic image for table

strains used as probiotics with demonstrated effectivity in humans trials

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0010-2016
Generic image for table

Selection of meta-analyses and reviews about the effect of probiotic products containing bifidobacteria on certain diseases

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0010-2016

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error