Abstract
To determine whether the size of the intestinal bifidobacterial population can influence the immune response to poliovirus vaccination in infants, we set up a randomized, placebo-controlled trial. From birth to 4 mo, infants were given a fermented infant formula (FIF) or a standard formula (placebo). Bifidobacteria were quantified monthly in infant stools. Antipoliovirus IgA response to Pentacoq® was assessed before and 1 mo after the second vaccine injection. Thirty infants were randomized, and 20 completed the study (nine in the placebo group and 11 in the FIF group). Fecal bifidobacterial level was significantly higher with the FIF group at 4 mo of age (p = 0.0498). Furthermore, B. longum/B. infantis carriage was higher at 4 mo in the FIF group (p = 0.0399). Antipoliovirus IgA titers increased after Pentacoq® challenge (p < 0.001), and the rise was significantly higher in the FIF group (p < 0.02). Antibody titers correlated with bifidobacteria, especially with B. longum/B. infantis and B. breve levels (p < 0.002). Infants who harbored B. longum/B. infantis also exhibited higher levels of antipoliovirus IgAs (p < 0.002). In conclusion, the present results indicate that antipoliovirus response can be triggered with a fermented formula that is able to favor intestinal bifidobacteria. Whether this effect on the immune system is achieved through the bifidogenic effect of the formula (mainly through B. longum/B. infantis and B. breve stimulation) or directly linked to compounds (i.e. peptides) produced by milk fermentation remains to be investigated.
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Abbreviations
- FIF:
-
fermented infant formula
- IPV:
-
inactivated poliovirus vaccine
References
Goldman AS 1993 The immune system of human milk: antimicrobial, antiinflammatory and immunomodulating properties. Pediatr Infect Dis J 12: 664–671
Davidson LA, Lonnerdal BO 1987 Persistence of human milk proteins in the breast-fed infant. Acta Paediatr Scand 76: 733–740
Vassilev TL, Veleva KV 1996 Natural polyreactive IgA and IgM autoantibodies in human colostrum. Scand J Immunol 44: 535–539
Jatsyk GV, Kuvaeva IB, Gribakin SG 1985 Immunological protection of the neonatal gastrointestinal tract: the importance of breast feeding. Acta Paediatr Scand 74: 246–249
Biavati B, Castagnoli P, Crociani F, Trovatelli LD 1984 Species of the Bifidobacterium in the feces of infants. Microbiologica 7: 341–345
Benno Y, Sawada K, Mitsuoka T 1984 The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol 28: 975–986
Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, Welling GW 2000 Analysis of the intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr 28: 19–25
Moreau MC 1998 Modulating properties of intestinal bacterial strains, E. coli and Bifidobacterium on two specific immune responses generated by the gut, i.e. oral tolerance to ovalbumin and intestinal IgA anti-rotavirus response in gnotobiotic animals. In: Talwar GP, Nath I (eds) 10th International Congress of Immunology. Bologna, Monduzzi Editore, pp 407–411
Romond MB, Ais A, Yazourh A, Romond C 1997 Cell-free wheys from bifidobacteria fermented milks exert a regulatory effect on the intestinal microflora of mice and humans. Anaerobe 3: 137–143
Romond MB, Ais A, Guillemot F, Bounouader R, Cortot A, Romond C 1998 Cell-free whey from Bifidobacterium breve C50 fermented milk modifies the colonic microflora in healthy subjects. J Dairy Sci 81: 1229–1235
Carlsson B, Zaman S, Mellander L, Jalil F, Hanson LA 1985 Secretory and serum immunoglobulin class-specific antibodies to poliovirus after vaccination. J Infect Dis 152: 1238–1244
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ 1951 Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Holdeman LV, Good IJ, Moore WE 1976 Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress. Appl Environ Microbiol 31: 359–375
Mullié C, Odou MF, Singer E, Romond MB, Izard D 2003 Multiplex PCR using 16S rRNA gene-targeted primers for the identification of bifidobacteria from human origin. FEMS Microbiol Lett 222: 129–136
Pickering LK, Granoff DM, Erickson JR, Masor ML, Cordle CT, Schaller JP, Winship TR, Paule CL, Hilty MD 1998 Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics 101: 242–249
Hahn-Zoric M, Carlsson B, Jeansson S, Ekre HP, Osterhaus AD, Roberton D, Hanson LA 1993 Anti-idiotypic antibodies to poliovirus antibodies in commercial immunoglobulin preparations, human serum, and milk. Pediatr Res 33: 475–480
Riordan SM, McIver CJ, Wakefield D, Thomas MC, Duncombe VM, Bolin TD 1999 Serum immunoglobulin and soluble IL-2 receptor levels in small intestinal overgrowth with indigenous gut flora. Dig Dis Sci 44: 939–944
Ouwehand A, Isolauri E, Salminen S 2002 The role of the intestinal microflora for the development of the immune system in early childhood. Eur J Nutr 41( suppl 1): I32–I37
Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL 2004 Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 172: 1118–24
Vinderola CG, Medici M, Perdigon G 2004 Relationship between interaction sites in the gut, hydrophobicity, mucosal immunomodulating capacities and cell wall protein profiles in indigenous and exogenous bacteria. J Appl Microbiol 96: 230–243
Schiffrin EJ, Blum S 2002 Interactions between the microbiota and the intestinal mucosa. Eur J Clin Nutr 56: S60–S64
LeBlanc JG, Matar C, Valdéz JC, LeBlanc J, Perdigon G 2002 Immunomodulating effects of peptidic fractions issued from milk fermented with Lactobacillus helveticus.. J Dairy Sci 85: 2733–2742
Buisman AM, Sonsma JA, Kimman TG, Koopmans MPG 2000 Mucosal and systemic immunity against poliovirus in mice transgenic for the poliovirus receptor: the poliovirus receptor is necessary for a virus-specific mucosal IgA response. J Infect Dis 181: 815–823
Herremans TM, Reimerink JH, Buisman AM, Kimman TG, Koopmans MP 1999 Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus. J Immunol 162: 5011–5018
Buisman AM, Sonsma JA, van Wijk MG, Vermeulen JP, Roholl PJ, Kimman TG 2003 Pathogenesis of poliovirus infection in PVRTg mice: poliovirus replicates in peritoneal macrophages. J Gen Virol 84: 2819–2828
Yasui H, Ohwaki M 1991 Enhancement of immune response in Peyer's patch cells cultured with Bifidobacterium breve.. J Dairy Sci 74: 1187–1195
Yasui H, Nagaoka N, Hayawaka K 1994 Augmentation of anti-influenza virus hemagglutinin antibody production by Peyer's patch cells with Bifidobacterium breve YIT4064. Clin Diagn Lab Immunol 1: 244–246
Heine W, Mohr C, Wutzke KD, Radke M 1991 Symbiotic interactions between colonic microflora and protein metabolism in infants. Acta Paediatr Scand 80: 7–12
Park JH, Um JI, Lee BJ, Goh JS, Park SY, Kim WS, Kim PH 2002 Encapsulated Bifidobacterium bifidum potentiates intestinal IgA production. Cell Immunol 219: 22–27
Hexham JM, Carayannopoulos L, Capra JD 1997 Structure and function in IgA. Chem Immunol 65: 73–87
Acknowledgements
We thank Dr. Menet and the pediatricians at the Maternité de la Sainte Famille for contribution to newborn inclusions and monthly consultations. We also thank Patrick Devos for providing statistical advice and carrying out part of the statistical analysis, Nathalie Derensy and Fatiha N'Zerwalt for skillful technical assistance, and Cécile Aubert-Jacquin for her help in preparing the manuscript.
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Mullié, C., Yazourh, A., Thibault, H. et al. Increased Poliovirus-Specific Intestinal Antibody Response Coincides with Promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial. Pediatr Res 56, 791–795 (2004). https://doi.org/10.1203/01.PDR.0000141955.47550.A0
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DOI: https://doi.org/10.1203/01.PDR.0000141955.47550.A0
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