• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of archdischfnLink to Publisher's site
Arch Dis Child Fetal Neonatal Ed. Nov 2000; 83(3): F186–F192.
PMCID: PMC1721174

Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months

Abstract

AIM—To evaluate the role of intestinal microflora and early formula feeding in the maturation of humoral immunity in healthy newborn infants.
STUDY DESIGN—Sixty four healthy infants were studied. Faecal colonisation with Bacteroides fragilis group, Bifidobacterium-like, and Lactobacillus-like bacteria was examined at 1, 2, and 6 months of age, and also the number of IgA-secreting, IgM-secreting, and IgG-secreting cells (detected by ELISPOT) at 0, 2, and 6 months of age.
RESULTS—Intestinal colonisation with bacteria from the B fragilis group was more closely associated with maturation of IgA-secreting and IgM-secreting cells than colonisation with the other bacterial genera studied or diet. Infants colonised with B fragilis at 1month of age had more IgA-secreting and IgM-secreting cells/106 mononuclear cells at 2 months of age (geometric mean (95% confidence interval) 1393 (962 to 2018) and 754 (427 to 1332) respectively) than infants not colonised (1015 (826 to 1247) and 394 (304 to 511) respectively); p = 0.04 and p = 0.009 respectively.
CONCLUSIONS—The type of bacteria colonising the intestine of newborns and the timing may determine the immunomodulation of the naive immune system.

Full Text

The Full Text of this article is available as a PDF (183K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mestecky J. The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol. 1987 Jul;7(4):265–276. [PubMed]
  • MacDonald TT. Development of mucosal immune function in man: potential for GI disease states. Acta Paediatr Jpn. 1994 Oct;36(5):532–536. [PubMed]
  • Savilahti E. Immunoglobulin-containing cells in the intestinal mucosa and immunoglobulins in the intestinal juice in children. Clin Exp Immunol. 1972 Jul;11(3):415–425. [PMC free article] [PubMed]
  • Burgio GR, Lanzavecchia A, Plebani A, Jayakar S, Ugazio AG. Ontogeny of secretory immunity: levels of secretory IgA and natural antibodies in saliva. Pediatr Res. 1980 Oct;14(10):1111–1114. [PubMed]
  • Rothkötter HJ, Pabst R. Lymphocyte subsets in jejunal and ileal Peyer's patches of normal and gnotobiotic minipigs. Immunology. 1989 May;67(1):103–108. [PMC free article] [PubMed]
  • Crabbé PA, Nash DR, Bazin H, Eyssen H, Heremans JF. Immunohistochemical observations on lymphoid tissues from conventional and germ-free mice. Lab Invest. 1970 May;22(5):448–457. [PubMed]
  • Bos NA, Meeuwsen CG, Wostmann BS, Pleasants JR, Benner R. The influence of exogenous antigenic stimulation on the specificity repertoire of background immunoglobulin-secreting cells of different isotypes. Cell Immunol. 1988 Apr 1;112(2):371–380. [PubMed]
  • Sudo N, Sawamura S, Tanaka K, Aiba Y, Kubo C, Koga Y. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J Immunol. 1997 Aug 15;159(4):1739–1745. [PubMed]
  • Mellander L, Carlsson B, Hanson LA. Appearance of secretory IgM and IgA antibodies to Escherichia coli in saliva during early infancy and childhood. J Pediatr. 1984 Apr;104(4):564–568. [PubMed]
  • Mellander L, Carlsson B, Jalil F, Söderström T, Hanson LA. Secretory IgA antibody response against Escherichia coli antigens in infants in relation to exposure. J Pediatr. 1985 Sep;107(3):430–433. [PubMed]
  • Lodinová-Zádníková R, Slavíková M, Tlaskalová-Hogenová H, Adlerberth I, Hanson LA, Wold A, Carlsson B, Svanborg C, Mellander L. The antibody response in breast-fed and non-breast-fed infants after artificial colonization of the intestine with Escherichia coli O83. Pediatr Res. 1991 Apr;29(4 Pt 1):396–399. [PubMed]
  • Long SS, Swenson RM. Development of anaerobic fecal flora in healthy newborn infants. J Pediatr. 1977 Aug;91(2):298–301. [PubMed]
  • Bennet R, Nord CE. Development of the faecal anaerobic microflora after caesarean section and treatment with antibiotics in newborn infants. Infection. 1987;15(5):332–336. [PubMed]
  • Eskew PN, Jr, Saywell RM, Jr, Zollinger TW, Erner BK, Oser TL. Trends in the frequency of cesarean delivery. A 21-year experience, 1970-1990. J Reprod Med. 1994 Oct;39(10):809–817. [PubMed]
  • Macfarlane A. At last--maternity statistics for England. BMJ. 1998 Feb 21;316(7131):566–567. [PMC free article] [PubMed]
  • Rook GA, Stanford JL. Give us this day our daily germs. Immunol Today. 1998 Mar;19(3):113–116. [PubMed]
  • Grönlund MM, Lehtonen OP, Eerola E, Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999 Jan;28(1):19–25. [PubMed]
  • Czerkinsky CC, Nilsson LA, Nygren H, Ouchterlony O, Tarkowski A. A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Dec 16;65(1-2):109–121. [PubMed]
  • Sedgwick JD, Holt PG. A solid-phase immunoenzymatic technique for the enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Feb 25;57(1-3):301–309. [PubMed]
  • Isolauri E, Virtanen E, Jalonen T, Arvilommi H. Local immune response measured in blood lymphocytes reflects the clinical reactivity of children with cow's milk allergy. Pediatr Res. 1990 Dec;28(6):582–586. [PubMed]
  • Kantele A. Immune response to prolonged intestinal exposure to antigen. Scand J Immunol. 1991 Feb;33(2):225–229. [PubMed]
  • Isolauri E, Sütas Y, Mäkinen-Kiljunen S, Oja SS, Isosomppi R, Turjanmaa K. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. J Pediatr. 1995 Oct;127(4):550–557. [PubMed]
  • David TJ. Infant feeding causes all cases of asthma, eczema, and hay fever. Or does it? Arch Dis Child. 1998 Aug;79(2):97–98. [PMC free article] [PubMed]
  • Dannaeus A. Age-related antibody response to food antigens. Pediatr Allergy Immunol. 1993;4(3 Suppl):21–24. [PubMed]
  • Holt PG. Immunoprophylaxis of atopy: light at the end of the tunnel? Immunol Today. 1994 Oct;15(10):484–489. [PubMed]
  • Simon GL, Gorbach SL. Intestinal flora in health and disease. Gastroenterology. 1984 Jan;86(1):174–193. [PubMed]
  • Kleessen B, Bunke H, Tovar K, Noack J, Sawatzki G. Influence of two infant formulas and human milk on the development of the faecal flora in newborn infants. Acta Paediatr. 1995 Dec;84(12):1347–1356. [PubMed]
  • Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics. 1983 Sep;72(3):317–321. [PubMed]
  • Bengmark S. Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut. 1998 Jan;42(1):2–7. [PMC free article] [PubMed]
  • Elhag KM, Senthilselvan A. A serogrouping scheme for the study of the epidemiology of Bacteroides fragilis. J Med Microbiol. 1988 Nov;27(3):199–205. [PubMed]
  • Moreau MC, Ducluzeau R, Guy-Grand D, Muller MC. Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin. Infect Immun. 1978 Aug;21(2):532–539. [PMC free article] [PubMed]
  • Pulverer G, Ko HL, Roszkowski W, Beuth J, Yassin A, Jeljaszewicz J. Digestive tract microflora liberates low molecular weight peptides with immunotriggering activity. Zentralbl Bakteriol. 1990 Mar;272(3):318–327. [PubMed]
  • Dahlgren UI, Wold AE, Hanson LA, Midtvedt T. Expression of a dietary protein in E. coli renders it strongly antigenic to gut lymphoid tissue. Immunology. 1991 Aug;73(4):394–397. [PMC free article] [PubMed]
  • Kramer DR, Cebra JJ. Early appearance of "natural" mucosal IgA responses and germinal centers in suckling mice developing in the absence of maternal antibodies. J Immunol. 1995 Mar 1;154(5):2051–2062. [PubMed]
  • Kantele JM, Kantele A, Arvilommi H. Circulating immunoglobulin-secreting cells are heterogeneous in their expression of maturation markers and homing receptors. Clin Exp Immunol. 1996 Jun;104(3):525–530. [PMC free article] [PubMed]
  • Forrest BD. Identification of an intestinal immune response using peripheral blood lymphocytes. Lancet. 1988 Jan 16;1(8577):81–83. [PubMed]
  • Kantele AM, Takanen R, Arvilommi H. Immune response to acute diarrhea seen as circulating antibody-secreting cells. J Infect Dis. 1988 Nov;158(5):1011–1016. [PubMed]
  • Kutteh WH, Koopman WJ, Conley ME, Egan ML, Mestecky J. Production of predominantly polymeric IgA by human peripheral blood lymphocytes stimulated in vitro with mitogens. J Exp Med. 1980 Nov 1;152(5):1424–1429. [PMC free article] [PubMed]
  • van der Heijden PJ, Stok W, Bianchi AT. Contribution of immunoglobulin-secreting cells in the murine small intestine to the total 'background' immunoglobulin production. Immunology. 1987 Dec;62(4):551–555. [PMC free article] [PubMed]
  • Van der Heijden PJ, Bianchi AT, Stok W, Bokhout BA. Background (spontaneous) immunoglobulin production in the murine small intestine as a function of age. Immunology. 1988 Oct;65(2):243–248. [PMC free article] [PubMed]
  • Neut C, Bezirtzoglou E, Romond C, Beerens H, Delcroix M, Noel AM. Bacterial colonization of the large intestine in newborns delivered by cesarean section. Zentralbl Bakteriol Mikrobiol Hyg A. 1987 Oct;266(3-4):330–337. [PubMed]
  • Shaheen SO, Aaby P, Hall AJ, Barker DJ, Heyes CB, Shiell AW, Goudiaby A. Measles and atopy in Guinea-Bissau. Lancet. 1996 Jun 29;347(9018):1792–1796. [PubMed]
  • Matricardi PM, Rosmini F, Ferrigno L, Nisini R, Rapicetta M, Chionne P, Stroffolini T, Pasquini P, D'Amelio R. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ. 1997 Apr 5;314(7086):999–1003. [PMC free article] [PubMed]
  • Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science. 1997 Jan 3;275(5296):77–79. [PubMed]
  • Cookson WO, Moffatt MF. Asthma: an epidemic in the absence of infection? Science. 1997 Jan 3;275(5296):41–42. [PubMed]
  • Hogg C. T-helper polarization in atopic disease--how early does it occur? Clin Exp Allergy. 1997 Nov;27(11):1237–1239. [PubMed]
  • Brandtzaeg P. Molecular and cellular aspects of the secretory immunoglobulin system. APMIS. 1995 Jan;103(1):1–19. [PubMed]

Articles from Archives of Disease in Childhood. Fetal and Neonatal Edition are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...