Published online July 1, 2005
PEDIATRICS Vol. 116 No. 1 July 2005, pp. 293 (doi:10.1542/peds.2005-0791)
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Probiotics and Necrotizing Enterocolitis

Hung-Chih Lin, MD
Bai-Horng Su, MD, PhD
Department of Pediatrics,
China Children's Hospital,
China Medical University,
Taichung 404, Taiwan

Chang-Hai Tsai, MD, PhD
Taichung Healthcare and Management University,
Taichung 413, Taiwan

In Reply.

We appreciate Dr Mack's critique and query. Yes, different probiotics strains do have different effects1,2; it is difficult to choose a suitable strain of Lactobacillus and Bifidobacterium to fit the study purpose. The anaerobic lactic acid bacteria (Lactobacillus and Bifidobacterium) are the predominant organisms in healthy breastfeeding infants. They not only do not undergo translocation but also have a protective role against the translocation of other bacteria by acid-fermentation processes and the production of antimicrobial bacteriocins.

We knew that the distributing company mentioned in our study (Swiss Serum and Vaccine Institute, Berne, Switzerland) had been bought by another company only after we had completed the study. The new company did in fact change Bifidobacterium infantis to Bifidobacterium bifidum. Lactobacillus acidophilus (1004356, obtained from the American Type Culture Collection in 1973) and B infantis (1015697, also obtained from the American Type Culture Collection in 1973) were the specific strains used in our study.

We are aware that some reports have shown that probiotic effects are dose dependent. However, the dose dependence is controversial, and most of the studies were in vitro experiments.3–6 The usual effective dosage in humans is 107 to 109 colony forming units (CFU)/mg per day. We stated that the dose was 125 mg/kg, given twice daily, instead of stating 4 x 106 CFU/mg to make it easier for the nursing staff on the breast milk team to administer the correct dosage. Infloran (250 mg) contains 109 CFU of L acidophilus and B infantis, respectively, so the total dose used in our study was 125 x 2 x 4 x 106 CFU/mg = 109 CFU/mg per day.

We knew that our study was not perfect. However, we did it sincerely and followed sound clinical research methodology. There are several issues that need additional investigation; rigorously designed double-blind, controlled, clinical trials are vital to investigate the unresolved issues related to the dosage, initiation, and duration of use, the single or multistrain formulation of probiotics, and the concomitant use of prebiotics, probiotics, and synbiotics.

Although many researchers have revealed that Lactobacillus and Bifidobacterium colonized in the stool of preterm infants after oral probiotics,7,8 the mechanism of the beneficial effect of probiotics on necrotizing enterocolitis related to the change of the ecosystem in the intestine is yet to be shown. Cytokine changes in the intestinal mucosa may also be responsible for the beneficial effect of oral probiotics. We hope that our multicenter collaborative study of probiotics in Taiwan will answer these questions in the future.

REFERENCES

  1. Ibnou-Zekri N, Blum S, Schiffrin EJ, von der Weid T. Divergent patterns of colonization and immune response elicited from two intestinal Lactobacillus strains that display similar properties in vitro. Infect Immun.2003; 71 :428 –436[Abstract/Free Full Text]
  2. Kimoto H, Mizumachi K, Okamoto T, Kurisaki J. New Lactococcus strain with immunomodulatory activity: enhancement of Th1-type immune response. Microbiol Immunol.2004; 48 :75 –82[Medline]
  3. Lammers KM, Helwig U, Swennen E, et al. Effect of probiotic strains on interleukin 8 production by HT29/19A cells. Am J Gastroenterol.2002; 97 :1182 –1186[CrossRef][ISI][Medline]
  4. Alvarez S, Herrero C, Bru E, Perdigon G. Effect of Lactobacillus casei and yogurt administration on prevention of Pseudomonas aeruginosa infection in young mice. J Food Prot.2001; 64 :1768 –1774[Medline]
  5. Gill HS, Rutherfurd KJ. Viability and dose-response studies on the effects of the immunoenhancing lactic acid bacterium Lactobacillus rhamnosus in mice. Br J Nutr.2001; 86 :285 –289[Medline]
  6. Reid G, Beuerman D, Heinemann C, Bruce AW. Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora. FEMS Immunol Med Microbiol.2001; 32 :37 –41[CrossRef][ISI][Medline]
  7. Kitajima H, Sumida Y, Tanaka R, Yuki N, Takayama H, Fujimura M. Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial. Arch Dis Child Fetal Neonatal Ed.1997; 76 :F101 –F107[Abstract/Free Full Text]
  8. Millar MR, Bacon C, Smith SL, Walker V, Hall MA. Enteral feeding of premature infants with Lactobacillus GG. Arch Dis Child.1993; 69 :483 –487[Abstract]
PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics




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