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Efficacy of Different Probiotic Combinations on Death and Necrotizing Enterocolitis in a Premature Rat Model

Wu, Shu-Fen; Chiu, Hsiao-Yu*; Chen, An-Chyi; Lin, Hsiang-Yu*; Lin, Hung-Chih; Caplan, Michael§

Journal of Pediatric Gastroenterology and Nutrition: July 2013 - Volume 57 - Issue 1 - p 23–28
doi: 10.1097/MPG.0b013e3182929210
Original Articles: Gastroenterology

Objective: The aim of the present study was to investigate the most effective probiotic combinations to prevent death and necrotizing enterocolitis (NEC) in a premature rat model.

Methods: One hundred fifty-eight premature Sprague-Dawley premature rats were enrolled. Probiotic strains Bifidobacterium bifidum, B longum, Lactobacillus acidophilus, L plantarum, and B breve were fed as a single strain or mixture with 2 or 3 strains for a total of 9 study groups; control groups received no exogenous probiotic supplement. Fecal samples were collected for 72 hours to detect probiotic strains and pathologic strains by real-time polymerase chain reaction. Colony counts of probiotic strains Escherichia coli and Klebsiella were compared between groups before and after 36 hours of the study period. The incidence of death and NEC were compared via Fisher exact test between groups.

Results: The results demonstrated that L plantarum alone (P = 0.0026) and B bifidum with B longum together (P = 0.0017) were more effective in reducing NEC as compared with the control group. All of the study groups except B breve and B bifidum with B breve definitely prevented death compared with controls. B bifidum and B longum together had significantly lower mortality than the control group (P < 0.0001). Colony counts of E coli and Klebsiella in stool samples were significantly decreased in the B bifidum, B longum, and L plantarum group compared with the other study and control groups after 36 hours.

Conclusions: Administration of a mixture of probiotic strains with B bifidum and B longum was most effective in preventing death and NEC in this animal model, and these observations provide an evidence-based strategy for designing further neonatal clinical trials.

*Department of Pediatrics, China Medical University Hospital

School of Medicine, China Medical University

School of Chinese Medicine, China Medical University, Taichung, Taiwan

§Pritzker School of Medicine, University of Chicago, Chicago, IL.

Address correspondence and reprint requests to Hung-Chih Lin, MD, Department of Pediatrics, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung 404, Taiwan (e-mail:

Received 10 May, 2012

Accepted 16 January, 2013

Drs Wu and Chiu participated equally in this study.

This study was supported by the National Science Council of Taiwan (Grant NSC 95–2314-B-039–034) and China Medical University Hospital (grant DMR96–100).

The authors report no conflicts of interest.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,