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. 2024;43(4):352-358.
doi: 10.12938/bmfh.2023-093. Epub 2024 Jun 17.

Effect of multi-strain bifidobacteria supplementation on intestinal microbiota development in low birth weight neonates: a randomized controlled trial

Kenichi Takeshita  1   2 , Haruka Takei  1 , Saori Tanaka  1 , Haruka Hishiki  1 , Yuta Iijima  1   3 , Hitoshi Ogata  1   3 , Kensuke Fujishiro  1   3 , Takahiro Tominaga  1   3 , Yuki Konno  1   3 , Yukiko Iwase  1   3 , Mamiko Endo  1   3 , Naruhiko Ishiwada  4 , Yoshiteru Osone  1   3 , Ryo Takemura  5 , Hiromichi Hamada  1 , Naoki Shimojo  6
Affiliations

Effect of multi-strain bifidobacteria supplementation on intestinal microbiota development in low birth weight neonates: a randomized controlled trial

Kenichi Takeshita et al. Biosci Microbiota Food Health. 2024.

Abstract

Single-strain Bifidobacterium species are commonly used as probiotics with low birth weight neonates. However, the effectiveness and safety of multi-strain Bifidobacterium supplementation are not well known. Thirty-six neonates weighing less than 2,000 g (558-1,943 g) at birth and admitted to a neonatal intensive care unit were randomly assigned to receive a single strain or triple strains of Bifidobacterium with lactulose enterally for 4 weeks from birth. The relative abundances of Staphylococcus and Bifidobacterium in the fecal microbiota at weeks 1, 2, and 4 were investigated. Based on the study results, no significant difference was detected between the two groups in the abundance of Staphylococcus; however, the triple-strain group had significantly high abundances of Bifidobacterium at weeks 2 and 4. The fecal microbiota in the triple-strain group had significantly lower alpha diversity (Bifidobacterium-enriching) after week 4 and was different from that in the single-strain group, which showed a higher abundance of Clostridium. No severe adverse events occurred in either group during the study period. Although no significant difference was detected between single- and multi-strain bifidobacteria supplementation in the colonization of Staphylococcus in the fecal microbiota of the neonates, multi-strain bifidobacteria supplementation contributed toward early enrichment of the microbiota with bifidobacteria and suppression of other pathogenic bacteria, such as Clostridium spp.

Keywords: gut microbiota; low birth weight neonates; multi-strain bifidobacteria; probiotics.

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Conflict of interest statement

Morinaga Milk Industry Co., Ltd. was not the sponsor of this study but did supply the probiotic products free of cost for the trial.

Figures

Fig. 1.
Fig. 1.
Consolidated standards of reporting trials (CONSORT) flow diagram for the study.
Fig. 2.
Fig. 2.
Comparison of the relative abundance of Firmicutes/Staphylococcaceae/Staphylococcus (a) and Actinobacteria/Bifidobacteriaceae/Bifidobacterium (b) in feces in the single-strain (white box) and triple-strain (gray box) groups. Boxes indicate the interquartile range, lines indicate the median, upper and lower whiskers indicate the maximum and minimum, cross marks indicate the mean, and dots indicate the outliers. Significant differences are indicated by *p<0.05 and q (by false discovery rate using the Benjamini and Hochberg method) <0.1.
Fig. 3.
Fig. 3.
Comparison of the proportions of each Bifidobacterium species in total fecal bacteria of infants receiving a single strain (white boxes) and triple strains (gray boxes) of Bifidobacterium, as measured by quantitative polymerase chain reaction. The vertical axis of these graphs represents the ratio of the logarithm of the number of each species to the total amount of fecal bifidobacteria. Boxes indicate the interquartile range, lines indicate the median, upper and lower whiskers indicate the maximum and minimum, cross marks indicate the mean, and dots indicate the outliers. Significant differences are indicated by *p<0.05 and q (by false discovery rate using the Benjamini and Hochberg method) <0.1.
Fig. 4.
Fig. 4.
Comparison of alpha and beta diversity of the gut microbiota. (a) Comparison of alpha diversity and coverage (mean ± SE) between the single-strain (white bar) and triple-strain (gray bar) groups as measured by the Shannon diversity index, faith_PD, observed_OTUs, and Chao1 index. Significant differences are indicated by *p<0.05. (b) Comparison of beta diversity between the study groups at week 4 depicted by principal coordinate analysis (PCoA) plots and 95% confidence ellipses based on Bray–Curtis and Jaccard dissimilarity. SE: standard error.
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