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. 2018 Sep 21:11:1557-1571.
doi: 10.2147/IDR.S166348. eCollection 2018.

Effects of oral probiotic supplementation on gut Lactobacillus and Bifidobacterium populations and the clinical status of low-birth-weight preterm neonates: a multicenter randomized, double-blind, placebo-controlled trial

Magdalena Strus  1 , Ewa Helwich  2 , Ryszard Lauterbach  3 , Beata Rzepecka-Węglarz  4 , Katarzyna Nowicka  2 , Maria Wilińska  5 , Jerzy Szczapa  6 , Małgorzata Rudnicka  7 , Helena Sławska  8 , Marek Szczepański  9 , Aneta Waśko  10 , Aleksandra Mikołajczyk-Cichońska  10 , Anna Tomusiak-Plebanek  1 , Piotr B Heczko  1
Affiliations

Effects of oral probiotic supplementation on gut Lactobacillus and Bifidobacterium populations and the clinical status of low-birth-weight preterm neonates: a multicenter randomized, double-blind, placebo-controlled trial

Magdalena Strus et al. Infect Drug Resist. .

Abstract

Aim: Probiotic bacteria administered directly after birth to preterm neonates may improve gastrointestinal function and may reduce the incidence of late-onset sepsis, which is a frequent complication in this group.

Purpose: The main objective of this study was to evaluate whether a new probiotic bacterial mixture of Lactobacillus rhamnosus KL53A and Bifidobacterium breve PB04 given to preterm, low-birth-weight neonates would influence composition of their gut microbiota and sepsis rates.

Patients and methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial conducted in clinical centers of neonatal care in Poland. A probiotic or placebo preparation was given twice daily to 181 preterm low-birth-weight neonates who were eligible for enteral feeding between July 2012 and July 2013. The probiotic was given to 90 neonates, while placebo was given to 91 neonates. The gut microbiota was monitored by microbiological analysis of stool samples. Sepsis episodes were detected on the basis of clinical and laboratory findings and confirmed by blood cultures.

Results: Tested probiotic administration resulted in continuous increase of the Lactobacillus and Bifidobacterium counts in the gut microbiota. The applied tested strains successfully colonized the neonates gut since they were present in over 90% of stool samples, which was confirmed by molecular analysis. Regardless of the study group (probiotic or placebo), B. breve colonization correlated with lower staphylococcal sepsis incidence, which was irrespective of whether probiotics were given. No sepsis case caused by strains included in study probiotic was recorded.

Conclusion: Appropriately selected and characterized probiotic bacteria may be safely given to preterm neonates to normalize their distorted gut microbiota and may contribute to lower staphylococcal sepsis rates.

Keywords: Bifidobacterium; LBW neonates; Lactobacillus; gut microbiota; probiotics; staphylococcal sepsis.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Participant flow chart. Notes: *According to the protocol, participant could have been withdrawn from the trail due to more than one reason.
Figure 2
Figure 2
Lactobacillus count found in subsequent samplings in the probiotic group (green) and placebo group (red), transformed into logarithms. Notes: The chart shows median values, quartile intervals, range, and outliers determined using American Analyst Society methods. **p<0.01; ***p<0.001.
Figure 3
Figure 3
Bifidobacterium count found in subsequent samplings in the probiotic group (green) and placebo group (red), transformed into logarithms. Notes: The chart shows median values, quartile intervals, range, and outliers determined using American Analyst Society methods. *p<0.05; ***p<0.001.
Figure 4
Figure 4
Percentage participation of L. rhamnosus and B. breve in the total cultivable part of the fecal microbiota of neonates from probiotic (green) group versus placebo (red) group. Notes: The chart shows median values, quartile intervals, range, and outliers determined using American Analyst Society methods. *p<0.05; **p<0.01; ***p<0.001; ~ Means around the significance threshold 0.0750>p>0.05. Abbreviations: L. rhamnosus, Lactobacillus rhamnosus; B. breve, Bifidobacterium breve.
Figure 5
Figure 5
Percentage of neonates colonized by L. rhamnosus KL53A and B. breve PB04 strains (PP population, probiotic group, n = 80). Abbreviations: L. rhamnosus, Lactobacillus rhamnosus; B. breve, Bifidobacterium breve; PP, perprotocol.
Figure 6
Figure 6
Percentage of participants colonized with bacteria representing normal gut microbiota compared with those colonized with potentially pathogenic bacteria or with both types of microbes or no bacteria or fungi during the course of the study. (A) Probiotic group; (B) placebo group. Notes: LA – normal microbiota: Lactobacillus and Bifidobacterium (blue). PB – potentially pathogenic bacteria and fungi: Clostridium spp., Escherichia coli, Candida albicans, Klebsiella spp., Enterobacter spp., Staphylococcus aureus including MRSA, and Staphylococcus epidermidis including MRSE (red). MF – mixed flora (green). No flora – no bacteria or fungi present (yellow). Abbreviations: MRSE, methicillin-resistant S. epidermidis; MRSA, methicillin-resistant S. aureus..
Figure 7
Figure 7
Correlation between B. breve gut numbers and staphylococcal sepsis (Observed in both groups). Abbreviations: B. breve, Bifidobacterium breve.
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