The prebiotic effect of 1-kestose in low-birth-weight neonates taking bifidobacteria: a pilot randomized trial in comparison with lactulose

Abstract

Probiotics such as bifidobacteria have been given to low-birth-weight neonates (LBWNs) at risk for a disrupted gut microbiota leading to the development of serious diseases such necrotizing enterocolitis. Recently prebiotics such as lactulose are used together with bifidobacteria as synbiotics. However, faster and more powerful bifidobacteria growth is desired for better LBWN outcomes. The prebiotic 1-kestose has a higher selective growth-promoting effect on bifidobacteria and lactic acid bacteria in vitro among several oligosaccharides. Twenty-six premature neonates (less than 2,000 g) admitted to a neonatal intensive care unit (NICU) were randomly assigned to receive Bifidobacterium breve M16-V with either 1-kestose or lactulose once a day for four weeks from birth. A 16S rRNA gene analysis revealed similar increases in alpha-diversity from 7 to 28 days in both groups. The most dominant genus on both days was Bifidobacterium in both groups, with no significant difference between the two groups. Quantitative PCR analysis revealed that the number of Staphylococcus aureus tended to be lower in the 1-kestose group than in the lactulose group at 28 days. The number of Escherichia coli was higher in the 1-kestose group at 7 days. The copy number of total bacteria in the 1-kestose group was significantly higher than that in the lactulose group at 3 time points, 7, 14, and 28 days. No severe adverse events occurred in either group during the study period. l-Ketose may offer an alternative option to lactulose as a prebiotic to promote the development of gut microbiota in LBWNs.

Keywords: 1-kestose; Staphylococcus aureus; bifidobacteria; gut microbiota; lactulose; low birth weight neonates.

Fig. 1.

Flow diagram.

Fig. 2.

Alpha-diversity index of gut microbiota in each group. (a) Shannon alpha-diversity index, (b) Simpson alpha-diversity index.

Fig. 3.

Relative abundance ratios of gut microbiota at the genus level for each neonate at 7 days (3a), and at 28 days (3b). The relative abundance ratios of each neonates in the lactulose group (L-) were shown in the left side of this figure and those in the 1-kestose group (K-) were shown in the right side of this figure.

Fig. 4.

Bacterial counts of representative species at 7 and 28 days detected by RT-PCR of 16S rDNA from genomic DNA extracted from fecal samples. (a) Bifidobacterium spp., (b) Bifidobacterium longum, (c) Bifidobacterium breve, (d) Staphylococcus spp., (e) Staphylococcus aureus, (f) Escherichia coli, (g) Klebsiella pneumoniae. (h) All Bacteria. Median ± interquartile range and complete range, *p<0.05, ^♯p<0.1.