Lactulose Ingestion Induces a Rapid Increase in Genus Bifidobacterium in Healthy Japanese: A Randomised, Double-Blind, Placebo-Controlled Crossover Trial.

Oral administration of a low dose of lactulose increases the abundance of genus Bifidobacterium in the large intestine; however, the details of the daily variation in Bifidobacterium have not been researched. To observe how the intestinal microbiota, including Bifidobacterium, change, especially immediately after the initiation of ingestion, we conducted a randomised, placebo-controlled, double-blind crossover study of ingestion of 4 g lactulose/day for 2 weeks in 36 healthy Japanese (including males and females). The primary outcome was the percentage of Bifidobacterium in the faecal bacteria. In the lactulose-treatment group, the percentage of Bifidobacterium was already significantly higher 2 days after starting lactulose ingestion than in the placebo group (20.5 ± 1.2% vs. 17.1 ± 1.2%, p = 0.021). Significant differences were maintained, gradually widening, until the end of the 2-week intervention period. There were significant increases in the percentage and the number of Bifidobacterium with ingestion of 4 g lactulose/day for 2 weeks, but no significant changes in the beta diversity of the intestinal microbiota between lactulose and placebo ingestion. The percentage of Bifidobacterium in the faecal bacteria returned to its original level within a week of the end of intervention with lactulose.

Lactulose ingestion causes an increase in the abundance of gut-resident bifidobacteria in Japanese women: a randomised, double-blind, placebo-controlled crossover trial.

The genus Bifidobacterium comprises various bacterial species, and the complement of species within the human intestinal tract differs from individual to individual. The balance of these bifidobacterial species remains poorly understood, although it is known that the abundance of bifidobacteria increases following the ingestion of prebiotics. We previously conducted a randomised, placebo-controlled, double-blind, crossover study of 2 g/day lactulose ingestion for 2 weeks in 60 Japanese women. To study the effect of lactulose ingestion on each bifidobacterial species, here, we measured the abundance of each of the principal bifidobacterial species. After lactulose ingestion, the log cell counts of the Bifidobacterium adolescentis group (8.97±0.08 vs 9.39±0.08, P=0.0019), Bifidobacterium catenulatum group (9.45±0.10 vs 9.65±0.10, P=0.0032) and Bifidobacterium longum group (9.01±0.07 vs 9.29±0.07, P=0.0012) were significantly higher than in the placebo ingestion control group. However, the log cell counts were similar for Bifidobacterium breve (8.12±0.12 vs 8.33±0.12, P=0.20), Bifidobacterium bifidum (9.08±0.12 vs 9.42±0.14, P=0.095) and Bifidobacterium animalis subspecies lactis (8.65±0.53 vs 8.46±0.46, P=0.77). Cluster analysis of the log cell count data at the bifidobacterial species level revealed three distinct clusters, but the combinations and ratios of the constituent bifidobacteria were not affected by lactulose ingestion. Furthermore, principal coordinate analysis of the intestinal microbiota in the lactulose and placebo ingestion groups using Illumina MiSeq showed no significant differences in the intestinal microbiota as a whole. These results suggest that 2 g/day lactulose ingestion for 2 weeks significantly increases the abundance of intestinal bifidobacteria, but does not affect the intestinal microbiota as a whole.

Prebiotic effect of two grams of lactulose in healthy Japanese women: a randomised, double-blind, placebo-controlled crossover trial.

Sixty healthy Japanese women with a defaecation frequency of 2-4 times/week participated in this randomised, double-blind crossover trial. Participants received 2 g/day lactulose for 2 weeks and placebo in a random order, separated by a washout period of 3 weeks. Eight participants were excluded who did not satisfy the conditions, and therefore data from 52 were analysed. The primary outcome was defaecation frequency and the secondary outcomes were the number of defaecation days, faecal consistency, faecal volume, and the number and percentage of Bifidobacterium in faeces. The defaecation frequency (times/week) was significantly higher during lactulose (4.28±0.23) than placebo (3.83±0.23) treatment (delta (Δ) 0.45 [95% confidence interval (CI) 0.10-0.80], P=0.013). The defaecation days (days/week) was significantly higher during lactulose (3.77±0.17) than placebo (3.47±0.17) treatment (Δ0.30 [95% CI 0.04-0.56], P=0.024). Faecal consistency using the Bristol Stool Scale (/defaecation) was significantly higher during lactulose (3.84±0.10) than placebo (3.68±0.10) treatment (Δ0.16 [95% CI 0.00-0.31], P=0.044). Faecal volume (/week) was significantly higher during lactulose (21.73±3.07) than placebo (17.65±3.07) treatment (Δ4.08 [95% CI 0.57-7.60], P=0.024). The number of Bifidobacterium in faeces (log colony forming units/g faeces) was significantly higher during lactulose (9.53±0.06) than placebo (9.16±0.06) treatment (Δ0.37 [95% CI 0.23-0.49], P<0.0001). The percentage of Bifidobacterium in faeces was also significantly higher during lactulose (25.3±1.4) than placebo (18.2±1.4) treatment (Δ7.1 [95% CI 2.9-11.4], P=0.0014). Finally, straining at defaecation (/defaecation) during lactulose (3.62±0.24) treatment was significantly lower than during placebo (3.97±0.24) treatment (Δ0.35 [95% CI -0.69 - -0.02], P=0.037). No significant difference was observed between lactulose and placebo with regard to flatulence. Severe adverse effects did not occur. Thus, oral ingestion of 2 g/day lactulose had a prebiotic effect, increasing the number and percentage of bifidobacteria in faeces, softening the faeces, and increasing defaecation frequency, but without increasing flatulence.

A study of the prebiotic effect of lactulose at low dosages in healthy Japanese women.

To investigate the prebiotic effect of lactulose at low dosages, we assessed changes in defaecation frequency following ingestion of 1, 2, or 3 g/day of lactulose for 2 weeks. Each test was carried out after a 2-week washout period. This was an open-label, before-after trial that enrolled 26 healthy Japanese women. The defaecation frequency, number of defaecation days, and number of faecal bifidobacteria increased significantly compared with before ingestion of 1, 2, and 3 g/day of lactulose. These results suggest that even 1 g/day of lactulose could have a prebiotic effect.