Prebiotic UG1601 mitigates constipation-related events in association with gut microbiota: A randomized placebo-controlled intervention study

Abstract

Background: Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids (SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin, lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking.

Aim: To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation.

Methods: Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined. The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated.

Results: There were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement. However, after prebiotic usage, serum cluster of differentiation (CD) 14 and lipopolysaccharide (LPS) concentrations were significantly decreased (CD14, P = 0.012; LPS, P < 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group (P < 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group (P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae (phylum Firmicutes, class Clostridia) (P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs (P < 0.05).

Conclusion: Alterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.

Keywords: Constipation; Endotoxemia; Gut microbiota; Prebiotics; Short-chain fatty acids.

Figure 1

CONSORT diagram illustrating participant recruitment, follow-up, and analysis.

Figure 2

Changes in the serum cluster of differentiation 14 and lipopolysaccharide concentrations after 4 wk of intervention. A and C: Changes in the serum cluster of differentiation (CD) 14 after 4 wk of intervention; B and D: Changes in the serum cluster of lipopolysaccharide (LPS) concentrations after 4 wk of intervention. After 4 wk of intervention, the concentrations of serum CD 14 and LPS were significantly reduced in the prebiotics group. Bar charts show the mean ± standard error of the mean. ^aP < 0.05; ^bP < 0.001. Significantly different from the values at placebo or baseline, using the Student’s t-test or paired t-test. CD: Cluster of differentiation; LPS: Lipopolysaccharide.

Figure 3

Analysis of Relative abundance. A: Relative abundance of acetate-producing bacteria; B: Propionate-producing bacteria; C: Butyrate-producing bacteria; D: Prebiotic-sensitive bacteria. In the prebiotics group, the relative abundance of Bifidobacterium adolescentis was decreased and that of Roseburia hominis was increased after 4 wk of intervention. Box plots show the 25th and 75th percentiles, median, and range. Outliers are expressed as a small circle. ^cP < 0.05. Significantly different from the values at baseline, using the Student’s t-test.

Figure 4

Microbial community analysis between responders and non-responders treated with prebiotics. A: Gut microbiome phylum profile of the responder and non-responder groups at baseline and week 4; B: Major microbiome phylum profile at week 4; C and D: Changes in the relative abundance of subordinate taxa (from baseline to week 4); E: Correlations of gut microbiota with serum endotoxemia markers and fecal short chain fatty acids. The abundances of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were reduced in the responders after 4 wk of intervention representing the inverse associations with several fecal short chain fatty acids. Box plots show the 25th and 75th percentiles, median, and range. Outliers are expressed as a small circle (C). ^eP < 0.05. Significantly different from the values at responders, using the Student’s t-test (D). The number in each box indicates coefficient of correlation. The blue color implies a positive correlation, while the red color indicates a negative correlation. Statistically significant correlation is highlighted with a red line (E). CD: Cluster of differentiation; LPS: Lipopolysaccharide; BMI: Body mass index.