Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial

Abstract

Constipation is a major issue for 10-20% of the global population. In a double-blind randomized placebo-controlled clinical trial, we aimed to determine a dose-response effect of galacto-oligosaccharides (GOS) on stool characteristics and fecal microbiota in 132 adults with self-reported constipation according to Rome IV criteria (including less than three bowel movements per week). Subjects (94% females, aged: 18-59 years) received either 11 g or 5.5 g of Biotis^TM GOS, or a control product, once daily for three weeks. Validated questionnaires were conducted weekly to study primarily stool frequency and secondary stool consistency. At base- and endline, stool samples were taken to study fecal microbiota. A trend towards an increased stool frequency was observed after the intervention with 11 g of GOS compared to control. While during screening everybody was considered constipated, not all subjects (n = 78) had less than three bowel movements per week at baseline. In total, 11 g of GOS increased stool frequency compared to control in subjects with a low stool frequency at baseline (≤3 bowel movements per week) and in self-reported constipated adults 35 years of age or older. A clear dose-response of GOS was seen on fecal Bifidobacterium, and 11 g of GOS significantly increased Anaerostipes hadrus. In conclusion, GOS seems to be a solution to benefit adults with a low stool frequency and middle-aged adults with self-reported constipation.

Keywords: constipation; galacto-oligosaccharides; microbiota; stool characteristics; stool consistency; stool frequency.

Figure 1

Flow diagram.

Figure 2

Stool frequency during the intervention period of ITT population, (A) Overview of the total ITT population for the ● control group (n = 43), ν 11 g GOS group (n = 44), and the 5.5 g GOS group (n = 45). Mixed model analysis showed a trend towards significance (p = 0.095) between the control and 11 g GOS groups at week 3. (B) Subjects from ITT population with a basal stool frequency ≤3, for the ● control group (n = 33), ν 11 g GOS group (n = 33), and the 5.5 g GOS group (n = 32). Mixed model analysis showed a significant difference * (p = 0.027) between the control and 11 g GOS groups at week 3. (C) Subjects from ITT population <35 years of age ● control group (n = 16), ν 11 g GOS group (n = 19), and the 5.5 g GOS group (n = 15). No significant differences were found in the subjects <35 years of age after mixed model analysis. (D) Subjects ≥35 years of age for the ● control group (n = 27), ν 11 g GOS group (n = 25), and the 5.5 g GOS group (n = 30). Mixed model analysis showed a significant difference * (p = 0.010) between the control and 11 g GOS groups in subjects ≥35 years of age at week 3.

Figure 3

(A) Constipation score (based on Agachan et al., 1997) (ranging from 0–30) and (B) symptom severity score (PAC-SYM) (ranging from 0–48) of ITT population at baseline and after the intervention period. The ANCOVA did not show any differences in Constipation Score between 11 g GOS and control (p = 0.529), nor between 5.5 g GOS and control (p = 0.717). The ANCOVA did not show any differences in PAC-SYM scores between 11 g GOS and control (p = 0.801), nor between 5.5 g GOS and control (p = 0.446).

Figure 4

Partial RDA of (A) 11 g GOS group in time and (B) 5.5 g GOS group in time. Red squares represent baseline samples, blue triangles represent endline samples. Envelopes are 2D-normal-based ellipses at the 66% level. Grey arrows represent the genera with the best fit in the ordination space on the horizontal axis.

Figure 5

Change in Bifidobacterium over time (2log ratio of relative abundance at endline (week 3) and at baseline) for the different study groups. Boxplots are displayed as Tukey whiskers.

Figure 6

Change in Anaerostipes over time (2log ratio of relative abundance at endline (week 3) and at baseline) for the different study groups. Boxplots are displayed as Tukey whiskers.