Fermented Gold Kiwi Improves Gastrointestinal Motility and Functional Constipation: An Animal Study and Human Randomized Clinical Test

Abstract

Constipation is a functional disorder of the gastrointestinal system characterized by difficult bowel movements, infrequent defecation, reduced water content, and hard stools. This study aims to evaluate the preventive effects of fermented gold kiwis (FGK) on loperamide-induced constipation in rats and investigate its efficacy in improving constipation symptoms in human patients through a randomized clinical trial. In the animal study, FGK was administered orally at doses of 50, 125, and 250 mg/kg to constipated rats for two weeks, resulting in significant improvements in constipation parameters. FGK increased serum serotonin and acetylcholine levels and suppressed increases in serum dopamine concentration. FGK also upregulated mRNA expression of the serotonin-synthesizing receptors 5-HT3R and 5-HT4R and suppressed the expression of the dopamine 2-receptor (D2R) in the duodenum. Furthermore, FGK inhibited inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In the clinical trials, the improvement in constipation symptoms was evaluated using the gastrointestinal symptom rating scale (GSRS). Clinical trial participants reported significant improvements in constipation symptoms after receiving FGK. These findings suggest that FGK effectively relieves constipation in both animals and humans, indicating its potential as an effective dietary supplement.

Keywords: constipation; fermented gold kiwi; loperamide; neurotransmitter; probiotics.

Figure 1

Flowchart of the fermentation process of gold kiwi.

Figure 2

Loperamide-induced constipation in rats: experimental design.

Figure 3

Effects of FGK on gastrointestinal motility in SD rats. (A) Gastric emptying in cisplatin-induced SD rats; (B) geometric center in atropine-induced SD rats; (C) pepsin activity; (D) gastric juice volume; (E) gastric juice pH; (F) titratable acidity; (G) total acidity. Data are presented as the mean ± SEM (n = 6). ^a–d Different letters indicate significant differences between groups at the p < 0.05 levels. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine the specific differences between groups.

Figure 3

Effects of FGK on gastrointestinal motility in SD rats. (A) Gastric emptying in cisplatin-induced SD rats; (B) geometric center in atropine-induced SD rats; (C) pepsin activity; (D) gastric juice volume; (E) gastric juice pH; (F) titratable acidity; (G) total acidity. Data are presented as the mean ± SEM (n = 6). ^a–d Different letters indicate significant differences between groups at the p < 0.05 levels. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine the specific differences between groups.

Figure 4

Change in fecal parameters in loperamide-induced constipation rats. (A) Number of feces during the experimental period after injecting loperamide; (B) representative pictures of the colons of rats in each group; (C) number of feces in the colon, as counted, with symbols representing individuals rat fecal counts; (D) number of feces in the cages, as counted in the final day; (E) fecal water content on the final day, with symbols indicating individual rat measurements. Data are presented as mean ± SEM (n = 6). ^a,b Different letters indicate significant differences between groups at the p < 0.05 level. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine specific differences between the groups.

Figure 5

Effects of (A) 5-HT3R, (B) 5-HT4R, and (C) D2R mRNA expression in the duodenum. All data were calculated using the ∆∆Ct method of quantitative RT-PCR, and transcript expression was normalized using the GAPDH housekeeping gene. Data are presented as the mean ± SEM (n = 6). ^a–c Different letters indicate significant differences between groups at the p < 0.05 level. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine specific differences between the groups.

Figure 6

Effects of FGK on the serum neurotransmitter in loperamide-induced constipation rats: (A) serotonin; (B) dopamine; (C) acetylcholine. Data are presented as the mean ± SEM (n = 6). ^a–d Different letters indicate significant differences between groups at the p < 0.05 level. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine specific differences between the groups.

Figure 7

Effects of FGK on mRNA expression of inflammatory cytokines in loperamide-induced constipation rats. (A) TNF-α; (B) IL-1β; (C) IL-6. Data are presented as the mean ± SEM (n = 6). ^a–c Different letters indicate significant differences between groups at the p < 0.05 level. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine specific differences between the groups.

Figure 8

Effects of FGK on the mRNA expression of fecal bacteria groups in loperamide-induced constipation rats. Data are presented as the mean ± SEM (n = 6). ^a–c Different letters indicate significant differences between groups at the p < 0.05 level. Statistical analysis was performed using a one-way ANOVA, followed by Tukey’s post hoc test to determine specific differences between the groups.

Figure 9

Randomized human clinical study participant disposition.

Figure 10

Changes in the GSRS lower gastrointestinal part before (baseline) and after (8 weeks) administration of FGK. (A) GSRS lower gastrointestinal part score at visit 2 (baseline); (B) GSRS lower gastrointestinal part score at visit 5 (8 weeks); (C) the change from visit 2 to visit 5. Data are expressed as the mean ± SD. (A) Comparisons between the groups using the p-values from two-sample t-tests. (B) Comparisons between the groups using Wilcoxon signed-rank tests. *^,** Comparisons within the groups using paired t-tests. *** 95% two-sided confidence interval for differences in the least squares mean.

Figure 11

Changes in GSRS constipation symptoms before (baseline) and after (8 weeks) administration of FGK. (A) GSRS constipation symptom score at visit 2 (baseline); (B) GSRS constipation symptom score at visit 5 (8 weeks); (C) the change from visit 2 to visit 5. Data are expressed as the mean ± SD. (A) Comparisons between the groups using the p-values from two-sample t-tests. (B) Comparisons between the groups using Wilcoxon signed-rank tests. *^,** Comparisons within the groups using paired t-tests. *** 95% two-sided confidence interval for differences in the least squares mean.

Figure 12

Changes in the GSRS sensation of not completely emptying the bowels before (baseline) and after (8 weeks) administration of FGK. (A) The sensation of not completely emptying the bowels score at visit 2 (baseline); (B) the sensation of not completely emptying the bowels score at visit 5 (8 weeks); (C) the change from visit 2 to visit 5. Data are expressed as the mean ± SD. (A) Comparisons between the groups using the p-values from two-sample t-tests. (B) Comparisons between the groups using Wilcoxon signed-rank tests. *^,** Comparisons within the groups using paired t-tests. *** 95% two-sided confidence interval for differences in the least squares mean.