Efficacy of 1-Kestose Supplementation in Patients with Pancreatic Ductal Adenocarcinoma: A Randomized Controlled Pilot Study

Abstract

Less than half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) respond to chemotherapy, and the prognosis of PDAC is poor, which may be mediated by the gut microbiota. We investigated the clinical improvement effects of 1-kestose, a fructooligosaccharide, on PDAC chemotherapy in this single-center, randomized, controlled pilot trial conducted at Fujita Health University Hospital, which enrolled patients with PDAC. The trial included 1-kestose administration and non-administration groups. The 1-kestose group received 9 g of 1-kestose daily for 12 weeks, and their blood markers, imaging studies, physical findings, and gut microbiota were evaluated. In the 1-kestose administration group, the cancer marker CA19-9 significantly decreased, and there was a reduction in the neutrophil-to-lymphocyte ratio (NLR). There was also suppression of the reduction of albumin levels and of an increase in C-reactive protein. Additionally, Escherichia coli, which typically increases in PDAC, significantly decreased in the 1-kestose group. Thus, 1-kestose altered the gut microbiota and improved the prognostic factors for PDAC. Large-scale, long-term trials of 1-kestose interventions for PDAC are thus warranted to improve the prognosis of PDAC.

Keywords: 1-kestose; NLR; albumin; microbiota; pancreatic cancer.

Figure 1

Flowchart of the study protocol for patient selection. −KES, group not administered 1-kestose; +KES, group administered 1-kestose.

Figure 2

Analysis of the endpoints. Data are presented as the mean ± SD. (A) Change in albumin (Alb), (B) change in BMI, (C) change in extracellular water–total body water ratio, and (D) change in PhA from baseline to week 12. The Wilcoxon test was used for calculating statistical significance. −KES, group not administered 1-kestose; +KES, group administered 1-kestose.

Figure 3

Analysis of the endpoints. Data are presented as the mean ± SD. (A) Neutrophil count (%), (B) lymphocyte count (%), and (C) neutrophil to lymphocyte ratio (NLR) at week 12. The Mann–Whitney U test was used to calculate statistical significance. (D) Change in C-reactive protein (CRP), and (E) change in CA19-9 from baseline to week 12. The Wilcoxon test was used for calculating statistical significance. −KES, group not administered 1-kestose; +KES, group administered 1-kestose.

Figure 4

Analysis of the gut microbiota. Data are presented as the mean ± SD. (A,B) Comparing the observed Chao1 and Shannon indices as measures of the alpha diversity in the healthy and PDAC groups. The Wilcoxon test was utilized to calculate statistical significance. (C) The differential beta diversity of the gut microbiota was examined in Generalized UniFrac. Multivariate analysis of variance with permutational multivariate analysis of variance, p = 0.001.

Figure 5

Analysis of the gut microbiota. Data are presented as the mean ± SD. (A,B) Comparing the observed Chao1 and Shannon indices as measures of the alpha diversity from baseline to week 12 in the −KES and +KES groups. The Wilcoxon test was utilized to calculate statistical significance. (C) The differential beta diversity of the gut microbiota was examined in Generalized UniFrac. Multivariate analysis using permutational multivariate analysis of variance showed a significant difference between −KES/before and +KES/after at p = 0.001 but not between the other groups. −KES, group not administered 1-kestose; +KES, group administered 1-kestose.