Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Increase Bifidobacterium but Reduce Butyrate Producing Bacteria with Adverse Glycemic Metabolism in healthy young population

Abstract

The gut microbiota has been implicated in glucose intolerance and its progression towards type-2 diabetes mellitus (T2DM). Relevant randomized clinical trial with prebiotic intervention was inadequate. We sought to evaluate the impact of fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on glycemia during oral glucose tolerance test (OGTT) and intestinal microbiota. A randomized double-blind cross-over study was performed with 35 adults treated with FOS and GOS for 14 days (16 g/day). Faeces sampling, OGTT and anthropometric parameters were performed. Short-term intake of high-dose prebiotics had adverse effect on glucose metabolism, as in FOS intervention demonstrated by OGTT (P < 0.001), and in GOS intervention demonstrated by fasting glucose (P < 0.05). A significant increase in the relative abundance of Bifidobacterium was observed both in FOS and GOS group, while the butyrate-producing bacteria like Phascolarctobacterium in FOS group and Ruminococcus in GOS group were decreased. A random forest model using the initial microbiota was developed to predict OGTT levels after prebiotic intervention with relative success (R = 0.726). Our study alerted even though FOS and GOS increased Bifidobacterium, they might have adverse effect on glucose metabolism by reducing butyrate-producing microbes. Individualized prebiotics intervention based on gut microbiome needs to be evaluated in future.

Figure 1

Flow chart of subject recruitment, allocation and analysis.

Figure 2

Comparison of the glucose profiles with OGTT of subjects in (A) and (C) FOS Day0 and FOS Day14; (B) and (D) GOS Day0 and GOS Day14. Comparison of the butyric acid in feces. (E) FOS Day0 and Day 14; (F)GOS Day0 and Day 14. Data are means ± SD (*p < 0.05; Paired t tests).

Figure 3

(A–D) Comparison of α-diversity between the gut microbiota of FOS Day0 and FOS Day14, GOS Day0 and GOS Day14. Four indices were used to represent the α-diversity which is (A) Chao1, (B) observed species, (C) Shannon index, and (D) PD whole tree. PD indicates phylogenetic diversity. Data are mean ± 95% CI. (*P < 0.05; Paired t tests); (E,F) Principal coordinate analysis based on the unweighted UniFrac distances. (E) FOS intervention, (F) GOS intervention. The red dots represent samples (intestinal microbiota) of pre-intervention, and the blue dots represent samples of post-intervention.

Figure 4

Taxonomic summary of the gut microbiota of FOS Day0 and FOS Day14, GOS Day0 and GOS Day14 at (A) phylum level and (B) genus level. Significantly discriminative taxa between (C) FOS Day0 and FOS Day14, (D) GOS Day0 and GOS Day14 determined using linear discriminant analysis effect size (LDA effect size). The red bar chart represents the bacteria that was more abundant in patients’ fecal samples, and the blue bar chart represents the controls.

Figure 5

Variability of OGTT in two prebiotics intervention (A). Red dots represent OGTT elevated after both prebiotics. Green dots represent OGTT reduced after both prebiotics. Yellow dots represent OGTT reduced after FOS intervention, but elevated after GOS intervention; Blue dots represent OGTT reduced after GOS intervention, but elevated after FOS intervention; Glucose profiles changing with prebiotics intervention in Participants 104 and (B) Participants 204; (C) System clustering of microbiota composition at genus level. The names of several of the most abundant genera that included shown in the heatmap are listed on the right of the figure. The groups are listed at the top of the heatmap. FOS Day0, FOS Day14, GOS Day0 and GOS Day14 represent different prebiotic period. Different color represents samples from different subjects. And the color bar at the right of the heatmap shows the relative abundance of the sequences in each fecal sample.

Figure 6

Accurate predictions of personalized OGTT responses after prebiotics intervention. (A–C) OGTT predictions. Dots represent predicted (x axis) and measured OGTT (y axis) after prebiotic intervention, for a model based: (A) only on the initial OGTT (B) on the initial OGTT and microbiome; (C) only on the microbiome. (D) Unique bacterial taxa and host factor identified in OGTT with the model. The box size to the prediction OGTT indicate the importance of the factor attributed to the OGTT outcomes. The names of the important bacterial taxa are listed on the left of the figure; the important host factors are listed on the right of the figure.