Gut microbiota-mediated associations of green tea and catechin intakes with glucose metabolism in individuals without type 2 diabetes mellitus: a four-season observational study with mediation analysis

Abstract

This four-season observational study aimed to examine the mediating role of the gut microbiota in the associations between green tea and catechin intakes and glucose metabolism in individuals without type 2 diabetes mellitus (T2DM). In each of the 4 seasons, 85 individuals without T2DM (56 male [65.9%]; mean [standard deviation] age: 43.3 [9.4] years) provided blood samples, stool samples, 3-day weighed dietary records, and green tea samples. Catechin intake was estimated by analyzing the tea samples. Linear mixed-effects model analysis showed that green tea intake was negatively associated with fasting blood glucose and insulin levels, even after considering the seasonal variations. Of the gut microbial species associated with green tea intake, the mediation analysis revealed that Phocaeicola vulgatus mediated the association between green tea intake and fasting blood glucose levels. These findings indicate that green tea can improve glucose metabolism by decreasing the abundance of P. vulgatus that is associated with elevated blood glucose levels in individuals without T2DM.

Keywords: Catechin; Green tea; Gut microbiota; Mediation analysis; Season; Type 2 diabetes mellitus.

Fig. 1

Characteristics of the human gut microbiota at the phylum (a) and genus levels (b) in each of the four seasons. Each bar chart shows the relative abundance of 6 most abundant phyla and 20 most abundant genera. Other bacterial phyla and genera were combined as residue

Fig. 2

Heat map of the associations of green tea and catechin intakes with the relative abundances of the gut microbial species. Of the 71 species selected as shown in Table 3, only those significantly associated with green tea intake were plotted, with darker colors indicating smaller p values. Symbols represent significant positive (blue, +) and negative (red, −) associations, even after adjustment of p values for the false discovery rate (q < 0.20). Abbreviation: EGCG, epigallocatechin-3-gallate (color figure online)

Fig. 3

Mediation effect of Phocaeicola vulgatus in the association between the total effect of green tea intake and fasting blood glucose levels. a The total effect of green tea intake on fasting blood glucose levels (path c). b Mediation analysis was used to divide the total effect (path c in a) into the average direct effect of exposure (ADE, path ć) and the average causal mediating effect (ACME, path ab). Regression coefficients and its corresponding 95% confidence intervals for the association between green tea intake and the relative abundance of P. vulgatus (path a) and the association between the relative abundance of P. vulgatus and fasting blood glucose levels (path b) were estimated using the linear mixed-effects models. The relative abundance of P. vulgatus and fasting blood glucose levels was modeled as the continuous mediator and outcome, respectively. Green tea intake was categorized into low- and high-intake groups based on their median values (135 mL/1,000 kcal) to make a contrast in the mediation analysis (Imai et al. 2010). Abbreviations: CI, confidence interval; ACME, average causal mediation effect; ADE, average direct effect; Prop. Mediated (%), the proportion of ACME to total effect