Gut Microbiota Composition in Relation to the Metabolism of Oral Administrated Resveratrol

Abstract

Resveratrol (RSV) has been confirmed to confer multiple health benefits, and the majority of RSV tends to be metabolized in the gut microbiota after oral administration. In this study, the metabolism of RSV was investigated by using mouse models with distinct gut microbiota compositions: germ-free mice colonized with probiotics, conventional mouse, and DSS-induced colitis mouse models. The results demonstrated that in feces, the metabolites of RSV, including resveratrol sulfate (RES-sulfate), resveratrol glucuronide (RES-glucuronide), and dihydroresveratrol, significantly increased after probiotics colonized in germ-free mice. Furthermore, RES-sulfate and RES-glucuronide were below the detectable limit in the feces of conventional mice, with dihydroresveratrol being the dominant metabolite. Compared to the conventional mice, the ratio of Firmicutes/Bacteroides and the abundance of Lactobacillus genera were found significantly elevated in colitis mice after long-term ingestion of RSV, which shifted the metabolism of RSV in return. Our study provided critical implications in further application of RSV in foods and food supplements.

Keywords: Ligilactobacillus salivarious Li01; gut microbiota; metabolites; mouse model; resveratrol (RSV).

Figure 1

The structures of resveratrol and related metabolites including dihydroresveratrol, resveratrol-3-O-sulfate, resveratrol-3-glucuronide.

Figure 2

Gut microbiota composition in different mouse models. (a) Flow chart of animal studies in germ-free mice, conventional, and DSS-induced colitis mice. (b) Impact of RSV on colonized Li01 in germ-free mice. (c) Beta diversity evaluated by principal coordinates analysis (PCoA) of weighted unifrac distance. PCoA1 and PCoA2 represent the top two principal coordinates that captured most of the diversity. The fraction of diversity captured by the coordinate is given as a percentage. Groups were compared using analysis of similarities (ANOSIM) method. (d) Gut microbiota composition in healthy mice and DSS-induced colitis mice (before and after RSV intervention) analyzed by 16S rRNA gene sequencing analysis. Data are presented as mean ± SD. Significant difference was represented by * p  <  0.05, and analyzed by a one-way ANOVA with LSD’s post hoc test.

Figure 3

Quantification of RSV and its metabolites in feces (a), urine (b), serum, and tissues (c) in germ-free mice with/without Li01 colonization. Data are presented as mean ± SEM (n = 5). Significant difference was represented by * p  <  0.05, ** p  <  0.01, **** p  <  0.0001, and analyzed by either independent-samples t-test or nonparametric test (Mann–Whitney U-test).

Figure 4

RSV metabolism and distribution in conventional mice and DSS-induced colitis mice after oral administration. RSV and its metabolites were quantified in feces (a), urine (b), serum, and tissues (c) of both conventional mice and DSS-induced mice. 14 d and 29 d present different duration of RSV intervention. Data are presented as mean ± SEM (n = 5). Significant difference was represented by * p  <  0.05, ** p  <  0.01, and analyzed by independent-samples t-test and one-way ANOVA with LSD’s post hoc test or nonparametric test (Mann–Whitney U-test and Kruskal–Wallis H test).