Influence of Intestinal Microbiota on the Catabolism of Flavonoids in Mice

Abstract

Although in vitro studies have shown that flavonoids are metabolized into phenolic acids by the gut microbiota, the biotransformation of flavonoids by intestinal microbiota is seldom studied in vivo. In this study, we investigated the impact of the gut microbiota on the biotransformation of 3 subclasses of flavonoids (flavonols, flavones, and flavanones). The ability of intestinal microbiota to convert flavonoids was confirmed with an in vitro fermentation model using mouse gut microflora. Simultaneously, purified flavonoids were administered to control and antibiotic-treated mice by gavage, and the metabolism of these flavonoids was evaluated. p-Hydroxyphenylacetic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, hydrocaffeic acid, coumaric acid, and 3-(4-hydroxyphenyl)propionic acid were detected in the serum samples from the control mice after flavonoid consumption. The serum flavonoid concentrations were similar in both groups, whereas the phenolic metabolite concentrations were lower in the antibiotic-treated mice than in the control mice. We detected markedly higher flavonoids excretion in the feces and urine of the antibiotic-treated mice compared to the controls. Moreover, phenolic metabolites were upregulated in the control mice. These results suggest that the intestinal microbiota are not necessary for the absorption of flavonoids, but are required for their transformation.

Protective Effect of Protocatechuic Acid on TNBS-Induced Colitis in Mice Is Associated with Modulation of the SphK/S1P Signaling Pathway

“…Moreover, it has been hypothesized that oxidative stress could enhance inflammation in IBD and colitis-associated colon cancer through impaired S1P degradation [2]. Protocatechuic acid (PCA, 3-4-dihydroxybenzoic acid) is a simple phenolic acid found in many edible vegetables, fruits and nuts [9], which has been identified as a major metabolite of complex polyphenols and considered the best biomarker of flavonoid consumption [10,11]. A number of cellular and animal studies have shown that PCA has multifaceted biological effects, including a potent antioxidant and anti-inflammatory activity, in different tissues [9].…”

Age-Related Variations in Intestinal Microflora of Free-Range and Caged Hens

“…The significant role of gastrointestinal (GI) microflora in digestion, absorption, health, productivity and other physiological functions has been well recognized (Pourabedin and Zhao, 2015), moreover the intestinal microflora may also protect hosts from pathogens (Waite and Taylor, 2014) and inflammatory bowel diseases to improve gut health (Giacomin et al, 2016); also Lin et al (2016) studied that intestinal microbiota were necessary for transformation of flavonoids to provide health benefits for the prevention and treatment of some types of chronic diseases. Therefore, it is very relevant to assay the composition of the GI microflora (Barbosa et al, 2016).…”

Cancer chemoprevention through dietary flavonoids: what’s limiting?

“…The colonic microflora also reduces cholesterol absorption and increases mucus secretion in the gut [162, 163]. The role of the colonic microflora on the absorption, metabolism, and bioavailability of flavonoids remains to be delineated [164]. It has been reported that unabsorbed flavonoids can be biotransformed to small phenolic compounds that have similar effects, but improved bioavailability, compared to the parent compound [165].…”

“…It has been reported that unabsorbed flavonoids can be biotransformed to small phenolic compounds that have similar effects, but improved bioavailability, compared to the parent compound [165]. In contrast, the colonic microflora can extensively metabolize (via cleaving the heterocycle break) flavonoids via the enzymes glucuronidase and sulphatase, producing metabolites that are primarily inert polar compounds that are rapidly excreted [164, 166–168]. Some flavonoids (e.g., apigenin, genistein, naringenin, and kaempferol) are more likely to undergo microflora degradation compared with others, resulting in lower bioavailability [169].…”