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The bioavailability of apigenin-7-glucoside is influenced by human intestinal microbiota in rats
Laura Hanske1, Gunnar Loh, Silke Sczesny
1German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Gastrointestinal Microbiology, 14558 Nuthetal, Germany.
Abstract:
We investigated the impact of human intestinal microbiota on bioavailability of the flavone apigenin-7-glucoside (A7G) by comparing germ-free and human microbiota-associated (HMA) rats. First, the ability of the human intestinal microbiota to convert A7G was proven in vitro by incubating A7G with fecal suspensions. Apigenin, naringenin, and 3-(4-hydroxyphenyl)propionic acid were formed as main metabolites. After application of A7G to germ-free rats, apigenin, luteolin, and their conjugates were detected in urine and feces. In HMA rats, naringenin, eriodictyol, phloretin, 3-(3,4-dihydroxyphenyl)propionic acid, 3-(4-hydroxyphenyl)propionic acid, 3-(3-hydroxyphenyl)propionic acid, and 4-hydroxycinnamic acid in their free and conjugated forms were additionally formed. In whole-blood samples from germ-free and HMA rats, only apigenin conjugates and phloretin, respectively, were detected. The total excretion of A7G and its metabolites within 48 h was similarly low in both germ-free and HMA rats, with 11 and 13% of the A7G dose, respectively. In germ-free rats, A7G metabolites dominated by apigenin and its conjugates were mainly excreted with feces. In contrast, the compounds in HMA rats were predominantly recovered from urine, 3-(4-hydroxyphenyl)propionic acid being the main metabolite. The ability of selected gut bacteria and the host intestinal mucosa to deglycosylate A7G was tested using cell extracts. Apigenin was formed by cytosolic extracts of Eubacterium ramulus and Bacteroides distasonis and by the microsomal fraction of the small intestinal mucosa of rats. Overall, human intestinal microbiota largely contributed to A7G metabolism, indicating its influence on the bioactivity of flavones.
Insights
Human gut microbiota significantly alters flavone metabolism, producing diverse metabolites in associated rats compared to germ-free models. This impacts flavone bioavailability and bioactivity.
Area of Science:
- Pharmacology
- Microbiology
- Nutritional Science
Background:
- Flavones, like apigenin-7-glucoside (A7G), are plant compounds with potential health benefits.
- Their bioavailability and efficacy are influenced by host-microbiota interactions.
- Understanding A7G metabolism is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the impact of human intestinal microbiota on the bioavailability and metabolism of apigenin-7-glucoside (A7G).
- To compare A7G metabolism in germ-free rats versus human microbiota-associated (HMA) rats.
Main Methods:
- In vitro incubation of A7G with fecal suspensions to identify metabolites.
- Administration of A7G to germ-free and HMA rats, followed by analysis of urine, feces, and blood.
- Enzymatic assays using gut bacteria and rat intestinal mucosa extracts to assess deglycosylation.
Main Results:
- Human intestinal microbiota converted A7G into apigenin, naringenin, and 3-(4-hydroxyphenyl)propionic acid in vitro.
- HMA rats exhibited a broader range of A7G metabolites, including naringenin, eriodictyol, and phloretin, compared to germ-free rats.
- While total A7G excretion was low in both groups, metabolite profiles differed significantly, with HMA rats primarily excreting metabolites in urine.
Conclusions:
- Human intestinal microbiota profoundly influences A7G metabolism, leading to diverse metabolite profiles.
- Microbiota-driven metabolism significantly impacts the bioavailability and potential bioactivity of flavones.
- Targeting gut microbiota could be a strategy to modulate flavone efficacy.
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