Abstract
The bioactivity of dietary polyphenols depends upon gastrointestinal and hepatic metabolism of secondary microbial phenolic metabolites generated via colonic microbiota-mediated biotransformation. A polyphenol-rich potato extract (PRPE) containing chlorogenic, caffeic, and ferulic acids and rutin was digested in a dynamic multi-reactor gastrointestinal simulator of the human intestinal microbial ecosystem (GI model). Simulated digestion showed extensive degradation of the parent compounds and the generation of microbial phenolic metabolites. To characterize the transport and metabolism of microbial phenolic metabolites following digestion, a co-culture of intestinal Caco-2 and hepatic HepG2 cells was exposed to the PRPE-derived digests obtained from the colonic vessels. Following a 2 h incubation of the digesta with the Caco-2/HepG2 co-cultures, approximately 10–15% of ferulic, dihydrocaffeic, and dihydroferulic acids and 3–5% of 3-hydroxybenzoic, 3-hydroxyphenylpropionic, and coumaric acids were observed in the basolateral side, whereas 3-hydroxyphenylacetic acid, phenylpropanoic acid, and cinnamic acid were not detected. Subsequent HepG2 cellular metabolism led to major increases in ferulic, dihydrocaffeic, 3-hydroxyphenylpropionic, and coumaric acids ranging from 160–370%. These findings highlight the importance of hepatic metabolism towards the generation of secondary metabolites of polyphenols despite low selective Caco-2 cellular uptake of microbial phenolic metabolites.
Highlights
There is increasing evidence from epidemiological studies and randomized clinical trials showing a strong association between consumption of polyphenols and reduced risk of several chronic diseases such as type 2 diabetes, cardiovascular disease, and some types of cancer [1]
To examine the production of colonic microbial metabolites of polyphenols, we utilized a dynamic multi-reactor gastrointestinal simulator of the human intestinal microbial ecosystem (GI) digestion model, which consists of five interconnected vessels representing the stomach and small intestine, as well as reactors pertaining to the ascending, transverse, and descending colon inoculated with human fecal matter [12,13,14]
The present results indicate that 3-hydroxybenzoic acid, one of the major products of gut microbiota metabolism, can be present following post-intestinal and hepatic metabolism
Summary
There is increasing evidence from epidemiological studies and randomized clinical trials showing a strong association between consumption of polyphenols and reduced risk of several chronic diseases such as type 2 diabetes, cardiovascular disease, and some types of cancer [1]. The predominant dietary sources of polyphenols are primarily plant foods that are consumed regularly in large amounts, such as potatoes that are an important food staple in many populations [2]. Potatoes are a good source of common dietary polyphenols—including chlorogenic acid (CGA), caffeic acid (CA), ferulic acid (FA), and rutin (RU)—which are linked with health-promoting properties [3,4]. Due to their glycosidic linkages, polyphenols are generally poorly absorbed in the small intestine and so the majority of these compounds reach the colon where glycosides are cleaved by microbiota to generate the aglycon [6]. To examine the production of colonic microbial metabolites of polyphenols, we utilized a dynamic multi-reactor gastrointestinal simulator of the human intestinal microbial ecosystem (GI) digestion model, which consists of five interconnected vessels representing the stomach and small intestine, as well as reactors pertaining to the ascending, transverse, and descending colon inoculated with human fecal matter [12,13,14]
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