Abstract
Diets rich in fruit and vegetables are associated with a decreased incidence of colorectal cancer (CRC) due, in part, to the bioactive (poly)phenolic components and their microbiota-mediated metabolites. This study investigated how such compounds, derived from ingested raspberries in the gastrointestinal tract, may exert protective effects by reducing DNA damage. Ileal fluids collected pre- and post-consumption of 300 g of raspberries by ileostomists (n = 11) were subjected to 24 h ex vivo fermentation with fecal inoculum to simulate interaction with colonic microbiota. The impact of fermentation on (poly)phenolics in ileal fluid was determined and the bioactivity of ileal fluids pre- and post fermentation investigated. (Poly)phenolic compounds including sanguiin H-6, sanguiin H-10 and cyanidin-3-O-sophoroside decreased significantly during fermentation while, in contrast, microbial catabolites, including 3-(3′-hydroxyphenyl)propanoic acid, 3-hydroxybenzoic acid and benzoic acid increased significantly. The post-raspberry ileal fermentate from 9 of the 11 ileostomates significantly decreased DNA damage (~30%) in the CCD 841 CoN normal cell line using an oxidative challenge COMET assay. The raspberry ileal fermentates also modulated gene expression of the nuclear factor 2–antioxidant responsive element (Nrf2-ARE) pathway involved in oxidative stress cytoprotection, namely Nrf2, NAD(P)H dehydrogenase, quinone-1 and heme oxygenase-1. Four of the phenolic catabolites were assessed individually, each significantly reducing DNA damage from an oxidative challenge over a physiologically relevant 10–100 μM range. They also induced a differential pattern of expression of key genes in the Nrf2-ARE pathway in CCD 841 CoN cells. The study indicates that the colon-available raspberry (poly)phenols and their microbial-derived catabolites may play a role in protection against CRC in vivo.
Highlights
IntroductionNumerous studies have emulated effects on the GI tract using a variety of in vitro models [16] including INFOGEST which advocates a stand ardised model including buccal simulation [17]
In the current study use was made of ileal fluid, which provides a source of dietary compounds not absorbed by the small intestine that would become available for interaction with the gut microbiota and the colonic epithelium
The ileal fluid samples were subjected to ex-vivo fecal fermentation and analysed for changes in phytochemical compo sition, activity in protection against DNA damage and activation of the Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway
Summary
Numerous studies have emulated effects on the GI tract using a variety of in vitro models [16] including INFOGEST which advocates a stand ardised model including buccal simulation [17]. These models demon strate that (poly)phenols have different stabilities and are likely available in amounts that could modulate physiological processes. They compare potential in-gut availability but cannot comprehensively mimic the dynamic and active processes associated with the digestion of food when consumed by humans [18]. Ileostomy-based bioavail ability studies provide a unique insight into events taking place in the GI tract, facilitating identification of compounds which, in individuals with an intact colon, would pass from the small to the large intestine and exert their effects [19,20,21,22,23,24,25]
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