Journal
REDOX BIOLOGY
Volume 40, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2021.101862
Keywords
Ileostomy; Gastrointestinal microbiota; Raspberry (poly)phenols; Phenolic catabolites; Fecal fermentation; DNA damage; Colon cancer
Categories
Funding
- National Processed Raspberry Council
- Scottish Government's Rural and Environment Science and Analytical Services (RESAS) Division
- BachBerry [FP7-613793]
- Juan de la Cierva-Incorporacion - Spanish Ministry of Economy and Competitiveness [FJCI-2015-26433]
- Researchers Supporting Project of King Saud University, Riyadh, Saudi Arabia [RSP-2020/273]
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Research suggests that the bioactive (poly)phenolic compounds from ingested raspberries, along with their microbial-derived catabolites, may play a role in protecting against colorectal cancer by reducing DNA damage.
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-sophomside 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 (similar to 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 mu M 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.
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