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.
|Number of pages||11|
|Early online date||12 Jan 2021|
|Publication status||Published (in print/issue) - 30 Apr 2021|
Bibliographical noteFunding Information:
We would like to thank the volunteers for participating in the study. C.I.R.G. R.L. and A.C. acknowledge funding from the National Processed Raspberry Council who had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. G.McD. and J.W.A. acknowledge funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) Division. G.McD. acknowledge funding from BachBerry (Project No. FP7-613793). G.P.-C. was supported by a postdoctoral research contract ?Juan de la Cierva-Incorporaci?n? funded by the Spanish Ministry of Economy and Competitiveness (FJCI-2015-26433). T.M.A. and A.C. were supported by the Researchers Supporting Project (RSP-2020/273) of King Saud University, Riyadh, Saudi Arabia.
© 2021 The Authors
Copyright 2021 Elsevier B.V., All rights reserved.
- Colon cancer
- DNA damage
- Fecal fermentation
- Gastrointestinal microbiota
- Phenolic catabolites
- Raspberry (poly)phenols