Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cells

Sara Dobani, Cheryl Latimer, Gordon McDougall, James William Allwood, Gema Pereira-Caro, Jose manuel Moreno-Rojas, Nigel G Ternan, L. Kirsty Pourshahidi, Roger Lawther, Kieran Tuohy, Daniele Del Rio, Gloria O'Connor, Ian Rowland, Tahani Mazyad Almutairi, Alan Crozier, Chris IR Gill

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1 Citation (Scopus)
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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.
Original languageEnglish
Article number101862
Pages (from-to)1-11
Number of pages11
JournalRedox Biology
Volume40
Early online date12 Jan 2021
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Colon cancer
  • DNA damage
  • Fecal fermentation
  • Gastrointestinal microbiota
  • Ileostomy
  • Phenolic catabolites
  • Raspberry (poly)phenols

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