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

doi:10.1016/j.redox.2021.101862

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

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

75 Downloads (Pure)

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 language	English
Article number	101862
Pages (from-to)	1-11
Number of pages	11
Journal	Redox Biology
Volume	40
Early online date	12 Jan 2021
DOIs	https://doi.org/10.1016/j.redox.2021.101862
Publication status	Published (in print/issue) - 30 Apr 2021

Bibliographical note

Funding 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.

Publisher Copyright:
© 2021 The Authors

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

Funding 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. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.redox.2021.101862

1-s2.0-S2213231721000100-mainFinal published version, 3.36 MBLicence: CC BY

Cite this

Dobani, S., Latimer, C., McDougall, G., Allwood, J. W., Pereira-Caro, G., Moreno-Rojas, J. M., Ternan, N. G., Pourshahidi, L. K., Lawther, R., Tuohy, K., Del Rio, D., O'Connor, G., Rowland, I., Mazyad Almutairi, T., Crozier, A., & Gill, C. IR. (2021). Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cells. Redox Biology, 40, 1-11. Article 101862. https://doi.org/10.1016/j.redox.2021.101862

@article{a3fdd322c599459f846a97839ddb2062,

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

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 (\textasciitilde{}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.",

keywords = "Colon cancer, DNA damage, Fecal fermentation, Gastrointestinal microbiota, Ileostomy, Phenolic catabolites, Raspberry (poly)phenols",

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

note = "Funding 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. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

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doi = "10.1016/j.redox.2021.101862",

language = "English",

volume = "40",

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Dobani, S, Latimer, C, McDougall, G, Allwood, JW, Pereira-Caro, G, Moreno-Rojas, JM, Ternan, NG , Pourshahidi, LK, Lawther, R, Tuohy, K, Del Rio, D, O'Connor, G, Rowland, I, Mazyad Almutairi, T, Crozier, A & Gill, CIR 2021, 'Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cells', Redox Biology, vol. 40, 101862, pp. 1-11. https://doi.org/10.1016/j.redox.2021.101862

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T1 - Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cells

AU - Dobani, Sara

AU - Latimer, Cheryl

AU - McDougall, Gordon

AU - Allwood, James William

AU - Pereira-Caro, Gema

AU - Moreno-Rojas, Jose manuel

AU - Ternan, Nigel G

AU - Pourshahidi, L. Kirsty

AU - Lawther, Roger

AU - Tuohy, Kieran

AU - Del Rio, Daniele

AU - O'Connor, Gloria

AU - Rowland, Ian

AU - Mazyad Almutairi, Tahani

AU - Crozier, Alan

AU - Gill, Chris IR

N1 - Funding 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. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/30

Y1 - 2021/4/30

N2 - 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.

AB - 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.

KW - Colon cancer

KW - DNA damage

KW - Fecal fermentation

KW - Gastrointestinal microbiota

KW - Ileostomy

KW - Phenolic catabolites

KW - Raspberry (poly)phenols

UR - https://pubmed.ncbi.nlm.nih.gov/33486151/

UR - https://www.scopus.com/pages/publications/85099987404

U2 - 10.1016/j.redox.2021.101862

DO - 10.1016/j.redox.2021.101862

M3 - Article

C2 - 33486151

SN - 2213-2317

VL - 40

SP - 1

EP - 11

JO - Redox Biology

JF - Redox Biology

M1 - 101862

ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

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VALGUT: phenyl-ϒ-valerolactones are microbiota-derived compounds that can impact gut health

Cite this

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Student theses

VALGUT: phenyl-ϒ-valerolactones are microbiota-derived compounds that can impact gut health

Cite this