A mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota

Giulia Piazzi, Anna Prossomariti, Maurizio Baldassarre, Claudio Montagna, Paola Vitaglione, Vincenzo Fogliano, Elena Biagi, Marco Candela, Patrizia Brigidi, Tiziana Balbi, Alessandra Munarini, Andrea Belluzzi, Milena Pariali, Franco Bazzoli, Luigi Ricciardiello

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.

LanguageEnglish
Article number140
JournalFrontiers in Oncology
Volume9
Issue numberMAR
DOIs
Publication statusPublished - 12 Mar 2019

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Mediterranean Diet
Colorectal Neoplasms
High Fat Diet
Azoxymethane
Apoptosis
Dysbiosis
RNA Sequence Analysis
Neoplasms
Gastrointestinal Microbiome
Microbiota
Incidence
In Situ Nick-End Labeling
Western Diet
Mass Spectrometry
Fatty Acids
Immunohistochemistry
Fats
Cell Proliferation
Gene Expression

Keywords

  • Chemoprevention
  • Colorectal cancer
  • Mediterranean diet
  • Microbiota
  • Omega-3

Cite this

Piazzi, Giulia ; Prossomariti, Anna ; Baldassarre, Maurizio ; Montagna, Claudio ; Vitaglione, Paola ; Fogliano, Vincenzo ; Biagi, Elena ; Candela, Marco ; Brigidi, Patrizia ; Balbi, Tiziana ; Munarini, Alessandra ; Belluzzi, Andrea ; Pariali, Milena ; Bazzoli, Franco ; Ricciardiello, Luigi. / A mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota. In: Frontiers in Oncology. 2019 ; Vol. 9, No. MAR.
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title = "A mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota",
abstract = "Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100{\%} was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.",
keywords = "Chemoprevention, Colorectal cancer, Mediterranean diet, Microbiota, Omega-3",
author = "Giulia Piazzi and Anna Prossomariti and Maurizio Baldassarre and Claudio Montagna and Paola Vitaglione and Vincenzo Fogliano and Elena Biagi and Marco Candela and Patrizia Brigidi and Tiziana Balbi and Alessandra Munarini and Andrea Belluzzi and Milena Pariali and Franco Bazzoli and Luigi Ricciardiello",
year = "2019",
month = "3",
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journal = "Frontiers in Oncology",
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Piazzi, G, Prossomariti, A, Baldassarre, M, Montagna, C, Vitaglione, P, Fogliano, V, Biagi, E, Candela, M, Brigidi, P, Balbi, T, Munarini, A, Belluzzi, A, Pariali, M, Bazzoli, F & Ricciardiello, L 2019, 'A mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota', Frontiers in Oncology, vol. 9, no. MAR, 140. https://doi.org/10.3389/fonc.2019.00140

A mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota. / Piazzi, Giulia; Prossomariti, Anna; Baldassarre, Maurizio; Montagna, Claudio; Vitaglione, Paola; Fogliano, Vincenzo; Biagi, Elena; Candela, Marco; Brigidi, Patrizia; Balbi, Tiziana; Munarini, Alessandra; Belluzzi, Andrea; Pariali, Milena; Bazzoli, Franco; Ricciardiello, Luigi.

In: Frontiers in Oncology, Vol. 9, No. MAR, 140, 12.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota

AU - Piazzi, Giulia

AU - Prossomariti, Anna

AU - Baldassarre, Maurizio

AU - Montagna, Claudio

AU - Vitaglione, Paola

AU - Fogliano, Vincenzo

AU - Biagi, Elena

AU - Candela, Marco

AU - Brigidi, Patrizia

AU - Balbi, Tiziana

AU - Munarini, Alessandra

AU - Belluzzi, Andrea

AU - Pariali, Milena

AU - Bazzoli, Franco

AU - Ricciardiello, Luigi

PY - 2019/3/12

Y1 - 2019/3/12

N2 - Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.

AB - Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.

KW - Chemoprevention

KW - Colorectal cancer

KW - Mediterranean diet

KW - Microbiota

KW - Omega-3

U2 - 10.3389/fonc.2019.00140

DO - 10.3389/fonc.2019.00140

M3 - Article

VL - 9

JO - Frontiers in Oncology

T2 - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

IS - MAR

M1 - 140

ER -