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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.

SUBMITTER: Piazzi G

PROVIDER: S-EPMC6423077 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota.

Piazzi Giulia G Prossomariti Anna A Baldassarre Maurizio M Montagna Claudio C Vitaglione Paola P Fogliano Vincenzo V Biagi Elena E Candela Marco M Brigidi Patrizia P Balbi Tiziana T Munarini Alessandra A Belluzzi Andrea A Pariali Milena M Bazzoli Franco F Ricciardiello Luigi L

Frontiers in oncology 20190312

<b>Objectives:</b> 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). <b>Materials and Methods:</b> Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm ...[more]

PMID: 30915275

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Project description:There is increasing evidence for the interaction between gut microbiome, diet, and health. It is known that dysbiosis is related to disease and that most of the times this imbalances in gut microbial populations can be promoted through diet. Western dietary habits, which are characterized by high intakes of calories, animal proteins, saturated fats, and simple sugars have been linked with higher risk of obesity, diabetes, cancer, and cardiovascular disease. However, little is known about the impact of dietary patterns, dietary components, and nutrients on gut microbiota in healthy people. The aim of our study is to determine the effect of nutrient compounds as well as adherence to a dietary pattern, as the Mediterranean diet (MD) on the gut microbiome of healthy adults. Consequently, gut microbiota composition in healthy individuals, may be used as a potential biomarker to identify nutritional habits as well as risk of disease related to these habits. Dietary information from healthy volunteers (n = 27) was recorded using the Food Frequency Questionnaire. Adherence to the MD was measured using the PREDIMED test. Microbiota composition and diversity were obtained by 16S rRNA gene sequencing and specific quantitative polymerase chain reaction. Microbial metabolic activity was determined by quantification of short chain fatty acids (SCFA) on high performance liquid chromatography (HPLC). The results indicated that a higher ratio of Firmicutes-Bacteroidetes was related to lower adherence to the MD, and greater presence of Bacteroidetes was associated with lower animal protein intake. High consumption of animal protein, saturated fats, and sugars affected gut microbiota diversity. A significant higher presence of Christensenellaceae was found in normal-weight individuals compared to those who were overweight. This was also the case in volunteers with greater adherence to the MD compared to those with lower adherence. Butyricimonas, Desulfovibrio, and Oscillospira genera were associated with a BMI <25 and the genus Catenibacterium with a higher PREDIMED score. Higher bifidobacterial counts, and higher total SCFA were related to greater consumption of plant-based nutrients, such as vegetable proteins and polysaccharides. Better adherence to the MD was associated with significantly higher levels of total SCFA. Consequently, diet and specific dietary components could affect microbiota composition, diversity, and activity, which may have an effect on host metabolism by increasing the risk of Western diseases.

Project description:Abstract Objectives While it is known that specific components of diet namely fiber, fatty acids, or polyphenols can modulate the gut microbiota, literature describing the influence of a specific dietary pattern such as the Mediterranean Diet (MD) on enteric microbiota especially in relation to health are scarce. The aim of this study was to evaluate whether a MD intervention and the adherence to MD influences the gut fecal microbial composition in firefighters participating in Feeding America's Bravest, a randomized control trial. Methods Participants were firefighters who received a MD Nutritional Intervention (n = 22) or standard dietary advice (n = 24) as part of a cluster-randomized, controlled trial for 12 months. A lifestyle and food frequency questionnaire was administered and adherence scores to the MD were calculated (PREDIMED and Modified MD Score). Bacterial 16S rRNA sequencing was performed from fecal samples, and the microbial composition was analyzed with a bioinformatics pipeline implemented using QIIME 2. R software was used for linear modeling. Results The predominant bacteria phyla in both groups were Firmicutes (52.9%), Bacteroidetes (39.8%), Proteobacteria (3.5%), and Actinobacteria (2.0%). A significant increase in the genus Prevotella was found in those in the intervention group (1.45 log-fold, P = 0.018) compared to controls. Furthermore, linear modeling revealed that higher adherence to MD was associated with lower abundance of Lachnospiriceae UCG-010 (R2 = 0.205, P < 0.001) and Eubacterium ventriosum group (R2 = 0.101, P = 0.016). There were no significant differences in alpha or beta diversity between the control and intervention group. Conclusions A MD intervention as well as higher adherence influence gut microbiota composition; specifically, Prevotella, a genus previously associated with plant-rich diets, was significantly higher in the intervention group. Additionally, higher adherence to MD was associated with multiple genera of bacteria previously involved in SCFA production, which may help elucidate the beneficial effects of the Mediterranean Diet. Funding Sources Grant support: EMW-2014-FP-00612, US Department of Homeland Security and Ohio University Startup funds. Trial Registration Number: NCT02941757

Dataset Information

A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota.

Publications

A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota.

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