Table 1.
Interactions between dietary mediators, gut microbiota and CRC.
| Study (Reference) | Dietary Mediator | Type of Study | Species | Most Relevant Results |
|---|---|---|---|---|
| Dietary Fiber | ||||
| Lattimer et al. 2010 [93]) | Dietary Fiber (Arabinoxylan, Inulin, β-glucan, Pectin, Bran, Cellulose, Resistant Starch) | In vivo | Human | ↑ Excretion of bile acids, ↑ Production of fecal SCFAs ↑ Antioxidants ↓ Cancer prevalence |
| Zeng et al. 2014 [94] | Dietary Fiber | In vivo | Human | ↓ Fecal pH in the colon ↑ SCFA-producing gut bacteria ↑ Apoptosis of colon cancer cells ↓ Chronic inflammatory process and migration/ invasion of colon cancer cells |
| Deehan et al. 2020 [103] | Dietary Fiber | In vivo | Human | Modulation of the colon microbiota ↑ Saccharolytic fermentation ↑ Production of fecal SCFAs |
| Chen et al. 2013 [104] | Dietary Fiber | In vivo | Human | ↑ Production of SCFAs by healthy gut microbiota, ↓ Risk of advanced colorectal adenoma. |
| Burkitt et al. 1993 [108]; Bergman et al. 1990 [109]; Hamer et al. 2008 [110] |
Dietary Fiber | In vivo | Human/ Mouse |
↑ Production of fecal SCFAs (especially butyrate) ↓ Fecal pH in the colon, ↓ Pathogenic organism proliferation ↓ DNA damage induction ↑ Apoptosis of colon cancer cells ↓ Proliferation of colon cancer cells. |
| Fung et al. 2012 [111]; Neish et al. 2009 [112] |
Long-term dietary fiber intake | In vivo | Human | ↑ Abundance of Firmicutes abundance ↑ Immune modulatory and anti-inflammatory effects in the host |
| Bingham et al. 2003 [95] | Dietary Fiber | In vivo | Human | ↑ Total dietary fiber intake ↓ Risk of CRC |
| Schatzkin et al. 2007 [96] | Dietary Fiber (whole grains) | In vivo | Human | ↑ Whole grain food consumption ↓ Risk of CRC (modest) |
| Dahm et al. 2010 [97] | Dietary Fiber | In vivo | Human | ↑ Fiber intake ↓Risk of CRC |
| Hansen et al. 2012 [99] | Dietary Fiber (cereals) | In vivo | Human | ↑ Total dietary fiber ↓ Risk of CRC |
| Song M et al. 2018 [100] | Dietary Fiber (whole grains) | In vivo | Human | ↑ Survival rates of non-metastatic CRC |
| Moen et al. 2016 [101] | Dietary Fiber (inulin, cellulose, brewers spent grain) | In vivo | Mouse | Inulin intake change cecal microbiota ↓ Colonic tumorigenesis |
| Mehta et al. 2017 [102] | Dietary Fiber (whole grains) | In vivo | Human | ↓ Risk of developing Fusobacterium nucleatum-positive CRC |
| O’Keefe et al. 2015 [105] | Dietary fiber and fat | In vivo | Human | ↑ Saccharolytic fermentation ↑ Butyrogenesis ↓ Secondary bile acid synthesis ↓ Biomarkers of colon cancer risk |
| Donohoe et al. 2014 [106] | Dietary Fiber | In vivo | Mouse | ↑ Microbial fiber fermentation ↑ Butyrate production ↑ Protection against colorectal tumorigenesis. |
| Bishehsari et al. 2018 [107] | Dietary Fiber | In vivo | Mouse | ↑ SCFA-producing bacteria, ↓ Gut microbiota dysbiosis ↓ Polyposis incidence |
| Diets rich in polyunsaturated fatty acids | ||||
| Costantini et al. 2017 [114] | n-3 PUFAs | In vivo | Human/ Mouse |
↓ Relative abundance of Faecalibacterium ↑ Bacteroidetes and butyrate-producing bacteria (Lachnospiraceae family) |
| Cho et al. 2014 [116] | n-3 Fatty Acid Docosahexaenoic Acid and Butyrate | In vitro | Human | Epigenetic alterations (methylation of proapoptotic genes) ↑ Apoptosis of colon cancer cells |
| Chapkin et al. 2014 [117] | n-3 PUFAs | In vivo | Human/ Mouse |
Alterations in the plasma membrane of colon cancer cells Epigenetic alterations ↑ Risk of developing CRC. |
| Triff et al. 2015 [118] | n-3 PUFA & Fiber | In vivo | Human/ Mouse |
Regulation of nuclear receptor transcriptional activity ↓ Inflammatory cytokines ↑ Chemoprotection. |
| Hong et al. 2015 [119] | Fish oil & Butyrate | In vivo | Rat | ↑ Apoptosis of colon cancer cells ↓ Proliferation of colon cancer cells ↑ Protection against CRC |
| Lee et al. 2017 [121] | Fish oil & Butyrate | In vivo | Human | Modulation of CRC-related gene expression ↓ Inflammation ↑ Apoptosis of colon cancer cells |
| Chang et al. 1998 [125] | Fish oil & Fiber (pectin, cellulose) | In vivo | Rat | ↑ Apoptosis of colon cancer cells ↓ Proliferation of colon cancer cells ↓ Rate of CRC adenocarcinoma incidence |
| Cho et al. 2012 [127] | Fish oil & Pectin | In vivo | Rat | ↑ Apoptosis of colonocytes ↑ Chemoprotective capacity |
| Ng et al. 2005 [128] | Docosahexaenoic acid (DHA, 22:6 n-3) & butyrate | In vitro | Human | ↑ Mitochondrial lipid oxidation ↓ Mitochondrial membrane potential ↑ Apoptosis of colonocytes ↑ Chemoprotective effects |
| Sofi et al. 2019 [129] | Comparison of Meat-Based vs Pesco-Vegetarian Diets | In vivo | Human | Positive effect of pesco-vegetarian diet on gut microbiota ↓ Risk of CRC |
| Rani et al. 2017 [131]; Ran et al. 2014 [132]; Sebe et al. 2016 [133] |
n-3 PUFAs& 5-FU | In vivo | Mouse | ↓ Tumor burden and DNA damage ↓ Mucosal deterioration, ↑ Apoptosis ↓ 5-FU-related toxicity (intestinal mucositis) ↑ 5-FU anti-cancer activity |
| Ebadi et al. 2017 [134] | PUFAs & irinotecan | In vivo | Rat | Modulation of adipose tissue mitochondrial function ↓ 5-FU-associated side effects |
| Cai et al. 2014 [135] | n-3 PUFAs | In vitro | Human | ↑ Lipid peroxidation, Modulation of the inflammatory response ↑ Apoptosis ↓ Cytotoxicity by radiation therapy |
| Granci et al. 2013 [136] | Fish oil& & 5-FU, oxaliplatin and irinotecan | In vitro | Human | ↑ Apoptosis ↓ Cytotoxic effects of 5-FU, oxaliplatin and irinotecan. |
| Volpato et al. 2018 [113] | n-3 PUFAs | In vitro /In vivo |
Human/ Mouse |
↑ Butyrate-producing gut bacteria ↓ Inflammation; ↑ Apoptosis ↓ Proliferation of colon cancer cells |
| Watson et al. 2018 [115] | n-3 PUFAs | In vivo | Human | ↓ Gut microbiota dysbiosis ↓ Pathogenic gut bacteria ↑ SCFA-producing gut bacteria (Bifidobacterium, Roseburia and Lactobacillus). |
| Piazzi et al. 2014 [120] | Eicosapentaenoic Acid | In vivo | Mouse | ↑ Lactobacillus species in the gut microbiota ↓ Size of CRC tumors ↓ Proliferation colon cancer cells ↑ Apoptosis colon cancer cells |
| Song et al. 2015 [122] | n-3 PUFAs | In vivo | Human | ↓ Risk of microsatellite instability ↑ DNA repair systems mismatch pathways |
| Yang et al. 2015 [124] | n-3 PUFAs | In vivo | Human | Different PUFA composition between normal and cancerous tissues ↓ Inflammation in CRC tumorigenesis. |
| Song et al. 2017 [126] | Marine ω-3 PUFAs | In vivo | Human | ↑ Intake of marine ω-3 after CRC diagnosis ↓ Risk of CRC-specific mortality. |
| Aglago et al. 2020 [130] | n-3 PUFAs | In vivo | Human | Regular intake of fish at recommended levels ↓ Risk of CRC |
| Golkhalkhali et al. 2018 [137] | n-3 PUFAs & probiotic supplement | In vivo | Human | ↑ Tolerability of capecitabine/oxaliplatin chemotherapy ↑ Quality of life markers ↓ Chemotherapy-induced symptoms (diarrhea and fatigue) |
| Bioactive polyphenols | ||||
| Mileo et al. 2019 [139] | Polyphenols | In vivo/In vitro | Human/ Mouse |
↑ Gut microbiota balance ↓ Proliferation of colon cancer cells ↑ Apoptosis of colon cancer cells |
| Miene et al. 2009 [143] | Polyphenols (Apple) | In vitro | Human | Polyphenols are metabolized by colonic microbiota ↓ DNA damage induced by oxidative stress in colonic adenoma cells |
| Gibellini et al. 2011 [150] | Quercetin | In vivo | Human | ↓ Proliferation of colon cancer cells ↑ Apoptosis of colon cancer cells |
| Venancio et al. 2017 [151] | Polyphenols (Cocoplum) | In vitro | Human | Anti-inflammatory activity and pro-oxidant effects |
| Lee Y et al. 2014 [152] | Apigenin | In vitro | Human | ↓ Cell cycle progression ↓ Autophagy ↑ Apoptosis |
| Xavier et al. 2011 [160] | Polyphenols | In vitro | Human | ↑ Apoptosis (in combination with 5-FU) |
| Hakim et al. 2014 [161] | Gelam Honey and Ginger | In vitro | Human | ↑ Anticancer activity of 5-FU |
| Montrose et al. 2015 [162] | Black Raspberry (Anthocyanins, simple phenols, ellagic acid and quercetin) | In vivo | Mouse | ↓ Expression of proinflammatory cytokines (TNF-α and IL-1β) ↓ Plasma levels of COX-2 and prostaglandin E2 ↑ Chemopreventive effect |
| McFadden et al. 2015 [163] | Curcumin | In vivo | Mouse | ↑ Microbial diversity ↓ Colonic tumor burden ↑ Chemopreventive effect |
| Shakibaei et al. 2014 [164] | Curcumin | In vitro | Human | ↑ Chemosensitization to 5-FU treatment |
| Buhrmann et al. 215 [165] | Resveratrol | In vitro | Human | ↑ Chemosensitization to 5-FU treatment |
| Wang et al. 2015 [166] | Resveratrol | In vitro | Human | ↓ Drug resistance (down-regulation of multi-drug resistant protein 1), ↓ Activation of NF-κB signaling ↓ Transcriptional activity of the cAMP-sensitive element |
| Paul et al. 2010 [153] | Pterostilbene (Blueberries) | In vivo | Rat | ↓ Colon tumorigenesis by regulating the Wnt/b-catenin-signaling pathway ↓ Inflammatory responses. |
| Cui et al. 2010 [154] | Resveratrol | In vivo | Mouse | ↓ Colitis-driven colon cancer incidence |
| Rodríguez-Ramiro et al. 2013 [155] | Polyphenols (Cocoa) | In vivo | Rat | Anti-inflammatory effect on the colonic tissue Chemoprevention in the early stages |
| Simons et al. 2009 [157] |
Flavonol, Flavone and Catechin | In vivo | Human | ↓ Risk of CRC |
| Zamora-Ros et al. 2017 [158] | Flavonoid | In vivo | Human | No association between regular dietary intake of flavonoids and CRC risk |
| Sánchez et al. 2019 [148]; Cueva et al. 2020 [149] | Red wine Polyphenols | In vivo | Human | Modulation of the gut microbiota composition ↓ Growth of pathogenic bacterial species (F. nucleatum and P. Gingivalis) ↓ Adhesion to oral cells ↓ Risk of CRC |
| Probiotics | ||||
| Hatakka et al. 2008 [169] | Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii ssp. | In vivo | Human | Fecal counts of Lactobacilli and Propionibacteria ↓ β-glucosidase activity ↑ CRC prevention |
| Vinderola et al. 2006 [171] | Lactobacillus kefiranofaciens | In vivo | Human | Regulation of the immune system, ↑ Phagocytosis of tumor cells in early stages. |
| Galdeano et al. 2007 [172] |
Lactobacillus casei | In vivo | Mouse | Induction of innate immunity influencing the clonal expansion of IgA B-cell population, ↓ Risk of CRC. |
| Bozkurt et al. 2019 [173] | Bifidobacterium animalis subsp. lactis | In vivo | Human/ Mouse |
↑ Production mycosporin-like amino acids Modulation of the immune system to regulate the proliferation and differentiation of intestinal epithelial cells, macrophages, lymphocytes and cytokine production |
| Liu et al. 2011 [174] | Lactobacillus plantarum, Lactobacillus acidophilus & Bifidobacterium Longum | In vivo | Human | ↑ Integrity of the intestinal barrier, ↑ Gut microbiota balance ↓ Post-operative infection rate |
| Rafter et al. 2007 [175] | Lactobacillus rhamnosus & Bifidobacterium lactis | In vivo | Human | Modulation of the gut microbiota composition ↓ Intestinal permeability, ↓ Cancer biomarkers (cell proliferation). |
| Hibberd et al. 2017 [176] | Bifidobacterium animalis subsp. lactis Bl-04 & Lactobacillus acidophilus NCFM | In vivo | Human | ↑ Abundance of butyrate-producing bacteria in tumor, mucosa and fecal samples |
| Liang et al. 2016 [177] | Bifidobacterium | In vivo | Human | ↓ Gut microbiota dysbiosis in CRC patients |
| Wan et al. 2014 [178] | Lactobacillus delbrueckii | In vitro | Cell line SW620 | ↓ Proliferation of colon cancer cells ↑ Apoptosis of colon cancer cells (via caspase 3 pathway) |
| Konishi et al. 2016 [179] | Lactobacillus casei strain ATCC 334 | In vivo | Human | ↑ Production of ferrichrome ↑ Apoptosis of colon cancer cells (via JNK pathway) ↓ Progression of CRC |
| Chang et al. 2018 [182] |
Lactobacillus casei Variety rhamnosus & 5-FU/oxaliplatin | In vivo | Mouse | ↓ Intestinal mucositis derived from anticancer treatment. |
| Ding et al. 2018 [183]; Lee et al. 2016 [184]; Routy et al. 2018 [185] |
Bifidobacterium & PD-1-based immunotherapy |
In vivo | Human/ Mouse |
↓ Tumor growth ↓ Side effects induced by PD-1-based immunotherapy |
| Osterlund et al. 2007 [186] | Lactobacillus rhamnosus | In vivo | Human | ↓ Side effects (severe diarrhea, abdominal distress) induced by chemotherapy. |