Fecal microbiome as determinant of the effect of diet on colorectal cancer risk: comparison of meat-based versus pesco-vegetarian diets (the MeaTIc study)

Francesco Sofi, Monica Dinu, Giuditta Pagliai, Fabrice Pierre, Francoise Gueraud, Jildau Bowman, Philippe Gerard, Vincenzo Longo, Lisa Giovannelli, Giovanna Caderni, Carlotta de Filippo, Francesco Sofi, Monica Dinu, Giuditta Pagliai, Fabrice Pierre, Francoise Gueraud, Jildau Bowman, Philippe Gerard, Vincenzo Longo, Lisa Giovannelli, Giovanna Caderni, Carlotta de Filippo

Abstract

Background: Convincing evidence suggests that the risk of colorectal cancer (CRC) is increased by the typical Western diet characterized by high consumption of red and processed meat. In addition, some epidemiological studies suggest a reduction in the risk of CRC associated with fish consumption. The role of the gut microbiome in this diet-associated risk is not well understood.

Methods/design: This is a randomized parallel open clinical trial comprising a total of 150 clinically healthy subjects randomly assigned to three groups: a meat-based diet of which 4 portions per week are red meat (1 portion = 150 g), 3 portions per week are processed meat (1 portion = 50 g), and 1 portion per week is poultry (1 portion = 150 g), for a total amount of 900 g per week of meat and derivatives; a meat-based diet supplemented with alpha-tocopherol; and a pesco-vegetarian diet excluding fresh and processed meat and poultry, but which includes 3 portions per week of fish for a total amount of 450 g per week. Each intervention will last 3 months. The three diets will be isocaloric and of three different sizes according to specific energy requirements. Anthropometric measurements, body composition, and blood and fecal samples will be obtained from each participant at the beginning and end of each intervention phase. The measure of the primary outcome will be the change from baseline in DNA damage induced by fecal water using the comet assay in a cellular model. Secondary outcome measures will be changes in the profile of fecal microbiomes, global fecal and urinary peroxidation markers, and neoplastic biomarkers.

Discussion: Although epidemiological data support the promoting role of meat and the possible protective role of fish in colon carcinogenesis, no study has directly compared dietary profiles characterized by the presence of these two food groups and the role of the gut microbiome in these diet-associated CRC risks. This study will test the effect of these dietary profiles on validated CRC risk biomarkers.

Trial registration: ClinicalTrials.gov, NCT03416777. Registered on 3 May 2018.

Keywords: Colorectal cancer; Diet; Intestinal microbiome; Meat; Neoplastic disease; Prevention; Vegetarian.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Time schedule of enrollment, interventions, and assessments for participants
Fig. 2
Fig. 2
Organization of the intervention study

References

    1. Perdue DG, Haverkamp D, Perkins C, Daley CM, Provost E. Geographic variation in colorectal cancer incidence and mortality, age of onset, and stage at diagnosis among American Indian and Alaska Native people, 1990-2009. Am J Public Health. 2014;104:S404–S414. doi: 10.2105/AJPH.2013.301654.
    1. World Cancer Research Fund (WCRF)/American Institute for Cancer Research. Diet, nutrition, physical activity and cancer: a global perspective. Continuous Update Project Expert Report. London: WCRF; 2018. http://.
    1. Vieira AR, Abar L, Chan DSM, Vingeliene S, Polemiti E, Stevens C, Greenwood D, Norat T. Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Ann Oncol. 2017;28:1788–1802. doi: 10.1093/annonc/mdx171.
    1. Bastide NM, Chenni F, Audebert M, Santarelli RL, Taché S, Naud N, Baradat M, Jouanin I, Surya R, Hobbs DA, Kuhnle GG, Raymond-Letron I, Gueraud F, Corpet DE, Pierre FH. A central role for heme iron in colon carcinogenesis associated with red meat intake. Cancer Res. 2015;75:870–879. doi: 10.1158/0008-5472.CAN-14-2554.
    1. Santarelli RL, Vendeuvre JL, Naud N, Taché S, Guéraud F, Viau M, Genot C, Corpet DE, Pierre FH. Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats. Cancer Prev Res (Phila) 2010;3:852–864. doi: 10.1158/1940-6207.CAPR-09-0160.
    1. Bastide N, Morois S, Cadeau C, Kangas S, Serafini M, Gusto G, Dossus L, Pierre FH, Clavel-Chapelon F, Boutron-Ruault MC. Heme iron intake, dietary antioxidant capacity, and risk of colorectal adenomas in a large cohort study of French women. Cancer Epidemiol Biomark Prev. 2016;25:640–647. doi: 10.1158/1055-9965.EPI-15-0724.
    1. Diallo A, Deschasaux M, Partula V, Latino-Martel P, Srour B, Hercberg S, Galan P, Fassier P, Guéraud F, Pierre FH, Touvier M. Dietary iron intake and breast cancer risk: modulation by an antioxidant supplementation. Oncotarget. 2016;7:79008–79016. doi: 10.18632/oncotarget.12592.
    1. Martin OC, Lin C, Naud N, Tache S, Raymond-Letron I, Corpet DE, Pierre FH. Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats. Nutr Cancer. 2015;67:119–125. doi: 10.1080/01635581.2015.976317.
    1. Martin OCB, Olier M, Ellero-Simatos S, Naud N, Dupuy J, Huc L, Taché S, Graillot V, Levêque M, Bézirard V, Héliès-Toussaint C, Estrada FBY, Tondereau V, Lippi Y, Naylies C, Peyriga L, Canlet C, Davila AM, Blachier F, Ferrier L, Boutet-Robinet E, Guéraud F, Théodorou V, Pierre FHF. Haeme iron reshapes colonic luminal environment: impact on mucosal homeostasis and microbiome through aldehyde formation. Microbiome. 2019;7:72. doi: 10.1186/s40168-019-0685-7.
    1. Bultman SJ. Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention. Clin Cancer Res. 2014;20:799–803. doi: 10.1158/1078-0432.CCR-13-2483.
    1. O'Keefe SJ. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13:691–706. doi: 10.1038/nrgastro.2016.165.
    1. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107:14691–14696. doi: 10.1073/pnas.1005963107.
    1. Federici E, Prete R, Lazzi C, Pellegrini N, Moretti M, Corsetti A, Cenci G. Bacterial composition, genotoxicity, and cytotoxicity of fecal samples from individuals consuming omnivorous or vegetarian diets. Front Microbiol. 2017;8:300. doi: 10.3389/fmicb.2017.00300.
    1. Rafter J, Bennett M, Caderni G, Clune Y, Hughes R, Karlsson PC, Klinder A, O'Riordan M, O'Sullivan GC, Pool-Zobel B, Rechkemmer G, Roller M, Rowland I, Salvadori M, Thijs H, Van Loo J, Watzl B, Collins JK. Dietary symbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr. 2007;85:488–496. doi: 10.1093/ajcn/85.2.488.
    1. Albanese D, De Filippo C, Cavalieri D, Donati C. Explaining diversity in metagenomic datasets by phylogenetic-based feature weighting. PLOS Comput Biol. 2015;11:e1004186. doi: 10.1371/journal.pcbi.1004186.
    1. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60. doi: 10.1186/gb-2011-12-6-r60.
    1. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563. doi: 10.1038/nature12820.
    1. Pierre FH, Martin OC, Santarelli RL, Taché S, Naud N, Guéraud F, Audebert M, Dupuy J, Meunier N, Attaix D, Vendeuvre JL, Mirvish SS, Kuhnle GC, Cano N, Corpet DE. Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers. Am J Clin Nutr. 2013;98:1255–1262. doi: 10.3945/ajcn.113.061069.
    1. Guéraud F, Taché S, Steghens JP, Milkovic L, Borovic-Sunjic S, Zarkovic N, Gaultier E, Naud N, Héliès-Toussaint C, Pierre F, Priymenko N. Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats. Free Radic Biol Med. 2015;83(1):92–200.
    1. Rhodes JM, Campbell BJ. Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared. Trends Mol Med. 2002;8:10–16. doi: 10.1016/S1471-4914(01)02194-3.
    1. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J. 1998;12:1063–1073. doi: 10.1096/fasebj.12.12.1063.
    1. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans . Red meat and processed meat. Lyon: International Agency for Research on Cancer; 2018.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit