Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer
Abstract
1. Introduction
1.1. Impact of Diet on Colorectal Cancer
1.2. Intestinal Microbiota and Human Health
2. Food Processing and Xenobiotics
3. Effect of Food Processing-Borne Xenobiotics on the Gut Microbiota
3.1. Impact of Xenobiotics on Gut Microbiota
3.2. Impact of the Gut Microbiota on the Toxicity of Xenobiotics
4. Creating a Balance between Xenobiotics and a Healthy Gut
5. Future Perspectives
5.1. Probiotics and Prebiotics to Counteract the Effect of Pro-Carcinogenic Compounds
5.2. Longitudinal Studies on Long Term Impact of Xenobiotics Derived from Food Processing
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACs | Aminocarbolines |
AIAs | Aminoimidazoazarenes |
ATP | Adenosine triphosphate |
B(a)P | Benzo(a) pyrene |
CI | Confidence interval |
CRC | Colorectal cancer |
CYP1A1 | Aryl-4 monooxigenase |
CYP450 | Cytochrome P450 |
DiMeIQx | 2-Amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline |
EPIC | European Prospective Investigation into Cancer |
HCAs | Heterocyclic amines |
IARC | The International Agency for Research on Cancer |
LAB | Lactic acid bacteria |
MD | Mediterranean Diet |
MeIQ | 2-Amino-3,4-dimethylimidazo[4,5-f] quinoline |
MeIQx | 2-Amino-3,8-dimethylimidazo[4,5-f] quinoxaline |
MN | Micronucleous assay |
MTT | (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) |
NAs | Nitrosamines |
NOCs | N-Nitroso compounds |
OECD | Organization for Economic Cooperation and Development |
PAHs | Polycyclic aromatic hydrocarbons |
PhIP | 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine |
ROS | Reactive oxygen species |
RR | Relative risk |
SCE | Sister Chromatid Exchange assay |
SCFA | Short chain fatty acids |
WD | Western Diet |
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Year | No. Subjects | Analytical Category | Source | Dose | Pathology | Ref. |
---|---|---|---|---|---|---|
2018 | 407,270 | HCAs | Red meat | n.a a | MeIQx and DiMeIQx association with all anatomical subsites of colorectal cancer. PhIP associations with total colorectal and colon cancers. Not evidenced an association between ingested B(a)P and CRC | [46] |
MeIQx | ||||||
DiMeIQx | ||||||
PhIP | ||||||
PAHs | ||||||
B(a)P | ||||||
2018 | 76,657 | HCAs | Red meat | 50 ng/day | Association of HCAs, B(a)P, and mutagenicity index with the risk of colorectal adenomas | [47] |
MeIQx | n.a a | |||||
DiMeIQx | 40 ng/day | |||||
PhIP | n.a a | |||||
PAHs | ||||||
B(a)P | ||||||
2013 | total 3707: 1062 cases and 1645 controls | HCAs | Red meat | n.a a | Colon cancer | [48] |
MeIQx | ||||||
DiMeIQ | ||||||
PhIP |
Main Mechanism | Molecules/Compounds Involved | Microbial Group | Experimental Approach Used for Study | Mode of Action | Ref. | |
---|---|---|---|---|---|---|
Direct mechanisms | Genotoxins | Typhoid toxin | Salmonella enterica serovar Typhi | In vitro and animal models | DNAse activity; induction of symptoms characteristic of typhoid fever | [64] |
Cytolethal distending toxin | Proteobacteria | Cell lines and primary cell and mouse models of chronic infections | DNase activity; Proinflamation and carcinogenic potential | [65,66,67] | ||
Colibactin | Escherichia coli group B | Eukaryotic cells | DNA double-strand breaks | [68] | ||
Epidemiological and animal model | DNA double-strand breaks in vitro and in vivo; enhanced tumour growth by senescence | [69,70] | ||||
Alteration of host cellular cycle | Cytotoxin-associated gene A Vacuolating cytotoxin A | Helicobacter pylori | Molecular, experimental and epidemiological | DNA damage; Increases IL-8; produces reactive oxygen species (ROS) and nitric oxide; increases concentrations of cyclo-oxygenase 2; decreases apoptosis; and increases cell proliferation | [66,71] | |
Enterotoxin | Bacteroides fragilis | In vitro and epidemiological | DNA damage; high levels of ROS; Diarrheal disease, associated with colorectal cancer | [62,72] | ||
Adhesin A | Fusobacterium nucleatum | In vitro and epidemiological | Activation of β catenin pathway | [66,73] | ||
ExoS exotoxin | Pseudomonas aeruginosa | In vitro, experimental and epidemiological | Activation of pathways with final mechanism leading to DNA damage; unknown mechanisms in cancer generation | [62,66] | ||
Cysteine protease-like | Shigella flexneri | In vitro and epidemiological | Potassium outflow conducting to ROS production; induce degradation of p53; DNA damage; dysentery | [62,66] | ||
Avirulence protein A | Salmonella enterica | In vitro and mouse model of inflammation-associated cancer | Target β-catenin pathway; colonic tumorigenesis and tumour progression | [66] | ||
Cytotoxic necrotising factor | Escherichia coli | In vitro and animal models | Activates Rho GTPase; modifies cytoskeleton; triggers G1-S transition; downregulate mismatch repair genes; the role of CNF in infections in not clear | [71,74] | ||
Cycle-inhibiting factor | In vitro | Inhibition of mitosis | [75] | |||
Secondary bile acids | Anaerobic bacteria with 7-α dehydroxylation activity of primary bile acids | In vitro colon cells and animal models | Changes in physicochemical membrane properties; Apoptosis and genomic damage by ROS; Deoxycholic acid is carcinogenic at high doses and long-term treatment in animal models | [76] | ||
Indirect mechanisms | Oxidative stress | Reactive oxygen species | Peptostreptococcus anaerobius | In vivo, in vitro and epidemiological | Increase of human colon tumour tissues and adenomas; these bacteria increase colon dysplasia in a mouse model of CRC by induction of ROS levels, which promotes cholesterol synthesis and cell proliferation. | [77] |
Enterococcus faecalis | In vitro and in vivo models, epidemiological | Induction of ROS, activation of macrophages; promotion of tumorigenesis | [66,78] | |||
Faecal matrix | In vitro | Unknown reducing agent | [79] | |||
Formation of H2S | H2S | Sulfate-reducing bacteria | Epidemiological and in vitro models | Promotes instability or cumulative mutations in a predisposed genetic background | [80] | |
Inflammation | Wall-extracted antigen | Streptococcus bovis | Epidemiological and molecular | Activation of cyclo-oxygenase 2, interleukin 8 production, and cell proliferation | [71] | |
Disabling cellular DNA repair process | Listeriolysin O | Listeria monocytogenes | In vitro and epidemiological | Pore formation in intestinal host cells; Prevention of recruitment of repair complex to DNA breaks; listeriosis | [66] | |
Secreted effector protein EspF | Escherichia coli | In vitro | Down-regulation DNA mismatch repair | [66] | ||
Protein metabolism | Phenol/indol/p-cresol/ | Intestinal bacteria | Colonic cells | Increased anion superoxide production and genotoxic effects | [81,82] | |
Fecapentanes | Bacteroides sp. | In vitro; In vivo | Cytotoxic and mutagenic effects via ROS production; Controversial in vivo effect | [63,83] | ||
Ammonium | Intestinal bacteria | In vitro | Antiproliferative effect without decrease of cell viability | [84] |
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Nogacka, A.M.; Gómez-Martín, M.; Suárez, A.; González-Bernardo, O.; de los Reyes-Gavilán, C.G.; González, S. Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer. Int. J. Mol. Sci. 2019, 20, 2051. https://doi.org/10.3390/ijms20082051
Nogacka AM, Gómez-Martín M, Suárez A, González-Bernardo O, de los Reyes-Gavilán CG, González S. Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer. International Journal of Molecular Sciences. 2019; 20(8):2051. https://doi.org/10.3390/ijms20082051
Chicago/Turabian StyleNogacka, Alicja M., María Gómez-Martín, Adolfo Suárez, Oscar González-Bernardo, Clara G. de los Reyes-Gavilán, and Sonia González. 2019. "Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer" International Journal of Molecular Sciences 20, no. 8: 2051. https://doi.org/10.3390/ijms20082051
APA StyleNogacka, A. M., Gómez-Martín, M., Suárez, A., González-Bernardo, O., de los Reyes-Gavilán, C. G., & González, S. (2019). Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer. International Journal of Molecular Sciences, 20(8), 2051. https://doi.org/10.3390/ijms20082051