Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer

The colonic epithelium is exposed to a mixture of compounds through diet, among which some are procarcinogens, whereas others have a protective effect. Therefore, the net impact of these compounds on human health depends on the overall balance between all factors involved. Strong scientific evidence has demonstrated the relationship between nitrosamines (NA), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), which are the major genotoxins derived from cooking and food processing, and cancer. The mechanisms of the relationship between dietary toxic xenobiotics and cancer risk are not yet well understood, but it has been suggested that differences in dietary habits affect the colonic environment by increasing or decreasing the exposure to mutagens directly and indirectly through changes in the composition and activity of the gut microbiota. Several changes in the proportions of specific microbial groups have been proposed as risk factors for the development of neoplastic lesions and the enrichment of enterotoxigenic microbial strains in stool. In addition, changes in the gut microbiota composition and activity promoted by diet may modify the faecal genotoxicity/cytotoxicity, which can be associated with a higher or lower risk of developing cancer. Therefore, the interaction between dietary components and intestinal bacteria may be a modifiable factor for the development of colorectal cancer in humans and deserves more attention in the near future.

Download Full-text

The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome

Current Medicinal Chemistry ◽

10.2174/0929867324666170428103848 ◽

2019 ◽

Vol 26 (19) ◽

pp. 3567-3583 ◽

Cited By ~ 18

Author(s):

Maria De Angelis ◽

Gabriella Garruti ◽

Fabio Minervini ◽

Leonilde Bonfrate ◽

Piero Portincasa ◽

...

Keyword(s):

Gut Microbiota ◽

Human Health ◽

Dietary Habits ◽

Short Chain Fatty Acids ◽

Human Organism ◽

Immune Functions ◽

Intestinal Microbes ◽

Dietary Components ◽

Dietary Treatments ◽

The Relationship

Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influence the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota.

Download Full-text

Association of dietary fibre intake and gut microbiota in adults

British Journal Of Nutrition ◽

10.1017/s0007114518002465 ◽

2018 ◽

Vol 120 (9) ◽

pp. 1014-1022 ◽

Cited By ~ 20

Author(s):

Daniel Lin ◽

Brandilyn A. Peters ◽

Charles Friedlander ◽

Hal J. Freiman ◽

James J. Goedert ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Gut Microbiota ◽

Dietary Fibre ◽

Meta Analysis ◽

Microbiota Composition ◽

Fibre Intake ◽

Dietary Fibre Intake ◽

The Relationship ◽

Gut Microbiota Composition

AbstractIncreasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.

Download Full-text

Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21186782 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6782 ◽

Cited By ~ 2

Author(s):

Lidia Sánchez-Alcoholado ◽

Rafael Ordóñez ◽

Ana Otero ◽

Isaac Plaza-Andrade ◽

Aurora Laborda-Illanes ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Intestinal Bacteria ◽

Diagnostic Tools ◽

Opportunistic Pathogens ◽

Gut Permeability ◽

Microbial Profile ◽

Inflammatory Status ◽

Obesity And Cancer

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1β, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.

Download Full-text

The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7162545 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Tianqing Sang ◽

Wenli Qiu ◽

Wenting Li ◽

Hongli Zhou ◽

Haibin Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Clinical Practice ◽

Gut Microbiota ◽

Malignant Tumors ◽

Tumor Development ◽

Technological Advances ◽

Herbal Compound ◽

Chinese Herbal Compound ◽

The Relationship

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of “cancerous toxin” in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

Download Full-text

Nutrition and cancer: the current epidemiological evidence

British Journal Of Nutrition ◽

10.1079/bjn20061699 ◽

2006 ◽

Vol 96 (S1) ◽

pp. S42-S45 ◽

Cited By ~ 60

Author(s):

Carlos A. Gonzalez

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Colorectal Cancer ◽

Stomach Cancer ◽

Dietary Habits ◽

Scientific Evidence ◽

Glycaemic Index ◽

Overweight And Obesity ◽

Processed Meat ◽

Cancer Of The Lung

We have examined the current scientific evidence on the relationship between nutrition and the most frequent tumours in the Spanish population: lung, colorectal, prostate, breast and stomach. Consumption of fruit is negatively associated with cancer of the lung and stomach, possibly with colorectal cancer, but probably not with prostate cancer and breast cancer. Consumption of vegetables probably reduces the risk of colorectal and stomach cancer, but probably is not associated with cancer of the lung, prostate and breast. Consumption of red and processed meat is positively associated with colorectal cancer and probably with stomach cancer. Animal fat is possibly associated with colorectal cancer and probably with prostate and breast cancer. High alcohol intake increases the risk of colorectal and breast cancer, while dairy products and calcium seem to decrease the risk of colorectal cancer. Obesity is a recognised risk factor of colorectal cancer and breast cancer in postmenopausal women, while foods with a high glycaemic index and glycaemic load possibly increase the risk of colorectal and prostate cancer. The relevance of nutrition on the cancer process is evident. Nevertheless important issues remain to be solved and further studies are needed. This accumulative knowledge should be used by public health authorities to develop recommendations and activities to reduce overweight and obesity and to promote healthy dietary habits.

Download Full-text

Omega-3 PUFAs and gut microbiota: A preventive approach for colorectal cancer

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.2021.9954 ◽

2021 ◽

Author(s):

Marco Giammanco ◽

Margherita Mazzola ◽

Manfredi Marco Giammanco ◽

Giovanni Tomasello ◽

Francesco Carini

Keyword(s):

Colorectal Cancer ◽

Fatty Acids ◽

Inflammatory Response ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Bacteria ◽

Omega 3 ◽

Bacterial Composition ◽

Proinflammatory Mediators ◽

Strategic Approach

The influence of diet on the composition of the intestinal microbiota and related pathologies has been known for some time. Some classes of nutrients, such as fatty acids belonging to the omega 3 series, have particular effects on the bacteria that make up the intestinal microbiota. ω-3 PUFAs affect the gut microbiota in three different ways: by modulating the type and abundance of intestinal bacteria, by regulate SCFAs levels, and by alter the levels of proinflammatory mediators. Through these modalities, ω-3 PUFAs could be useful for the prevention of intestinal diseases such as colorectal cancer (CRC). The ability of ω-3 PUFAs to modulate the intestinal inflammatory response, to preserve the integrity of the intestinal mucosa and to modulate the bacterial composition of the intestine, could be useful as a preventive strategic approach to hinder the development of CRC.

Download Full-text

Association of dietary fiber intake and gut microbiota in healthy adults.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1569 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1569-1569 ◽

Cited By ~ 1

Author(s):

Daniel Lin ◽

Brandilyn Peters ◽

Rashmi Sinha ◽

James J. Goedert ◽

Richard Hayes ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Gut Microbiota ◽

Dietary Fiber ◽

Community Composition ◽

Meta Analysis ◽

Healthy Adults ◽

Fiber Intake ◽

Dietary Fiber Intake ◽

The Relationship

1569 Background: Increasing evidence has shown that gut microbiota alterations may play a role in colorectal cancer risk. Diet, particularly fiber intake, may modify gut microbiota composition, which may consequently impact cancer risk development. We investigated the relationship between dietary fiber intake and gut microbiota in healthy humans. Methods: Using 16S rRNA gene sequencing, we assessed gut microbiota in fecal samples from 151 healthy adults in two independent study populations: Study A, n = 75 (healthy controls from a colorectal cancer case-control study), and Study B, n = 76 (polyp-free subjects from a cross-sectional colonoscopy study). We calculated energy-adjusted total dietary fiber intake of participants based on food frequency questionnaires. For each study population, we evaluated the relationship between quartiles of higher fiber intake as a continuous ordinal variable, and global gut microbiota community composition (via PERMANOVA of weighted UniFrac distance) and specific taxon abundance (via DESeq2). Results: We found that fiber intake was significantly associated with overall microbial community composition in Study B (p = 0.003) but not Study A (p = 0.68), after adjustment for age, sex, race, body mass index, and cigarette smoking. In a taxonomy-based meta-analysis of these two study populations, higher fiber intake was associated with lower abundance of genus Actinomyces (fold change [FC] = 0.769, p = 0.003), and higher abundance of genera Faecalibacterium (FC = 1.153, p = 0.03), Lachnospira (FC = 1.167, p = 0.04), and SMB53 (FC = 1.201, p = 0.05). A species-level meta-analysis showed an association between higher fiber intake and higher abundance of Faecalibacterium prausnitzii (FC = 1.165, p = 0.03) and lower abundance of Ruminococcus bromii (FC = 0.828, p = 0.08). Conclusions: Our results suggest that higher intake of dietary fiber may alter gut microbiota in healthy adults. Given the potentially modifiable nature of the gut microbiota through diet, these findings warrant further study of diet-microbiota based colorectal cancer prevention strategies.

Download Full-text

Insights Into the Relationship Between Gut Microbiota and Colorectal Cancer

Current Colorectal Cancer Reports ◽

10.1007/s11888-018-0419-4 ◽

2018 ◽

Vol 14 (6) ◽

pp. 251-265 ◽

Cited By ~ 1

Author(s):

João Felipe Mota ◽

Jens Walter ◽

Carla M. Prado

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

The Relationship

Download Full-text

Genetic Polymorphisms of Vitamin D Receptor (VDR), CYP27B1 and CYP24A1 Genes and the Risk of Colorectal Cancer

The International Journal of Biological Markers ◽

10.5301/jbm.5000248 ◽

2017 ◽

Vol 32 (2) ◽

pp. 224-230 ◽

Cited By ~ 15

Author(s):

Verônica Marques Vidigal ◽

Tiago Donizetti Silva ◽

Juliana de Oliveira ◽

Célia Aparecida Marques Pimenta ◽

Aledson Vitor Felipe ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Vitamin D Receptor ◽

Dairy Products ◽

Dietary Habits ◽

Heterozygous Genotype ◽

Increased Risk ◽

Pcr Rflp ◽

Apai Polymorphism ◽

The Relationship

Introduction Vitamin D receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 involved in the production and inactivation of vitamin D can influence vitamin D and the susceptibility to colorectal cancer (CRC). The objective of this study was to investigate the relationship between the risk of CRC and polymorphisms in VDR, CYP27B1 and CYP24A1, lifestyle and dietary habits. Methods The study included 152 patients with CRC and 321 controls. All participants answered a questionnaire on their dietary habits, alcohol consumption and smoking habits. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by performing PCR-RFLP. Identification of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) polymorphisms was performed by gene sequencing. Results Smoking, alcohol use, and low or no consumption of fruit, cereals and dairy products were associated with an increased risk of CRC. A heterozygous genotype Aa or an association genotype aa + Aa of the VDR ApaI polymorphism increased the risk of CRC. The VDR BsmI polymorphism was not significantly associated with the risk of CRC. Multivariate analysis showed that heterozygous and association genotype AT + AA of the rs6013897 polymorphism, genotype CT of the rs158552 polymorphism, association genotype CT + CC and genotypes AA and GG of the rs17217119 polymorphism of CYP24A1, and heterozygous genotype GT and association genotype GT + TT of the rs10877012 polymorphism in CYP27B1 were associated with a higher risk of CRC. Conclusions Dietary habits, lifestyle, and polymorphisms in VDR (ApaI), CYP24A1 (rs6013897, rs158552, rs17217119) and CYP27B1 (rs10877012) were associated with a higher risk of CRC.

Download Full-text