Dietary Nitrosamines from Processed Meat Intake as Drivers of the Fecal Excretion of Nitrosocompounds.

Diet is one of the main exogenous sources of potentially carcinogenic nitrosamines (NAs) along with tobacco and cosmetics. Several factors can affect endogenous N-nitroso compounds (NOCs) formation and therefore the potential damage of the intestinal mucosa at initial colorectal cancer stages. To address this issue, 49 volunteers were recruited and classified according to histopathological analyses. Lifestyle and dietary information were registered after colonoscopy. The mutagenicity of fecal supernatants was assayed by a modified Ames test. Fecal heme-derived NOCs and total NOC concentrations were determined by selective denitrosation and chemiluminescence-based detection. Results revealed processed meats as the main source of dietary nitrites and NAs, identifying some of them as predictors of the fecal concentration of heme-derived and total NOCs. Furthermore, increased fecal NOC concentrations were found as the severity of colonic mucosal damage increased from the control to the adenocarcinoma group, these concentrations being strongly correlated with the intake of the NAs N-nitrosodimethylamine, N-nitrosopiperidine, and N-nitrosopyrrolidine. Higher fecal NOC concentrations were also noted in higher fecal mutagenicity samples. These results could contribute to a better understanding of the importance of modulating dietary derived xenobiotics as related with their impact on the intestinal environment and colonic mucosa damage.

Human fecal alpha-glucosidase activity and its relationship with gut microbiota profiles and early stages of intestinal mucosa damage.

OBJECTIVES: We investigated potential relationships among initial lesions of the intestinal mucosa, fecal enzymatic activities and microbiota profiles. METHODS: Fecal samples from 54 volunteers were collected after recruitment among individuals participating in a colorectal cancer (CRC) screening program in our region (Northern Spain) or attending for consultation due to clinical symptoms; intestinal mucosa samples were resected during colonoscopy. Enzymatic activities were determined in fecal supernatants by a semi-quantitative method. The fecal microbiota composition was determined by 16S rRNA gene-based sequencing. The results were compared between samples from clinical diagnosis groups (controls and polyps), according with the type of polyp (hyperplastic polyps or conventional adenomas) and considering the grade of dysplasia for conventional adenomas (low and high grade dysplasia). RESULTS: High levels of α-glucosidase activity were more frequent among samples from individuals diagnosed with intestinal polyps, reaching statistical significance for conventional adenomas and for low grade dysplasia adenomas when compared to controls. Regarding the microbiota profiles, higher abundance of Christensenellaceae_R-7 group and Oscillospiraceae_UCG-002 were found in fecal samples displaying low α-glucosidase activity as compared with those with higher activity as well as in controls with respect to conventional adenomas. A relationship was evidenced among intestinal mucosal lesions, gut glucosidase activities and intestinal microbiota profiles. CONCLUSIONS: Our findings suggest a relationship among altered fecal α-glucosidase levels, the presence of intestinal mucosal lesions, which can be precursors of CRC, and shifts in defined microbial groups of the fecal microbiota.

Role of the intestinal microbiota and diet in the onset and progression of colorectal and breast cancers and the interconnection between both types of tumours.

Colorectal cancer (CRC) is among the leading causes of mortality in adults of both sexes worldwide, while breast cancer (BC) is among the leading causes of death in women. In addition to age, gender, and genetic predisposition, environmental and lifestyle factors exert a strong influence. Global diet, including alcohol consumption, is one of the most important modifiable factors affecting the risk of CRC and BC. Western dietary patterns promoting high intakes of xenobiotics from food processing and ethanol have been associated with increased cancer risk, whereas the Mediterranean diet, generally leading to a higher intake of polyphenols and fibre, has been associated with a protective effect. Gut dysbiosis is a common feature in CRC, where the usual microbiota is progressively replaced by opportunistic pathogens and the gut metabolome is altered. The relationship between microbiota and BC has been less studied. The estrobolome is the collection of genes from intestinal bacteria that can metabolize oestrogens. In a dysbiosis condition, microbial deconjugating enzymes can reactivate conjugated-deactivated oestrogens, increasing the risk of BC. In contrast, intestinal microorganisms can increase the biological activity and bioavailability of dietary phytochemicals through diverse microbial metabolic transformations, potentiating their anticancer activity. Members of the intestinal microbiota can increase the toxicity of xenobiotics through metabolic transformations. However, most of the microorganisms involved in diet-microbiota interactions remain poorly characterized. Here, we provide an overview of the associations between microbiota and diet in BC and CRC, considering the diverse types and heterogeneity of these cancers and their relationship between them and with gut microbiota.

Immunometabolic Profile Associated with Progressive Damage of the Intestinal Mucosa in Adults Screened for Colorectal Cancer: Association with Diet.

Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC.

Associations of dietary factors and xenobiotic intake with faecal microbiota composition according to the presence of intestinal mucosa damage.

Diet is a major modulator of gut microbiota, which plays a key role in the health status, including colorectal cancer (CRC) development. Several studies and meta-analyses have evidenced an association of certain dietary factors and xenobiotic intake with the incidence of CRC. Nevertheless, how these dietary factors impact the first stages of intestinal mucosa damage is still uncertain. This study aimed at exploring the associations of relevant dietary factors with the gut microbiota of control individuals and subjects diagnosed with intestinal polyps. A total of 60 volunteers were recruited, clinically classified according to colonoscopy criteria and interviewed using food frequency questionnaires (FFQs). The nutritional status of each volunteer was determined and the intake of dietary xenobiotics was quantified. The relative abundance of faecal microbiota taxonomic groups was obtained through 16S rRNA gene sequencing. The association of dietary factors and xenobiotics with faecal microbiota composition showed differences according to the clinical diagnosis group. Our results showed that the intake of red meat (≥50 g day-1) and total polycyclic aromatic hydrocarbons (PAHs) (≥0.75 µg day-1) was associated with a decreased abundance of the family Bacteroidaceae and an increased abundance of Coriobacteriaceae in control subjects. The intake of the heterocyclic amines 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (≥40 ng day-1) and 2-amino-3,8 dimethylimidazo(4,5,f) quinoxaline (MeIQx) (≥50 ng day-1) was associated with a decreased abundance of Akkermansiaceae in the control diagnosis group. Moreover, N-nitroso compounds (NOCs), nitrites (≥1.69 mg day-1) and N-nitrosodimethylamine (NDMA) (≥0.126 µg day-1) were associated with a decreased abundance of Bifidobacteriaceae. The intake of ethanol (≥12 g day-1) in the polyps group was associated with an increased abundance of Peptostreptococcaceae and a decreased abundance of Veillonellaceae. Moreover, linear regression analyses allowed us to identify ethanol, calcium, bioactive compounds such as flavonoids, stilbenes, cellulose, phenolic acids or total polyphenols, and dietary xenobiotics such as PhIP and MeIQx, the NOC N-nitrosopyrrolidine (NPYR) or the total PAHs as potential predictors of faecal microbiota group abundances. These results indicated that the consumption of milk, red meat, processed meat and ethanol and the intake of polyphenols, dietary PAHs, HAs and NOCs are associated with specific groups of the intestinal microbiota, depending on the clinical diagnosis group.

Impact on Fecal Microbiota and Health-Related Markers of an Intervention Focused on Improving Eating Behavior in People at Risk of Food Insecurity.

Non-communicable diseases are particularly prevalent among low-income individuals and are associated with the consumption of processed foods, fat, and sugars. This work aims to evaluate the impacts of a nutrition education intervention for low socio-economic individuals on sensory perception, health-related parameters and gut microbiota. Twenty low-income adults underwent a 4-week intervention. Dietary information (three 24 h recalls), detection thresholds and discrimination scores (salty and sweet), and severity of depressive symptoms (Beck Depression Inventory-II (BDI-II)) were collected. Fecal microbial composition and short chain fatty acids were determined by 16S ribosomal RNA-gene sequencing and gas chromatography, respectively. After the intervention, 35% of subjects presented higher compliance with dietary recommendations, increased consumption of vegetables and lignans and reduced consumption of processed meats and nitrosamines, together with depleted levels of Actinomycetota. Higher discrimination for salty and sweet and lower BDI-II scores were also obtained. This nutrition education intervention entailed changes in dietary intake towards healthier food options, reduced potentially carcinogenic compounds and improved scores for discrimination and severity of depressive symptoms. The confirmation of these results in future studies would enable the design of strategic policies contributing to the optimal nutrition of materially deprived families through affordable healthy plant-based interventions.

Commensal Fecal Microbiota Profiles Associated with Initial Stages of Intestinal Mucosa Damage: A Pilot Study.

Progressive intestinal mucosal damage occurs over years prior to colorectal cancer (CRC) development. The endoscopic screening of polyps and histopathological examination are used clinically to determine the risk and progression of mucosal lesions. We analyzed fecal microbiota compositions using 16S rRNA gene-based metataxonomic analyses and the levels of short-chain fatty acids (SCFAs) using gas chromatography in volunteers undergoing colonoscopy and histopathological analyses to determine the microbiota shifts occurring at the early stages of intestinal mucosa alterations. The results were compared between diagnosis groups (nonpathological controls and polyps), between samples from individuals with hyperplastic polyps or conventional adenomas, and between grades of dysplasia in conventional adenomas. Some microbial taxa from the Bacillota and Euryarchaeota phyla were the most affected when comparing the diagnosis and histopathological groups. Deeper microbiota alterations were found in the conventional adenomas than in the hyperplastic polyps. The Ruminococcus torques group was enriched in both the hyperplastic polyps and conventional adenomas, whereas the family Eggerthellaceae was enriched only in the hyperplastic polyps. The abundance of Prevotellaceae, Oscillospiraceae, Methanobacteriaceae, Streptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Clostridiaceae shifted in conventional adenomas depending on the grade of dysplasia, without affecting the major SCFAs. Our results suggest a reorganization of microbial consortia involved in gut fermentative processes.

Dietary xenobiotics, (poly)phenols and fibers: Exploring associations with gut microbiota in socially vulnerable individuals.

Objectives: Although xenobiotics derived from food processing may cause modifications in the composition of the gut microbiota (GM) evidence is scarce. The aim of this study is to evaluate the impact of potential dietary carcinogens as heterocyclic amines (HAs), polycyclic aromatic hydrocarbons (PAHs), nitrates, nitrites, nitroso compounds and acrylamide, in combination to fibers (poly)phenols on the GM composition in a group of materially deprived subjects. Study design: Transversal observational study in a sample of 19 subjects recipients of Red Cross food aid. Dietary information was recorded by means of 3 non-consecutive 24 h recalls. Questions focused on the type of cooking and the extent of cooking and roasting were included. Information on potential carcinogens was mainly obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) and Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) Carcinogen Databases. Microbial composition was determined by 16S ribosomal RNA gene sequencing in fecal samples. Results: Higher levels of Lachnospiraceae and Eggerthellaceae families were found in individuals consuming less than 50 ng/day of 2-amino-3,8 dimethylimidazo (4,5,f) quinoxaline (MeIQx) (considered as lower risk dose for colorectal adenoma) while those consuming more than 40 ng/day of 2-amino-1-methyl-6-phenylimidazo (4,5,b) pyridine (PhIP) (higher risk for colorectal adenoma) showed lower relative abundance of Muribaculaceae and greater presence of Streptococcaceae and Eubacterium coprostanoligenes group. Conclusion: The associations identified between diet and processing by-products on GM in this study could be used as potential targets for the designing of dietary interventions tailored to this collective.

Dietary Xenobiotics Derived from Food Processing: Association with Fecal Mutagenicity and Gut Mucosal Damage.

Whereas the mechanisms underlying the association of toxic dietary xenobiotics and cancer risk are not well established, it is plausible that dietary pattern may affect the colon environment by enhancing or reducing exposure to mutagens. This work aimed to investigate the association between xenobiotics intake and different stages of intestinal mucosal damage and colorectal cancer (CRC) screening and examine whether these associations may be mediated by altered intestinal mutagenicity. This was a case control study with 37 control subjects, 49 patients diagnosed with intestinal polyps, and 7 diagnosed with CRC. Lifestyle, dietary, and clinical information was registered after colonoscopy. For xenobiotics intake estimation the European Prospective Investigation into Cancer (EPIC) and the Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) databases were used. The mutagenicity of fecal supernatants was assayed by the Ames test and light microscopy was used for the presence of aberrant crypt formation. Among all the potential carcinogens studied, the polyp group showed higher intakes of ethanol and dibenzo (a) anthracene (DiB(a)A). Besides, intakes between 0.75 and 1.29 µg/d of total polycyclic aromatic hydrocarbons (PAHs) were related with a higher risk of belonging to the polyp group. On the contrary, an intake of wholegrain cereals greater than 50 g/d was associated with a reduction in the relative risk of belonging to the polyp group. Heterocyclic amines (HAs) such as 2-amino-1-methyl-6-phenylimidazo (4,5,b) pyridine (PhIP) were associated with an increased level of mutagenicity in polyps. This study is of great interest for the identification of possible therapeutic targets for the early prevention of colon cancer through diet.

Pilot Study for the Dietary Assessment of Xenobiotics Derived from Food Processing in an Adult Spanish Sample.

BACKGROUND: Although xenobiotics from food processing have gained support as possible drivers of the relationship between diet and some types of cancer, there are still few studies characterizing the intake of these compounds among different populations. AIM: To describe the intake of heterocyclic amines (HAs), polycyclic aromatic hydrocarbons (PAHs), nitrates, nitrites, nitrosamines, and acrylamide; and to identify dietary and lifestyle related factors. METHODS: This was a descriptive cross-sectional study in 70 adult volunteers. Intake was registered by means of a food frequency questionnaire, including cooking methods, temperature, and degree of browning. The European Prospective Investigation into Cancer (EPIC) and the Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) databases were used for xenobiotic estimation in conjunction with data from the European Food Safety Authority (EFSA) and U.S. Food and Drug Administration (FDA). RESULTS: Dietary HAs (amino-alpha-carboline (AαC), 2-amino-3-methylimidazo (4,5,f) quinoline (IQ), 2-amino-3,8 dimethylimidazo (4,5,f) quinoxaline (MeIQx), 2-amino-3,4,8 trime-thylimidazo (4,5,f) quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo (4,5,b) pyridine (PhIP)) were mainly derived from meat and meat products, while benzo (a) pyrene (B(a)P), dibenzo (a) anthracene (DiB(a)A), and total PAHs were explained by oils and fats, alcoholic beverages, and milk, respectively. Microwaved, fried, grilled, broiled, barbecued, and braised cooking methods were mainly responsible for HAs and PAHs consumption. CONCLUSION: Based on the wide presence and levels of intake of these compounds in different sources, more efforts should be made to adjust their intake to the levels recommended by health agencies.

Intestinal microbiota alterations by dietary exposure to chemicals from food cooking and processing. Application of data science for risk prediction.

Diet is one of the main sources of exposure to toxic chemicals with carcinogenic potential, some of which are generated during food processing, depending on the type of food (primarily meat, fish, bread and potatoes), cooking methods and temperature. Although demonstrated in animal models at high doses, an unequivocal link between dietary exposure to these compounds with disease has not been proven in humans. A major difficulty in assessing the actual intake of these toxic compounds is the lack of standardised and harmonised protocols for collecting and analysing dietary information. The intestinal microbiota (IM) has a great influence on health and is altered in some diseases such as colorectal cancer (CRC). Diet influences the composition and activity of the IM, and the net exposure to genotoxicity of potential dietary carcinogens in the gut depends on the interaction among these compounds, IM and diet. This review analyses critically the difficulties and challenges in the study of interactions among these three actors on the onset of CRC. Machine Learning (ML) of data obtained in subclinical and precancerous stages would help to establish risk thresholds for the intake of toxic compounds generated during food processing as related to diet and IM profiles, whereas Semantic Web could improve data accessibility and usability from different studies, as well as helping to elucidate novel interactions among those chemicals, IM and diet.

Comparison of Different Dietary Indices as Predictors of Inflammation, Oxidative Stress and Intestinal Microbiota in Middle-Aged and Elderly Subjects.

During the last decades the gut microbiota has been identified as a key mediator in the diet-health interaction. However, our understanding on the impact of general diet upon microbiota is still limited. Dietary indices represent an essential approach for addressing the link between diet and health from a holistic point of view. Our aim was to test the predictive potential of seven dietary ratings on biomarkers of inflammation, oxidative stress and on the composition and metabolic activity of the intestinal microbiota. A cross-sectional descriptive study was conducted on a sample of 73 subjects aged >50 years with non-declared pathologies. Dietary inflammatory index (DII), Empirical Dietary Inflammatory Index (EDII), Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), Mediterranean adapted Diet Quality Index-International (DQI-I), Modified Mediterranean Diet Score (MMDS) and relative Mediterranean Diet Score (rMED) were calculated based on a Food Frequency Questionnaire. Major phylogenetic types of the intestinal microbiota were determined by real time polymerase chain reaction (qPCR) and fecal short chain fatty acids (SCFAs) by gas chromatography. While DII, HEI, DQI-I and MMDS were identified as predictors of Faecalibacterium prausnitzii levels, AHEI and MMDS were negatively associated with Lactobacillus group. HEI, AHEI and MMDS were positively associated with fecal SCFAs. In addition, DII and EDII explained lipoperoxidation level and Mediterranean scores the serum IL-8 concentrations. The lower detection of IL-8 in individuals with higher scores on Mediterranean indices may be partially explained by the increased levels of the anti-inflammatory bacterium F. prausnitzii in such individuals.

Long-Term Coffee Consumption is Associated with Fecal Microbial Composition in Humans.

Coffee consumption has been related to a preventive effect against several non-transmissible pathologies. Due to the content of this beverage in phytochemicals and minerals, it has been proposed that its impact on health may partly depend on gut microbiota modulation. Our aim was to explore the interaction among gut microbiota, fecal short chain fatty acids, and health-related parameters in 147 healthy subjects classified according to coffee consumption, to deepen the association of the role of the (poly)phenol and alkaloid content of this beverage. Food daily intake was assessed by an annual food frequency questionnaire (FFQ). Coffee consumption was categorized into three groups: non-coffee-consumers (0-3 mL/day), moderate consumers (3-45 mL/day) and high-coffee consumers (45-500 mL/day). Some relevant groups of the gut microbiota were determined by qPCR, and concentration of fecal short chain fatty acids by gas chromatography. Serum health related biomarkers were determined by standardized methods. Interestingly, a higher level of Bacteroides-Prevotella-Porphyromonas was observed in the high consumers of coffee, who also had lower levels of lipoperoxidation. Two groups of coffee-derived (poly)phenol, methoxyphenols and alkylphenols, and caffeine, among alkaloids, were directly associated with Bacteroides group levels. Thus, regular consumption of coffee appears to be associated with changes in some intestinal microbiota groups in which dietary (poly)phenol and caffeine may play a role.