The role of the gut microbiota in colorectal cancer causation

Here, we reviewed emerging evidence on the role of the microbial community in colorectal carcinogenesis. A healthy gut microbiota promotes intestinal homeostasis and can exert anti-cancer effects; however, this microbiota also produces a variety of metabolites that are genotoxic and which can negatively influence epithelial cell behaviour. Disturbances in the normal microbial balance, known as dysbiosis, are frequently observed in colorectal cancer (CRC) patients. Microbial species linked to CRC include certain strains of , and amongst others. Whether these microbes are merely passive dwellers exploiting the tumour environment, or rather, active protagonists in the carcinogenic process is the subject of much research. The incidence of chemically-induced tumours in mice models varies, depending upon the presence or absence of these microorganisms, thus strongly suggesting influences on disease causation. Putative mechanistic explanations differentially link these strains to DNA damage, inflammation, aberrant cell behaviour and immune suppression. In the future, modulating the composition and metabolic activity of this microbial community may have a role in prevention and therapy

Consumption of a flavonoid-rich acai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men

Background: Acai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from acai consumption in humans is limited. Objective: The objective of the present study was to investigate the effect of acai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. Design: Twenty-three healthy male volunteers, aged 30–65 y and with a body mass index (in kg/m2) of 25–30, completed a randomized,controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an acai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). Results: The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with 20.3% for the PS (P , 0.001). There was also a significantly lower incremental area under the curve (iAUC)for total peroxide oxidative status after acai consumption relative to the control. No significant changes were observed in blood pressure,heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. Conclusions: In this acute study in overweight men, acai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of acai to health

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation

Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy

Ecosystem fluxes of hydrogen: a comparison of flux-gradient methods

Our understanding of biosphere–atmosphere exchange has been considerably enhanced by eddy covariance measurements. However, there remain many trace gases, such as molecular hydrogen (H[subscript 2]), that lack suitable analytical methods to measure their fluxes by eddy covariance. In such cases, flux-gradient methods can be used to calculate ecosystem-scale fluxes from vertical concentration gradients. The budget of atmospheric H[subscript 2] is poorly constrained by the limited available observations, and thus the ability to quantify and characterize the sources and sinks of H[subscript 2] by flux-gradient methods in various ecosystems is important. We developed an approach to make nonintrusive, automated measurements of ecosystem-scale H2 fluxes both above and below the forest canopy at the Harvard Forest in Petersham, Massachusetts, for over a year. We used three flux-gradient methods to calculate the fluxes: two similarity methods that do not rely on a micrometeorological determination of the eddy diffusivity, K, based on (1) trace gases or (2) sensible heat, and one flux-gradient method that (3) parameterizes K. We quantitatively assessed the flux-gradient methods using CO[subscript 2] and H[subscript 2]O by comparison to their simultaneous independent flux measurements via eddy covariance and soil chambers. All three flux-gradient methods performed well in certain locations, seasons, and times of day, and the best methods were trace gas similarity for above the canopy and K parameterization below it. Sensible heat similarity required several independent measurements, and the results were more variable, in part because those data were only available in the winter, when heat fluxes and temperature gradients were small and difficult to measure. Biases were often observed between flux-gradient methods and the independent flux measurements, and there was at least a 26% difference in nocturnal eddy-derived net ecosystem exchange (NEE) and chamber measurements. H[subscript 2] fluxes calculated in a summer period agreed within their uncertainty and pointed to soil uptake as the main driver of H[subscript 2] exchange at Harvard Forest, with H[subscript 2] deposition velocities ranging from 0.04 to 0.10 cm s[superscript −1].National Science Foundation (U.S.) (NSF Graduate Research Fellowship)United States. National Aeronautics and Space Administration (Advanced Global Atmospheric Gases Experiment (AGAGE))Massachusetts Institute of Technology. Joint Program on the Science & Policy of Global ChangeMartin Family Society of Fellows for SustainabilityMassachusetts Institute of Technology (Ally of Nature Research Fund)Massachusetts Institute of Technology (William Otis Crosby Lectureship)Massachusetts Institute of Technology (Warren Klein Fund

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

Iodine monoxide at a clean marine coastal site: observations of high frequency variations and inhomogeneous distributions

The first in situ point observations of iodine monoxide (IO) at a clean marine site were made using a laser-induced fluorescence instrument deployed at Mace Head, Ireland in August 2007. IO mixing ratios of up to 49.8 pptv (equivalent to pmol mol<sup>−1</sup>; 1 s average) were observed at day-time low tide, well in excess of previous observed spatially-averaged maxima. A strong anti-correlation of IO mixing ratios with tide height was evident and the high time resolution of the observations showed IO peaked in the hour after low tide. The temporal delay in peak IO compared to low tide has not been observed previously but coincides with the time of peak aerosol number previously observed at Mace Head. <br><br> A long path-differential optical absorption spectroscopy instrument (with a 2 × 6.8 km folded path across Roundstone Bay) was also based at the site for 3 days during the point measurement observation period. Both instruments show similar temporal trends but the point measurements of IO are a factor of ~6–10 times greater than the spatially averaged IO mixing ratios, providing direct empirical evidence of the presence of inhomogeneities in the IO mixing ratio near the intertidal region

The nutritional impact of replacing dietary meat with meat alternatives in the UK: a modelling analysis using nationally representative data

Dietary patterns high in meat compromise both planetary and human health. Meat-alternatives may help facilitate meat reduction, however the nutritional implications of displacing meat with meat-alternatives does not appear to have been evaluated. Here, data from the 9th cycle of the National Diet and Nutrition Survey was used as the basis of models to assess the effect of meat substitution on nutritional intake. We implemented three models; model 1 progressively replaced 25%, 50%, 75%, or 100% of the current meat intake with a weighted mean of meat-alternatives available in the UK market. Model 2 compared different ingredient categories of meat-alternative; vegetable, mycoprotein, a combination of bean and pea, tofu, nut and soy. Model 3 compared fortified versus unfortified meat-alternatives. The models elicited significant shifts in nutrients. Overall, there were increases in carbohydrate, fibre, sugars and sodium, whereas reductions were found for protein, total and saturated fat, iron and B12. The greatest effects were seen for; vegetable-based (+24.63g/day carbohydrates), mycoprotein-based (−6.12g/day total fat), nut-based (−19.79g/day protein, +10.23g/day fibre; −4.80g/day saturated fat, +7.44g/day sugars), soy-based (+495.98mg/day sodium), and tofu-based (+7.63mg/day iron, −2.02μg/day B12). Our results suggest meat-alternatives can be a healthful replacement for meat if chosen correctly. Consumers should seek out meat-alternatives which are low in sodium and sugar, high in fibre, protein and with high micronutrient density, to avoid compromising nutritional intake if reducing their meat intake. Manufacturers and policy makers should consider fortification of meat-alternatives with nutrients such as iron and B12 and focus on reducing sodium and sugar content

MYOD-1 in normal colonic mucosa : role as a putative biomarker?

Background DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Results We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development. Conclusions Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer