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

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

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

Modelling the role of microbial p-cresol in colorectal genotoxicity

BACKGROUND A greater understanding of mechanisms explaining the interactions between diet and the gut microbiota in colorectal cancer is desirable. Genotoxic microbial metabolites present in the colon may be implicated in carcinogenesis and potentially influenced by diet. AIMS We hypothesised that microbial p-cresol is a colonic genotoxin and set out to model potential exposures in the colon and the effects of these exposures on colonic cells. METHODS Batch culture fermentations with human faecal inoculate were used to determine the synthesis of p-cresol and other metabolites in response to various substrates. The fermentation supernatants were evaluated for genotoxicity and the independent effects of p-cresol on colonic cells were studied in vitro. RESULTS In batch culture fermentation, supplementary protein increased the synthesis of phenols, indoles and p-cresol, whereas supplementary fructoligosaccharide (FOS) increased the synthesis of short chain fatty acids. The p-cresol was the greatest predictor of genotoxicity against colonocytes in the fermentation supernatants. Spiking fermentation supernatants with exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics. CONCLUSIONS In the colon p-cresol may reach physiologically significant concentrations which contribute to genotoxic exposures in the intestinal lumen, p-cresol production may be attenuated by substrate, and therefore diet, making it a potential modifiable biomarker of genotoxicity in the colon

Atmospheric Acetaldehyde: Importance of Air-Sea Exchange and a Missing Source in the Remote Troposphere.

We report airborne measurements of acetaldehyde (CH3CHO) during the first and second deployments of the National Aeronautics and Space Administration (NASA) Atmospheric Tomography Mission (ATom). The budget of CH3CHO is examined using the Community Atmospheric Model with chemistry (CAM-chem), with a newly-developed online air-sea exchange module. The upper limit of the global ocean net emission of CH3CHO is estimated to be 34 Tg a-1 (42 Tg a-1 if considering bubble-mediated transfer), and the ocean impacts on tropospheric CH3CHO are mostly confined to the marine boundary layer. Our analysis suggests that there is an unaccounted CH3CHO source in the remote troposphere and that organic aerosols can only provide a fraction of this missing source. We propose that peroxyacetic acid (PAA) is an ideal indicator of the rapid CH3CHO production in the remote troposphere. The higher-than-expected CH3CHO measurements represent a missing sink of hydroxyl radicals (and halogen radical) in current chemistry-climate models

Impact of dietary supplementation with resistant dextrin (NUTRIOSE®) on satiety, glycaemia, and related endpoints, in healthy adults

Purpose Resistant dextrin (RD) supplementation has been shown to alter satiety, glycaemia, and body weight, in overweight Chinese men; however, there are limited data on its effects in other demographic groups. Here, we investigated the effects of RD on satiety in healthy adults living in the United Kingdom. Methods 20 normal weight and 16 overweight adults completed this randomised controlled cross-over study. Either RD (14 g/day NUTRIOSE® FB06) or maltodextrin control was consumed in mid-morning and mid-afternoon preload beverages over a 28-day treatment period with crossover after a 28-day washout. During 10-h study visits (on days 1, 14, and 28 of each treatment period), satietogenic, glycaemic and anorectic hormonal responses to provided meals were assessed. Results Chronic supplementation with RD was associated with higher fasted satiety scores at day 14 (P = 0.006) and day 28 (P = 0.040), compared to control. RD also increased satiety after the mid-morning intervention drink, but it was associated with a reduction in post-meal satiety following both the lunch and evening meals (P < 0.01). The glycaemic response to the mid-morning intervention drink (0–30 min) was attenuated following RD supplementation (P < 0.01). Whilst not a primary endpoint we also observed lower systolic blood pressure at day 14 (P = 0.035) and 28 (P = 0.030), compared to day 1, following RD supplementation in the normal weight group. Energy intake and anthropometrics were unaffected. Conclusions RD supplementation modified satiety and glycaemic responses in this cohort, further studies are required to determine longer-term effects on body weight control and metabolic markers

In vitro approaches to assess the effects of açai (Euterpe oleracea) digestion on polyphenol availability and the subsequent impact on the faecal microbiota

A considerable proportion of dietary plant-polyphenols reach the colon intact; determining the effects of these compounds on colon-health is of interest. We hypothesise that both fibre and plant polyphenols present in açai (Euterpe oleracea) provide prebiotic and anti-genotoxic benefits in the colon. We investigated this hypothesis using a simulated in vitro gastrointestinal digestion of açai pulp, and a subsequent pH-controlled, anaerobic, batch-culture fermentation model reflective of the distal region of the human large intestine. Following in vitro digestion, 49.8% of the total initial polyphenols were available. In mixed-culture fermentations with faecal inoculate, the digested açai pulp precipitated reductions in the numbers of both the Bacteroides-Prevotella spp. and the Clostridium-histolyticum groups, and increased the short-chain fatty acids produced compared to the negative control. The samples retained significant anti-oxidant and anti-genotoxic potential through digestion and fermentation. Dietary intervention studies are needed to prove that consuming açai is beneficial to gut health

Corrigendum to "Overview: oxidant and particle photochemical processes above a south-east Asian tropical rainforest (the OP3 project): introduction, rationale, location characteristics and tools" published in Atmos. Chem. Phys., 10, 169–199, 2010

Author(s): Hewitt, CN; Lee, JD; MacKenzie, AR; Barkley, MP; Carslaw, N; Carver, GD; Chappell, NA; Coe, H; Collier, C; Commane, R; Davies, F; Davison, B; DiCarlo, P; Di Marco, CF; Dorsey, JR; Edwards, PM; Evans, MJ; Fowler, D; Furneaux, KL; Gallagher, M; Guenther, A; Heard, DE; Helfter, C; Hopkins, J; Ingham, T; Irwin, M; Jones, C; Karunaharan, A; Langford, B; Lewis, AC; Lim, SF; MacDonald, SM; Mahajan, AS; Malpass, S; McFiggans, G; Mills, G; Misztal, P; Moller, S; Monks, PS; Nemitz, E; Nicolas-Perea, V; Oetjen, H; Oram, DE; Palmer, PI; Phillips, GJ; Pike, R; Plane, JMC; Pugh, T; Pyle, JA; Reeves, CE; Robinson, NH; Stewart, D; Stone, D; Whalley, LK; Yang,

Cross-feeding interactions between human gut commensals belonging to the Bacteroides and Bifidobacterium genera when grown on dietary glycans

Elements of the human gut microbiota metabolise many host- and diet-derived, non-digestible carbohydrates (NDCs). Intestinal fermentation of NDCs salvages energy and resources for the host and generates beneficial metabolites, such as short chain fatty acids, which contribute to host health. The development of functional NDCs that support the growth and/or metabolic activity of specific beneficial gut bacteria, is desirable, but dependent on an in-depth understanding of the pathways of carbohydrate fermentation. The purpose of this review is to provide an appraisal of what is known about the roles of, and interactions between, Bacteroides and Bifidobacterium as key members involved in NDC utilisation. Bacteroides is considered an important primary degrader of complex NDCs, thereby generating oligosaccharides, which in turn can be fermented by secondary degraders. In this review, we will therefore focus on Bacteroides as an NDC-degrading specialist and Bifidobacterium as an important and purported probiotic representative of secondary degraders. We will describe cross-feeding interactions between members of these two genera. We note that there are limited studies exploring the interactions between Bacteroides and Bifidobacterium, specifically concerning β-glucan and arabinoxylan metabolism. This review therefore summarises the roles of these organisms in the breakdown of dietary fibre and the molecular mechanisms and interactions involved. Finally, it also highlights the need for further research into the phenomenon of cross-feeding between these organisms for an improved understanding of these cross-feeding mechanisms to guide the rational development of prebiotics to support host health or to prevent or combat disease associated with microbial dysbiosis