The high-meat, low-fibre Western diet is strongly associated with colorectal cancer risk. Mycoprotein, produced from Fusarium venanatum, has been sold as a high-fibre alternative to meat for decades. Hitherto, the effects of mycoprotein in the human bowel have not been well considered. Here, we explored the effects of replacing a high red and processed meat intake with mycoprotein on markers of intestinal genotoxicity and gut health. Mycomeat (clinicaltrials.gov NCT03944421) was an investigator-blind, randomised, crossover dietary intervention trial. Twenty healthy male adults were randomised to consume 240 g day−1 red and processed meat for 2 weeks, with crossover to 2 weeks 240 g day−1 mycoprotein, separated by a 4-week washout period. Primary end points were faecal genotoxicity and genotoxins, while secondary end points comprised changes in gut microbiome composition and activity. The meat diet increased faecal genotoxicity and nitroso compound excretion, whereas the weight-matched consumption of mycoprotein decreased faecal genotoxicity and nitroso compounds. In addition, meat intake increased the abundance of Oscillobacter and Alistipes, whereas mycoprotein consumption increased Lactobacilli, Roseburia and Akkermansia, as well as the excretion of short chain fatty acids. Replacing red and processed meat with the Fusarium-based meat alternative, mycoprotein, significantly reduces faecal genotoxicity and genotoxin excretion and increases the abundance of microbial genera with putative health benefits in the gut. This work demonstrates that mycoprotein may be a beneficial alternative to meat within the context of gut health and colorectal cancer prevention.
PurposePrebiotic foods can be used to increase production of short-chain fatty acids (SCFA) in the gut. Of the SCFA, propionate is credited with the strongest anorectic activity. In previous work, a 50/50 blend of inulin and arabinoxylan was produced (I + AX) that significantly increased propionate production in an in vitro gut model. This study sought to establish whether chronic consumption of a prebiotic blend of I + AX decreases appetite and energy intake and increases intestinal propionate production in human participants.MethodsMIXSAT (clinicaltrials.gov id: NCT02846454, August 2016) was a double-blind randomised acute-within-chronic crossover feeding trial in healthy adult men (n = 20). Treatments were 8 g per day I + AX for 21 days or weight-matched maltodextrin control. The primary outcome measure was perceived satiety and appetite during an acute study visit. Secondary outcomes were energy intake in an ad libitum meal, faecal SCFA concentration, and faecal microbiota composition.ResultsPerceived satiety and appetite were not affected by the intervention. I + AX was associated with a reduction in energy intake in an ad libitum meal, increased faecal SCFA concentration, and an increase in cell counts of Bifidobacteria, Lactobacilli, and other microbial genera associated with health.ImplicationsChronic consumption of this blend of prebiotics decreased energy intake in a single sitting. Further studies are needed to confirm mechanism of action and to determine whether this might be useful in weight control.
Purpose Mycoprotein is a relatively novel food source produced from the biomass of Fusarium venenatum . It has previously been shown to improve CVD risk markers in intervention trials when it is compared against total meat. It has not hitherto been assessed specifically for benefits relative to red and processed meat. Methods We leveraged samples from Mycomeat, an investigator-blind randomised crossover controlled trial in metabolically healthy male adults (n = 20), randomised to consume 240 g/day of red and processed meat for 14 days followed by mycoprotein, or vice versa. Blood biochemical indices were a priori defined secondary endpoints. Results Mycoprotein consumption led to a 6.74% reduction in total cholesterol ( P = 0.02) and 12.3% reduction in LDL cholesterol ( P = 0.02) from baseline values. Change in fasted triglycerides was not significantly different between diets (+ 0.19 ± 0.11 mmol/l with mycoprotein, P = 0.09). There was a small but significant reduction in waist circumference for mycoprotein relative to meat (− 0.95 ± 0.42 cm, P = 0.04). Following the mycoprotein diet, mean systolic (− 2.41 ± 1.89 mmHg, P = 0.23) and diastolic blood pressure (− 0.80 ± 1.23 mmHg, P = 0.43) were reduced from baseline. There were no statistically significant effects of the intervention on urinary sodium, nitrite or TMAO; while urinary potassium (+ 126.12 ± 50.30 mmol/l, P = 0.02) and nitrate (+ 2.12 ± 0.90 mmol/l, P = 0.04) were both significantly higher with mycoprotein relative to meat. The study population comprised metabolically healthy adults, therefore, changes in plasma lipids had little effect on cardiovascular risk scores (− 0.34% FRS for mycoprotein P = 0.24). Conclusions These results confirm potential cardiovascular benefits when displacing red and processed meat with mycoprotein in the diet. Longer trials in higher risk study populations are needed to fully elucidate suggested benefits for blood pressure and body composition. ClinicalTrials.gov Identifier: NCT03944421.
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.
Dietary patterns high in meat compromise both planetary and human health. Meat alternatives may help to facilitate meat reduction; however, the nutritional implications of displacing meat with meat alternatives does not appear to have been evaluated. Here, the ninth 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 replaced 25 %, 50 %, 75 % or 100 % of the current meat intake with a weighted mean of meat alternatives within the UK market. Model 2 compared different ingredient categories of meat alternative; vegetable, mycoprotein, a combination of bean and pea, tofu, nut and soya. Model 3 compared fortified v. unfortified meat alternatives. The models elicited significant shifts in nutrients. Overall, carbohydrate, fibre, sugars and Na increased, whereas reductions were found for protein, total and saturated fat, Fe and B12. Greatest effects were seen for vegetable-based (+24·63g/d carbohydrates), mycoprotein-based (-6·12g/d total fat), nut-based (-19·79g/d protein, +10·23g/d fibre; -4·80g/d saturated fat, +7·44g/d sugars), soya-based (+495·98mg/d Na) and tofu-based (+7·63mg/d Fe, -2·02μg/d B12). Our results suggest that meat alternatives can be a healthful replacement for meat if chosen correctly. Consumers should choose meat alternatives low in Na and sugar, high in fibre, protein and with high micronutrient density, to avoid compromising nutritional intake if reducing meat intake. Manufacturers and policy makers should consider fortification of meat alternatives with nutrients such as Fe and B12 and focus on reducing Na and sugar content.
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. 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. 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. 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. NCT02041975 (22/01/2014)
ABSTRACT Short chain fatty acids (SCFAs) derived from the human gut microbiota, and in particular propionate, may beneficially influence metabolic processes such as appetite regulation. Development of prebiotics that induce high propionate levels during fermentation is desirable. A total of 11 candidate prebiotics were screened to investigate their fermentation characteristics, with a focus on propionate production in mixed anaerobic batch culture of faecal bacteria. Further to this, a continuous 3-stage colonic fermentation model (simulating the human colon) was used to evaluate changes in microbial ecology, lactate and SCFA production of three 50:50 blends, comprising both slow and rapidly fermented prebiotics. In mixed batch culture: xylo-oligosaccharide, polydextrose and α-gluco-oligosaccharide were associated with the greatest increase in propionate. Polydextrose, α-gluco-oligosaccharide, β-1,4 glucan and oat fibre induced the greatest reductions in the acetate to propionate ratio. The most bifidogenic prebiotics were the oligosaccharides. Fermentation of a 50:50 blend of inulin and arabinoxylan, through the continuous 3-stage colonic fermentation model, induced a substantial and sustained release of propionate. The sustained release of propionate through the colon, if replicable in vivo, could potentially influence blood glucose, blood lipids and appetite regulation, however, dietary intervention studies are needed. Bifidogenic effects were also observed for the inulin and arabinoxylan blend and an increase synthesis of butyrate and lactate, thus indicating wider prebiotic potential.
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 Bacteroides fragilis, Escherichia coli, Streptococcus gallolyticus, Enterococcus faecalis and Fusobacterium nucleatum, 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.
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.
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.
Preload studies are used to investigate the satiating effects of foods and food ingredients. However, the design of preload studies is complex, with many methodological considerations influencing appetite responses. The aim of this pilot investigation was to determine acceptability, and optimise methods, for a future satiety preload study. Specifically, we investigated the effects of altering (i) energy intake at a standardised breakfast (gender-specific or non-gender specific), and (ii) the duration between mid-morning preload and ad libitum lunch meal, on morning appetite scores and energy intake at lunch.
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.
Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role for these phytochemicals in ameliorating aberrant glucose metabolism, high blood pressure and elevated blood lipids, and we discuss the potential mechanisms underpinning these observations. Searches for relevant literature published in English were conducted via PubMed and Science Direct. Based on published dietary intervention studies, there is convincing evidence to show that olive polyphenols, independently of olive lipids, reduce risk factors for metabolic syndrome, in particular by improving blood sugar and blood pressure control, and in reducing low density lipoprotein oxidation. There is more limited evidence to suggest that the consumption of olive polyphenols or related products can reduce body weight and visceral fat or impede weight gain, and similarly there are some limited data suggesting improved lipid profiles. There is some mechanistic data to support observations made in human volunteers, but further work is needed in this area. The consumption of olive polyphenols within the context of a healthy pattern of food intake may, in part, explain the reduced risk of metabolic disease associated with adherence to the Mediterranean diet.
Background: Middle Eastern countries are transitioning towards unhealthy western dietary patterns, leading to an increased risk of CVD. Evidence for healthy food based recommendations are therefore needed(1). Acai is an Amazonian fruit high in polyphenols, suggesting potential health benefits from its consumption(2). There is however poor evidence demonstrating improvements in health from consuming acai. Aim: This study aimed to investigate the beneficial effects of acai on vascular function. Design: Twenty-three healthy male volunteers, completed a randomized, placebo controlled, double-blind crossover acute intervention trial. Treatments were, the consumption of either an acai based smoothie, or a control smoothie, alongside a high fat meal. The primary endpoint was the assessment of endothelial function using flow-mediated dilatation (FMD).Results: We observed a significant improvement in vascular function at 2, 4 and 6 hrs following the acai meal relative to placebo. Conclusions: We demonstrate that consuming acai results in improvements in a well validated marker of (CVD) risk in overweight volunteers in an acute setting. These data suggest that acai may be a useful functional food as part of a healthy diet however future dietary intervention studies, with a chronic study design, in wider populations and with other biomarkers of disease risk are needed
BACKGROUND Açai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. OBJECTIVE The objective of the present study was to investigate the effect of açai 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 açai-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 -0.3% for the PS (P < 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after açai 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, açai 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 açai to health. This trial was registered at clinicaltrials.gov as NCT02292329.
Knowledge of the satiating properties of foods is key in the context of obesity.This pilot study aimed at providing data for optimization of future preload investigations with satiety as an endpoint.We investigated in forty healthy adults how altering the energy content of a sex‐specific versus non sex‐specific breakfast meal, and the time lapse between a mid‐morning orange juice preload and the next lunch test meal, could impact subsequent appetite responses and ad libitum energy intake. Female participants consumed either a 214 kcal (n=10) or a 266 kcal breakfast (n=10), equivalent to 10% of recommended daily energy intakes for females and males, respectively. Male participants (n=20) consumed a 266 kcal breakfast. All participants received a 250 ml orange juice preload 2 h after breakfast, 2 h (n=10) or 2.5 h (n=30) before the ad libitum lunch test meal. Appetite responses and study meal palatability were assessed during the visit using VAS questionnaires.A sex‐specific breakfast meal improved the correlation between male and female participants for appetite score measures, assessed using VAS, when compared to a non‐sex specific energy provision. Time of lunch test meal provision and time lapse between preload and lunch test meal did not significantly affect subjective appetite nor ad libitum energy intake.This validated method will be supportive for future testing of nutritional ingredient with satiating potential such as dietary fiber.Support or Funding InformationThis study was funded by Roquette (France). The funders were involved in the study design, however they had no role in running the experiments, data collection or analysis. Catherine Lefranc‐Millot and Laetitia Guerin‐Deremaux are employees at Roquette.
Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.—Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. FASEB J. 30, 2812‐2825 (2016). www.fasebj.org
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The fruit of the açai palm (Euterpe oleracea Mart.) is a rich source of potential bioactive phytochemicals, however neither its precise composition nor the putative benefits to health from its consumption have been fully characterised.This study aims to elucidate the composition of açai fruit pulp and to explore the potential of these extracts to confer protection in a cell culture based model of oxidative DNA damage.Extractions of açai pulps were dissolved in a 80% methanol (methanol: water, 80: 20 v/v) based solvent and the phytochemicals present in the extract were analysing by HPLC detector.Lipids were assessed via GC.The Folin-Ciocalteau assay was used to determine the purposes of providing a phytochemical rich food based comparator with established health benefits.Finally, protection against oxidative DNA damage was assessed in HT-29 cell lines exposed to hydrogen peroxide via the comet assay.Açai pulp extracts were found to be rich in flavonoids, anthocyanins and carotenoids.These extracts were found to protect against oxidative DNA damage (anti-genotoxicity).Açai extracts were more effective at preventing oxidative DNA damage than the blueberry extracts, although their antioxidant capacities as assessed by the FRAP assay were similar.These data shown that açai is a rich source of plant phytochemicals and that these chemicals may protect against oxidative stress in human colon cells (HT-29).Further work is needed to establish the digestive fate of these phytochemicals and to prove the beneficial effects in human.
The Hugh Sinclair Unit of Human Nutrition (HSUHN) at the University of Reading was founded in October 1995 with the appointment of Christine Williams OBE as the first Hugh Sinclair Chair in Human Nutrition. This was made possible by the competitively won funds from the estate and legacy of the late Professor Hugh Macdonald Sinclair (1910–1990). The vision for the newly established HSUHN was to ‘strengthen the evidence base for dietary recommendations for prevention of degenerative chronic diseases’. This has remained the research focus of the HSUHN under the leadership of Professors Christine Williams (1995–2005), Ian Rowland (2006–2013) and Julie Lovegrove (2014-present). Our mission is to improve population health and evaluate mechanisms of action for the effects of dietary components on health, which reflects Hugh Sinclair's life ambition within nutritional science. Over the past 20 years, the HSUHN has developed an international reputation within the nutrition science community, and in recognition of the 20th anniversary, this paper highlights Hugh Sinclair's contributions to the field of nutrition and key research achievements by members of the Unit.