Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo

The decreased cancer risk associated with consumption of olive oil may be due to the presence of phenolics which can modulate pathways including apoptosis and invasion that are relevant to carcinogenesis. We have previously shown that a virgin olive oil phenolics extract (OVP) inhibited invasion of HT115 colon cancer cells in vitro. In the current study we assessed the in vitro effects of OVP (25 μg mL(-1)) on HT115 cell migration, spreading and integrin expression. Furthermore, the anti-metastatic activity of OVP - at a dose equivalent to 25 mg per kg per day for 2, 8 or 10 weeks - was assessed in a Severe Combined ImmunoDeficiency (SCID) Balb-c mouse model. After 24 h OVP did not inhibit cell migration but significantly reduced cell spreading on fibronectin (65% of control; p < 0.05) and expression of a range of α and β integrins was modulated. In vivo, OVP by gavage significantly (p < 0.05) decreased not only tumour volume but also the number of metastases in SCID Balb-c mice. Collectively, the data suggest that - possibly through modulation of integrin expression - OVP decreases invasion in vitro and also inhibits metastasis in vivo.

Impacts of plant-based foods in ancestral hominin diets on the metabolism and function of gut microbiota in vitro

Ancestral human populations had diets containing more indigestible plant material than present-day diets in industrialized countries. One hypothesis for the rise in prevalence of obesity is that physiological mechanisms for controlling appetite evolved to match a diet with plant fiber content higher than that of present-day diets. We investigated how diet affects gut microbiota and colon cells by comparing human microbial communities with those from a primate that has an extreme plant-based diet, namely, the gelada baboon, which is a grazer. The effects of potato (high starch) versus grass (high lignin and cellulose) diets on human-derived versus gelada-derived fecal communities were compared in vitro. We especially focused on the production of short-chain fatty acids, which are hypothesized to be key metabolites influencing appetite regulation pathways. The results confirmed that diet has a major effect on bacterial numbers, short-chain fatty acid production, and the release of hormones involved in appetite suppression. The potato diet yielded greater production of short-chain fatty acids and hormone release than the grass diet, even in the gelada cultures, which we had expected should be better adapted to the grass diet. The strong effects of diet on hormone release could not be explained, however, solely by short-chain fatty acid concentrations. Nuclear magnetic resonance spectroscopy found changes in additional metabolites, including betaine and isoleucine, that might play key roles in inhibiting and stimulating appetite suppression pathways. Our study results indicate that a broader array of metabolites might be involved in triggering gut hormone release in humans than previously thought. IMPORTANCE: One theory for rising levels of obesity in western populations is that the body's mechanisms for controlling appetite evolved to match ancestral diets with more low-energy plant foods. We investigated this idea by comparing the effects of diet on appetite suppression pathways via the use of gut bacterial communities from humans and gelada baboons, which are modern-day primates with an extreme diet of low-energy plant food, namely, grass. We found that diet does play a major role in affecting gut bacteria and the production of a hormone that suppresses appetite but not in the direction predicted by the ancestral diet hypothesis. Also, bacterial products were correlated with hormone release that were different from those normally thought to play this role. By comparing microbiota and diets outside the natural range for modern humans, we found a relationship between diet and appetite pathways that was more complex than previously hypothesized on the basis of more-controlled studies of the effects of single compounds.

Effect of breadmaking process on In Vitro gut microbiota parameters in irritable bowel syndrome

A variety of foods have been implicated in symptoms of patients with Irritable Bowel Syndrome (IBS) but wheat products are most frequently cited by patients as a trigger. Our aim was to investigate the effects of breads, which were fermented for different lengths of time, on the colonic microbiota using in vitro batch culture experiments. A set of in vitro anaerobic culture systems were run over a period of 24 h using faeces from 3 different IBS donors (Rome Criteria–mainly constipated) and 3 healthy donors. Changes in gut microbiota during a time course were identified by fluorescence in situ hybridisation (FISH), whilst the small -molecular weight metabolomic profile was determined by NMR analysis. Gas production was separately investigated in non pH-controlled, 36 h batch culture experiments. Numbers of bifidobacteria were higher in healthy subjects compared to IBS donors. In addition, the healthy donors showed a significant increase in bifidobacteria (P<0.005) after 8 h of fermentation of a bread produced using a sourdough process (type C) compared to breads produced with commercial yeasted dough (type B) and no time fermentation (Chorleywood Breadmaking process) (type A). A significant decrease of δ-Proteobacteria and most Gemmatimonadetes species was observed after 24 h fermentation of type C bread in both IBS and healthy donors. In general, IBS donors showed higher rates of gas production compared to healthy donors. Rates of gas production for type A and conventional long fermentation (type B) breads were almost identical in IBS and healthy donors. Sourdough bread produced significantly lower cumulative gas after 15 h fermentation as compared to type A and B breads in IBS donors but not in the healthy controls. In conclusion, breads fermented by the traditional long fermentation and sourdough are less likely to lead to IBS symptoms compared to bread made using the Chorleywood Breadmaking Process.

Increased whole grain consumption does not affect blood biochemistry, body composition or gut microbiology in healthy low habitual whole grain consumers

Background Whole grain (WG) foods have been suggested to reduce the risk of cardiovascular disease, but studies are inconsistent and effects on cardiovascular risk markers are not clear. Objective The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on overall dietary intake, body composition, blood pressure (BP), blood lipids, blood glucose, gastrointestinal microbiology and gastrointestinal symptoms in healthy, middle-age adults with habitual WG intake < 24 g/d. The trial was registered as ISRCTN36521837. Methods Eligible subjects (12 men, 21 women, aged 40-65 y and BMI 20-35 kg/m2) were identified using food frequency questionnaires and subsequently completed 3-day food diaries (3DFD) to confirm habitual WG consumption. Subjects consumed diets high in WG (> 80 g/d) or low in WG (< 16 g/d, refined grain [RG] diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence was achieved by specific dietary advice and provision of a range of cereal food products. The 3DFD, diet compliance diaries and plasma alkylresorcinols (ARs) were used to verify compliance. Results On the WG intervention, consumption increased from 28 g/d to 168 g/d (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and total fiber intake (P < 0.001), without any effect on energy or other macronutrients. While there were no effects on studied parameters, there were trends towards increased 24 h fecal weight (P = 0.08) and reduction in body weight (P = 0.10) and BMI (P = 0.08) during the WG compared to the RG period. Conclusion A combination of dietary advice and provision of commercially available food items enabled subjects with a low-moderate habitual consumption of WG to substantially increase their WG intake, but there was little effect on blood biochemical parameters, body composition, BP, fecal measurements or gut microbiology.

Gut permeability in autism spectrum disorders

Objective To test whether gut permeability is increased in autism spectrum disorders (ASD) by evaluating gut permeability in a population-derived cohort of children with ASD compared with age- and intelligence quotient-matched controls without ASD but with special educational needs (SEN). Patients and Methods One hundred thirty-three children aged 10–14 years, 103 with ASD and 30 with SEN, were given an oral test dose of mannitol and lactulose and urine collected for 6 hr. Gut permeability was assessed by measuring the urine lactulose/mannitol (L/M) recovery ratio by electrospray mass spectrometry-mass spectrometry. The ASD group was subcategorized for comparison into those without (n = 83) and with (n = 20) regression. Results There was no significant difference in L/M recovery ratio (mean (95% confidence interval)) between the groups with ASD: 0.015 (0.013–0.018), and SEN: 0.014 (0.009–0.019), nor in lactulose, mannitol, or creatinine recovery. No significant differences were observed in any parameter for the regressed versus non-regressed ASD groups. Results were consistent with previously published normal ranges. Eleven children (9/103 = 8.7% ASD and 2/30 = 6.7% SEN) had L/M recovery ratio > 0.03 (the accepted normal range cut-off), of whom two (one ASD and one SEN) had more definitely pathological L/M recovery ratios > 0.04. Conclusion There is no statistically significant group difference in small intestine permeability in a population cohort-derived group of children with ASD compared with a control group with SEN. Of the two children (one ASD and one SEN) with an L/M recovery ratio of > 0.04, one had undiagnosed asymptomatic celiac disease (ASD) and the other (SEN) past extensive surgery for gastroschisis.

Impact of dietary polydextrose fiber on the human gut metabolome

The aim of the present study was to elucidate the impact of polydextrose PDX an soluble fiber, on the human fecal metabolome by high-resolution nuclear magnetic resonance (NMR) spectroscopy-based metabolomics in a dietary intervention study (n = 12). Principal component analysis (PCA) revealed a strong effect of PDX consumption on the fecal metabolome, which could be mainly ascribed to the presence of undigested fiber and oligosaccharides formed from partial degradation of PDX. Our results demonstrate that NMR-based metabolomics is a useful technique for metabolite profiling of feces and for testing compliance to dietary fiber intake in such trials. In addition, novel associations between PDX and the levels of the fecal metabolites acetate and propionate could be identified. The establishment of a correlation between the fecal metabolome and levels of Bifidobacterium (R2 = 0.66) and Bacteroides (R2 = 0.46) demonstrates the potential of NMR-based metabolomics to elucidate metabolic activity of bacteria in the gut.

Prebiotics modulate the effects of antibiotics on gut microbial diversity and functioning in vitro

Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation—another method used to modulate gut composition and function—could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota.

Human gut microbiota and its relationship to health and disease

Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics.

Apples and cardiovascular health: is the gut microbiota a core consideration?

There is now considerable scientific evidence that a diet rich in fruits and vegetables can improve human health and protect against chronic diseases. However, it is not clear whether different fruits and vegetables have distinct beneficial effects. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fiber. A major proportion of the bioactive components in apples, including the high molecular weight polyphenols, escape absorption in the upper gastrointestinal tract and reach the large intestine relatively intact. There, they can be converted by the colonic microbiota to bioavailable and biologically active compounds with systemic effects, in addition to modulating microbial composition. Epidemiological studies have identified associations between frequent apple consumption and reduced risk of chronic diseases such as cardiovascular disease. Human and animal intervention studies demonstrate beneficial effects on lipid metabolism, vascular function and inflammation but only a few studies have attempted to link these mechanistically with the gut microbiota. This review will focus on the reciprocal interaction between apple components and the gut microbiota, the potential link to cardiovascular health and the possible mechanisms of action.

Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons

It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65-80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.

The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons

Despite the accumulating knowledge on the development and establishment of the gut microbiota, its role as a reservoir for multidrug resistance is not well understood. This study investigated the prevalence and persistence patterns of an integrase gene (int1), used as a proxy for integrons (which often carry multiple antimicrobial resistance genes), in the fecal microbiota of 147 mothers and their children sampled longitudinally from birth to 2 years. The study showed the int1 gene was detected in 15% of the study population, and apparently more persistent than the microbial community structure itself. We found int1 to be persistent throughout the first two years of life, as well as between mothers and their 2-year-old children. Metagenome sequencing revealed integrons in the gut meta-mobilome that were associated with plasmids and multidrug resistance. In conclusion, the persistent nature of integrons in the infant gut microbiota makes it a potential reservoir of mobile multidrug resistance.

Prebiotic potential of a maize-based soluble fibre and impact of dose on the human gut microbiota

Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12g and 18g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention.