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Human Gut Microbiota and Gastrointestinal Cancer.
Meng, C, Bai, C, Brown, TD, Hood, LE, Tian, Q
Genomics, proteomics & bioinformatics. 2018;16(1):33-49
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In this article the authors review research on the influence of the human gut microbiota on the development and progression of gastrointestinal cancers, and go into significant detail about the molecular mechanisms involved. Helicobacter pylori is a known risk factor for gastric cancer (GC) but other dysbiotic changes in the gut microbiota are also observed in GC. On the other hand, H. pylori is associated with a decreased risk for oesophageal cancer (OC). An increase in gram-negative bacteria is associated with OC, whilst gram-positive bacteria are dominant in a healthy oesophagus. Dietary factors are associated with the risk for colorectal cancer (CRC) and may be due to their effect on the bacterial composition of the bowel. The authors explore possible mechanisms for these links. Although the liver is considered sterile, carcinogenesis can be influenced by the gut microbiota through pathogens and bacterial metabolites which can disturb metabolic pathways and immune responses in the liver. In pancreatic cancer (PC), the gut microbiota may influence carcinogenesis by promoting inflammation. In addition to various lifestyle factors, H. pylori is a risk factor for PC. The authors also review the use of prebiotics, probiotics, synbiotics (a combination of pre- and pro-biotics) and Traditional Chinese Medicine as an adjunct to conventional cancer treatment to reduce side effects, as well as their potential preventive mechanisms.
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Fructose metabolism and metabolic disease.
Hannou, SA, Haslam, DE, McKeown, NM, Herman, MA
The Journal of clinical investigation. 2018;128(2):545-555
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Sugar consumption is thought to be a contributing factor in the increase in diabetes and obesity and the associated risk of cardiovascular disease worldwide. Sucrose (table sugar) and high fructose corn syrup contain almost equal amounts of fructose and glucose and are commonly added to processed foods. Whilst long-term studies are lacking, some short-term intervention studies show that fructose can impair lipid metabolism and insulin sensitivity in humans. This article reviews the biochemistry and molecular genetics of fructose metabolism as well as potential mechanisms by which excessive fructose consumption contributes to cardiometabolic disease. Fructose absorption in the human intestine is saturable, and there is a large range in capacity to absorb fructose between individuals, and unabsorbed fructose may contribute to gastrointestinal symptoms including pain and bloating. Fructose concentrations in the blood can increase 10-fold after consumption, but are rapidly cleared, mostly by the liver, where it provides substrate for metabolic processes, but may also be involved in signalling functions. Fructose may enhance glucose uptake by the liver and storage as glycogen and lipids. It may also increase production of uric acid which is implicated with gout. Excessive fructose consumption affects lipid metabolism and may contribute to fat accumulation in the liver and increase circulating triglycerides, a risk factor for heart disease. In animal models it also induces increased insulin levels. Fructose is one of the sweetest sugars which may affect appetite and overeating. It may also induce addiction-like behaviours such as binging and dependence in part by stimulating dopaminergic pathways. It also appears to induce leptin resistance which further increases food intake and obesity.
Abstract
Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.
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Circadian Rhythms, Metabolism, and Chrononutrition in Rodents and Humans.
Johnston, JD, Ordovás, JM, Scheer, FA, Turek, FW
Advances in nutrition (Bethesda, Md.). 2016;7(2):399-406
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Chrononutrition is an emerging field that links the body’s metabolism to its endogenous circadian rhythm. It is now recognised that numerous circadian clocks are found within all major tissues and most cells of the body. This complex network of clocks influences a wide range of biological processes including neuronal, endocrine, metabolic and behavioural function. When there is a disruption in a single circadian clock, whole-organism homeostasis can be impacted, potentially resulting in the development of disease. This review explains the potential mechanisms by which circadian clocks influence biological processes through transgenic animal studies, and how they are being translated to human genetics and metabolomics. The principles of chrononutrition are clinically significant factors that should be considered when managing and treating metabolic disease, as well as maintaining health in the general population.
Abstract
Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial responses. Recent work has elucidated the metabolic roles of circadian clocks in key metabolic tissues, including liver, pancreas, white adipose, and skeletal muscle. For example, tissue-specific clock disruption in a single peripheral organ can cause obesity or disruption of whole-organism glucose homeostasis. This review explains mechanistic insights gained from transgenic animal studies and how these data are being translated into the study of human genetics and physiology. The principles of chrononutrition have already been demonstrated to improve human weight loss and are likely to benefit the health of individuals with metabolic disease, as well as of the general population.
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Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.
Johnston, CA, Moreno, JP, Foreyt, JP
Current atherosclerosis reports. 2014;16(12):457
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Obesity is a metabolic risk factor for Type 2 diabetes (T2D) and cardiovascular diseases(CVD). This study was carried out to measure the effectiveness of lifestyle interventions on cardiovascular morbidity and mortality. 5145 overweight and obese patients with T2D were randomised assigned in groups with lifestyle interventions of weight loss through exercise and reduced calorie intake. The control group were given diabetes support and education. The data from this study suggest that lifestyle interventions were effective in weight loss and management of the CVD. However reducing the risk of CVD in comparison to the control group was not determined.
Abstract
Look AHEAD (Action for Health in Diabetes) was a randomized controlled trial that examined the impact of long-term participation in an intensive weight loss intervention on cardiovascular disease (CVD) morbidity and mortality in people with type 2 diabetes (T2D). The results from this trial suggest that intensive lifestyle interventions are effective in helping patients to achieve management of cardiovascular risk factors and reducing the need to initiate medication usage to manage these conditions, though the benefits in terms of the prevention of CVD morbidity and mortality beyond those achieved through aggressive medical management of hypertension and dyslipidemia is not clear. Additional benefits of participation in an intensive lifestyle intervention such as lowered chronic kidney disease risk, blood pressure, medication usage, improved sleep apnea, and partial remission of diabetes are discussed.
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Vegetarian dietary patterns and mortality in Adventist Health Study 2.
Orlich, MJ, Singh, PN, Sabaté, J, Jaceldo-Siegl, K, Fan, J, Knutsen, S, Beeson, WL, Fraser, GE
JAMA internal medicine. 2013;173(13):1230-8
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Vegetarian diets have been associated with reduced risk of several chronic cardiometabolic diseases. The aim of this cohort study was to evaluate the effect of vegetarian diets on mortality. The study followed 73,308 male and female Seventh-day Adventists for a mean of 5.79 years. At baseline, just under half were non-vegetarians. Vegetarians had a lower mortality than non-vegetarians: death rates (deaths per 1000 person-years) were 5.4 for vegans, 5.61 for ovo-lacto vegetarians and 5.33 for pesco-vegetarians, which were significantly lower than that of non-vegetarians (6.61). After adjustment for a variety of factors, the lowered hazard ratio seen with vegetarian diets only remained statistically significant in pesco-vegetarians (compared to non-vegetarians). The non-vegetarians had on average higher rates of other risk factors, such as smoking, they consumed more alcohol, exercised less and had lower educational level. The authors concluded that vegetarian dietary patterns were associated with lower mortality.
Abstract
IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality. DESIGN Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. SETTING Adventist Health Study 2 (AHS-2), a large North American cohort. PARTICIPANTS A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. EXPOSURES Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASURE The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. RESULTS There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.