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Small Intestinal Bacterial Overgrowth in Children: A State-Of-The-Art Review.
Avelar Rodriguez, D, Ryan, PM, Toro Monjaraz, EM, Ramirez Mayans, JA, Quigley, EM
Frontiers in pediatrics. 2019;7:363
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Small intestinal bacterial overgrowth (SIBO) occurs when microorganisms overpopulate the small intestine and is characterised by gastrointestinal symptoms such as abdominal pain, diarrhoea, and flatulence. This review focuses on paediatric SIBO, known to be increasing, with emphasis on the impact on gut microbiota. The gut microbiota is influenced by several factors including genetics, vaginal delivery, exercise and diet. SIBO in children has been studied in the context of stunting, irritable bowel syndrome (IBS), obesity, and related to use of proton pump inhibitors (PPIs). This review analysed 149 studies published since 2000 through till May 2019 with the aim of presenting the most up-to-date information. Risk factors included gastric acids and medications which suppress this activity, intestinal motility disturbances leading to bacterial overgrowth, anatomical anomalies where there is an absence of one or more intestinal valves, and poor socioeconomic status and diet. The review concluded that the recommended diagnosis is by methane and hydrogen breath testing and that Gold Standard treatment is antibiotic ‘rifaximin’ at 1,200 mg/d, reduced to 600 mg/d for 1 week in children. Alternative treatments discussed include FODMAP diets and probiotic protocols with best results coming from combining antibiotic and probiotic protocols. It concludes that SIBO in children is heterogenous and poorly understood and that a better diagnostic criteria is necessary in paediatrics.
Abstract
Small intestinal bacterial overgrowth (SIBO) is a heterogenous and poorly understood entity characterised by an excessive growth of select microorganisms within the small intestine. This excessive bacterial biomass, in turn, disrupts host physiology in a myriad of ways, leading to gastrointestinal and non-gastrointestinal symptoms and complications. SIBO is a common cause of non-specific gastrointestinal symptoms in children, such as chronic abdominal pain, abdominal distention, diarrhoea, and flatulence, amongst others. In addition, it has recently been implicated in the pathophysiology of stunting, a disease that affects millions of children worldwide. Risk factors such as acid-suppressive therapies, alterations in gastrointestinal motility and anatomy, as well as impoverished conditions, have been shown to predispose children to SIBO. SIBO can be diagnosed via culture-dependant or culture-independent approaches. SIBO's epidemiology is limited due to the lack of uniformity and consensus of its diagnostic criteria, as well as the paucity of literature available. Antibiotics remain the first-line treatment option for SIBO, although emerging modalities such as probiotics and diet manipulation could also have a role. Herein, we present a state-of-the-art-review which aims to comprehensively outline the most current information on SIBO in children, with particular emphasis on the gut microbiota.
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Raw Cow's Milk and Its Protective Effect on Allergies and Asthma.
Sozańska, B
Nutrients. 2019;11(2)
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In the last decades, a significant increase in the prevalence of allergic diseases and asthma has been observed. Living on a farm can reduce the risk of allergen sensitisation and allergic diseases in children. Most proposed explanations have been based on variations in the “hygiene hypothesis” and a possible effects on immune balance of a farm environment. Here, the author reviews epidemiological and experimental evidence for the documented protective effects of unpasteurised milk on allergies and asthma. Epidemiological studies from a number of countries show that children who consume raw milk early in life are less likely to develop allergies, independent of other factors. In one study that looked into possible components for this effect found that certain milk proteins (α-lactalbumin, β-lactoglobulin, and bovine serum albumin whey protein) reduced the risk of developing asthma . Total fat and protein content, amount of bacteria in the milk, and lactose levels were not associated with allergies or asthma. Another study found that higher levels of total fat and of omega-3 polyunsaturated fatty acids in raw milk had protective effects. The author discusses differences between raw and treated milk. Homogenisation changes the physical structure of fats and proteins, resulting in casein proteins being more easily adsorbed. The aim of heating milk, either through pasteurisation or UHT sterilisation, is to reduce bacterial numbers and growth, but it also affects heat-sensitive milk components, including whey proteins, immunoglobulins and lactoferrin, which have been shown to modulate the immune system. The author concludes that components of raw milk can influence immune function, and acknowledges the controversy with regards to raw milk carrying a risk of bacterial pathogens and that a proof based on controlled studies in infants is not possible due to ethical reasons.
Abstract
Living on a farm and having contact with rural exposures have been proposed as one of the most promising ways to be protected against allergy and asthma development. There is a significant body of epidemiological evidence that consumption of raw milk in childhood and adulthood in farm but also nonfarm populations can be one of the most effective protective factors. The observation is even more intriguing when considering the fact that milk is one of the most common food allergens in childhood. The exact mechanisms underlying this association are still not well understood, but the role of raw milk ingredients such as proteins, fat and fatty acids, and bacterial components has been recently studied and its influence on the immune function has been documented. In this review, we present the current understanding of the protective effect of raw milk on allergies and asthma.
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Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?
Newberry, F, Hsieh, SY, Wileman, T, Carding, SR
Clinical science (London, England : 1979). 2018;132(5):523-542
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Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease. Several studies have shown alterations in the gut microbiome (dysbiosis) in patients with ME/CFS. However, in focusing on the bacterial components of the microbiome, the viral component of the microbiome (known as the virome) has been neglected. Viruses can change the microbiome which can influence the health. This area is therefore important for research into ME/CFS. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the challenges associated with microbiome studies are discussed. A literature search was done and 11 papers were found that had examined the microbiome ME/CFS patients, dating from 1998 to 2017. It was not possible to compare the studies statistically but from looking at each one individually there is sufficient evidence to support the claim of an altered intestinal microbiome in ME/CFS patients. ME/CFS is multifactorial and potential dysbiosis should be considered to be only part of the picture. Future studies are needed to adopt standardized techniques and analyses. As research increases, it is becoming clear that the virome can directly and indirectly affect host health, and may play a role in the pathogenesis of ME/CFS.
Abstract
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
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Nutritional labelling for healthier food or non-alcoholic drink purchasing and consumption.
Crockett, RA, King, SE, Marteau, TM, Prevost, AT, Bignardi, G, Roberts, NW, Stubbs, B, Hollands, GJ, Jebb, SA
The Cochrane database of systematic reviews. 2018;2:CD009315
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Poor quality diets are a threat to health internationally and a challenge to health services. Implementing methods to change people's choices is difficult; even those who start making healthier choices often find it hard to maintain long-term. There is recognition that our environment has a powerful influence over our food choices and altering this may stimulate behavioural change. Nutritional labels provide information about the nutritional content of a food or drink. The type of information provided varies e.g. what nutrients they describe (e.g. macronutrients like fat or energy content) and the form also varies e.g. as a single number, as a proportion of a guideline for daily consumption, or with colours indicative of relative healthiness. Nutritional labelling has been rolled-out in many forms, across many countries but there is currently no consensus as to the best way of applying this information to products to stimulate healthier food choices. This review explored whether nutritional labels persuade consumers to buy alternative types of food and included 28 articles. Findings from these 28 articles suggest that nutritional labelling specially indicating energy content may cause people to opt to buy foods with a lower energy content in restaurants. This result (only based on 3 studies) suggests that nutritional labelling could be rolled-out on menus in restaurants, but high-quality research is required. Higher-quality research is also needed to explore the impact of nutritional labelling in shops and vending machines.
Abstract
BACKGROUND Nutritional labelling is advocated as a means to promote healthier food purchasing and consumption, including lower energy intake. Internationally, many different nutritional labelling schemes have been introduced. There is no consensus on whether such labelling is effective in promoting healthier behaviour. OBJECTIVES To assess the impact of nutritional labelling for food and non-alcoholic drinks on purchasing and consumption of healthier items. Our secondary objective was to explore possible effect moderators of nutritional labelling on purchasing and consumption. SEARCH METHODS We searched 13 electronic databases including CENTRAL, MEDLINE and Embase to 26 April 2017. We also handsearched references and citations and sought unpublished studies through websites and trials registries. SELECTION CRITERIA Eligible studies: were randomised or quasi-randomised controlled trials (RCTs/Q-RCTs), controlled before-and-after studies, or interrupted time series (ITS) studies; compared a labelled product (with information on nutrients or energy) with the same product without a nutritional label; assessed objectively measured purchasing or consumption of foods or non-alcoholic drinks in real-world or laboratory settings. DATA COLLECTION AND ANALYSIS Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of bias' tool and GRADE to assess the quality of evidence. We pooled studies that evaluated similar interventions and outcomes using a random-effects meta-analysis, and we synthesised data from other studies in a narrative summary. MAIN RESULTS We included 28 studies, comprising 17 RCTs, 5 Q-RCTs and 6 ITS studies. Most (21/28) took place in the USA, and 19 took place in university settings, 14 of which mainly involved university students or staff. Most (20/28) studies assessed the impact of labelling on menus or menu boards, or nutritional labelling placed on, or adjacent to, a range of foods or drinks from which participants could choose. Eight studies provided participants with only one labelled food or drink option (in which labelling was present on a container or packaging, adjacent to the food or on a display board) and measured the amount consumed. The most frequently assessed labelling type was energy (i.e. calorie) information (12/28).Eleven studies assessed the impact of nutritional labelling on purchasing food or drink options in real-world settings, including purchases from vending machines (one cluster-RCT), grocery stores (one ITS), or restaurants, cafeterias or coffee shops (three RCTs, one Q-RCT and five ITS). Findings on vending machines and grocery stores were not interpretable, and were rated as very low quality. A meta-analysis of the three RCTs, all of which assessed energy labelling on menus in restaurants, demonstrated a statistically significant reduction of 47 kcal in energy purchased (MD -46.72 kcal, 95% CI -78.35, -15.10, N = 1877). Assuming an average meal of 600 kcal, energy labelling on menus would reduce energy purchased per meal by 7.8% (95% CI 2.5% to 13.1%). The quality of the evidence for these three studies was rated as low, so our confidence in the effect estimate is limited and may change with further studies. Of the remaining six studies, only two (both ITS studies involving energy labels on menus or menus boards in a coffee shop or cafeteria) were at low risk of bias, and their results support the meta-analysis. The results of the other four studies which were conducted in a restaurant, cafeterias (2 studies) or a coffee shop, were not clearly reported and were at high risk of bias.Seventeen studies assessed the impact of nutritional labels on consumption in artificial settings or scenarios (henceforth referred to as laboratory studies or settings). Of these, eight (all RCTs) assessed the effect of labels on menus or placed on a range of food options. A meta-analysis of these studies did not conclusively demonstrate a reduction in energy consumed during a meal (MD -50 kcal, 95% CI -104.41, 3.88, N = 1705). We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies.Six laboratory studies (four RCTs and two Q-RCTs) assessed the impact of labelling a single food or drink option (such as chocolate, pasta or soft drinks) on energy consumed during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant difference in energy (kcal) consumed (SMD 0.05, 95% CI -0.17 to 0.27, N = 732). However, the confidence intervals were wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies.There was no evidence that nutritional labelling had the unintended harm of increasing energy purchased or consumed. Indirect evidence came from five laboratory studies that involved mislabelling single nutrient content (i.e. placing low energy or low fat labels on high-energy foods) during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant increase in energy (kcal) consumed (SMD 0.19, 95% CI -0.14to 0.51, N = 718). The effect was small and the confidence intervals wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence from these studies as very low, providing very little confidence in the effect estimate. AUTHORS' CONCLUSIONS Findings from a small body of low-quality evidence suggest that nutritional labelling comprising energy information on menus may reduce energy purchased in restaurants. The evidence assessing the impact on consumption of energy information on menus or on a range of food options in laboratory settings suggests a similar effect to that observed for purchasing, although the evidence is less definite and also of low quality.Accordingly, and in the absence of observed harms, we tentatively suggest that nutritional labelling on menus in restaurants could be used as part of a wider set of measures to tackle obesity. Additional high-quality research in real-world settings is needed to enable more certain conclusions.Further high-quality research is also needed to address the dearth of evidence from grocery stores and vending machines and to assess potential moderators of the intervention effect, including socioeconomic status.
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The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome.
Harper, A, Naghibi, MM, Garcha, D
Foods (Basel, Switzerland). 2018;7(2)
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Irritable bowel syndrome (IBS) affects 10-25% of the population worldwide but to date, no definitive effective treatment protocol has been established. This review explores the role of probiotics, bacteria and diet as potential causes of IBS and what role they may play in its treatment and management. The authors concluded that though there is clear evidence of alteration in the overall diversity and specific abundance of intestinal bacteria in IBS sufferers there, is no clear picture in relation to how this affects symptoms of IBS. Future randomised control trials are required to establish effectiveness of diet and probiotic supplementation as interventions in the management of IBS.
Abstract
Irritable bowel syndrome is a highly prevalent gastrointestinal disorder that threatens the quality of life of millions and poses a substantial financial burden on healthcare systems around the world. Intense research into the human microbiome has led to fascinating discoveries which directly and indirectly implicate the diversity and function of this occult organ in irritable bowel syndrome (IBS) pathophysiology. The benefit of manipulating the gastrointestinal microbiota with diet and probiotics to improve symptoms has been demonstrated in a wealth of both animal and human studies. The positive and negative mechanistic roles bacteria play in IBS will be explored and practical probiotic and dietary choices offered.
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The gut microbiome and irritable bowel syndrome.
Menees, S, Chey, W
F1000Research. 2018;7
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This study is a review of role of gut microbiome plays in the pathophysiology of Irritable bowel syndrome (IBS) sufferers. The author’s main objective was to identify the biomarkers that may lead into diagnosing and choosing best available therapy available from various interventions available for IBS that targets the gut microbiome, such as prebiotics, probiotics, non-absorbable antibiotics, diet and faecal microbial transplant (FMT). The authors concluded that to enable the right treatment for IBS sufferers it would be better to understand what constitutes a healthy gut rather than deciphering what is abnormal.
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders encountered in clinical practice. It is a heterogeneous disorder with a multifactorial pathogenesis. Recent studies have demonstrated that an imbalance in gut bacterial communities, or "dysbiosis", may be a contributor to the pathophysiology of IBS. There is evidence to suggest that gut dysbiosis may lead to activation of the gut immune system with downstream effects on a variety of other factors of potential relevance to the pathophysiology of IBS. This review will highlight the data addressing the emerging role of the gut microbiome in the pathogenesis of IBS and review the evidence for current and future microbiome based treatments.
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The microbiome and autoimmunity: a paradigm from the gut-liver axis.
Li, B, Selmi, C, Tang, R, Gershwin, ME, Ma, X
Cellular & molecular immunology. 2018;15(6):595-609
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The incidence of autoimmune and inflammatory diseases has been increasing worldwide. Changes in environmental factors, such as modern lifestyle, diet, antibiotics and hygiene are thought to play a critical role in the development of various autoimmune diseases. It is the mucosal microbial flora that is shaped by our environment and communicates with the innate and adaptive immune systems, and when disrupted, can lead to the loss of immune tolerance and dysregulated immune cells. This review paper provides an overview of the interactions between the intestinal microbiome and the immune system. It explains how these interactions affect host autoimmunity locally and systemically and sheds light on the molecular mechanisms, utilised by microbes that may contribute to systemic autoimmunity in genetically susceptible individuals. The links between the gut microbiome and various autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, as well as the gut-liver axis, involving intestinal microbiome and autoimmune liver diseases, are discussed in more detail.
Abstract
Microbial cells significantly outnumber human cells in the body, and the microbial flora at mucosal sites are shaped by environmental factors and, less intuitively, act on host immune responses, as demonstrated by experimental data in germ-free and gnotobiotic studies. Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown, as observed in rheumatic fever triggered by Streptococci via molecular mimicry, epitope spread and bystander effects. The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, multiple sclerosis and autoimmune liver disease. It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena. In fact, there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity, and microbial therapeutics is being investigated to prevent or halt autoimmune diseases. As a putative mechanism, it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens, giving rise to the differentiation of autoreactive Th17 cells and other T helper cells. This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity, with an emphasis on how dysbiosis may influence systemic autoimmunity. In particular, a gut-liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm, considering its anatomic and physiological connections.
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Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions.
Duggal, NA
Biogerontology. 2018;19(6):481-496
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Advancing age is accompanied by a compromised ability of older adults to combat bacterial and viral infections, increased risk of autoimmunity, poor vaccination responses and the re-emergence of latent infections. This review discusses current understanding of immunesenescence [the gradual deterioration of our immune system as we get older] and also focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals. Findings show that: - changes in nutrition and lifestyle can be an effective approach towards improving immune outcome in older adults but may be hard to achieve at a population level. - improving immune responses, such as the developments of vaccines, may be used as an early biomarker for anti-ageing effects. Authors conclude that immunomodulation represents a promising therapeutic approach to improve the health of older adults.
Abstract
It is widely accepted that ageing is accompanied by remodelling of the immune system, including reduced numbers of naïve T cells, increased senescent or exhausted T cells, compromise to monocyte, neutrophil and natural killer cell function and an increase in systemic inflammation. In combination these changes result in increased risk of infection, reduced immune memory, reduced immune tolerance and immune surveillance, with significant impacts upon health in old age. More recently it has become clear that the rate of decline in the immune system is malleable and can be influenced by environmental factors such as physical activity as well as pharmacological interventions. This review discusses briefly our current understanding of immunesenescence and then focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals.
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Association between plant-based diets and plasma lipids: a systematic review and meta-analysis.
Yokoyama, Y, Levin, SM, Barnard, ND
Nutrition reviews. 2017;75(9):683-698
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Plasma lipids play a prominent role in heart disease and modifiable factors such as diet and lifestyle can facilitate in preventing or developing hyperlipidemia. Previous research has suggested that vegetarian diets are associated with lower plasma lipid concentrations, however long-term impacts of consuming a plant-based diet (PBD) has not been studied. The aim of this research was to conduct a systematic review and meta-analysis for studies that have examined the relationship between PBDs and plasma lipids. Thirty observational studies and 19 clinical trials were included in this analysis and showed consumption of a PBD was significantly associated with lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not in triglyceride concentrations. Based on these results, the authors conclude PBDs could offer individuals and healthcare professionals an effective option for reducing heart disease. They also add that while dietary changes may not be as powerful as pharmaceutical drugs in reducing plasma lipids, dietary and pharmacologic interventions can work together.
Abstract
CONTEXT Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis. OBJECTIVE The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids. DATA SOURCES MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015. STUDY SELECTION The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids. DATA EXTRACTION Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model. RESULTS Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (-29.2 and -12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (-22.9 and -12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (-3.6 and -3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were -6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials. CONCLUSIONS Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides. SYSTEMATIC REVIEW REGISTRATION PROSPERO number CRD42015023783. Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023783.
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Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis.
Bailie, L, Loughrey, MB, Coleman, HG
Gastroenterology. 2017;152(1):92-104
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Colorectal cancer (CRC) is a heterogeneous disease thought to result from the accumulation of various aberrant mutations in the cells lining the colorectal mucosa. The aim of this systematic review and meta-analysis was to evaluate modifiable and lifestyle factors and the risk of serrated polyps (a type of growth that stick out from the surface of the colon or rectum) of the colorectum. A search of 3 databases yielded a potential 2446 studies for inclusion, from which 43 remained for systematic review. Results indicate that smoking, alcohol consumption, body fatness, dietary fat and meat consumption increased the risk of developing serrated polyps. Whereas, nonsteroidal anti-inflammatory drugs, aspirin and dietary folate decreased this risk. Authors conclude that their findings strengthen public health messages promoting awareness and change in order to reduce the risk of these precancerous lesions and consequently CRC.
Abstract
BACKGROUND & AIMS Certain subsets of colorectal serrated polyps (SP) have malignant potential. We performed a systematic review and meta-analysis to investigate the association between modifiable lifestyle factors and risk for SPs. METHODS We conducted a systematic search of Medline, Embase, and Web of Science for observational or interventional studies that contained the terms risk or risk factor, and serrated or hyperplastic, and polyps or adenomas, and colorectal (or synonymous terms), published by March 2016. Titles and abstracts of identified articles were independently reviewed by at least 2 reviewers. Adjusted relative risk (RR) and 95% confidence interval (CI) were combined using random effects meta-analyses to assess the risk of SP, when possible. RESULTS We identified 43 studies of SP risk associated with 7 different lifestyle factors: smoking, alcohol, body fatness, diet, physical activity, medication, and hormone-replacement therapy. When we compared the highest and lowest categories of exposure, factors we found to significantly increase risk for SP included tobacco smoking (RR, 2.47; 95% CI, 2.12-2.87), alcohol intake (RR, 1.33; 95% CI, 1.17-1.52), body mass index (RR, 1.40; 95% CI, 1.22-1.61), and high intake of fat or meat. Direct associations for smoking and alcohol, but not body fat, tended to be stronger for sessile serrated adenomas/polyps than hyperplastic polyps. In contrast, factors we found to significantly decrease risks for SP included use of nonsteroidal anti-inflammatory drugs (RR, 0.77; 95% CI, 0.65-0.92) or aspirin (RR, 0.81; 95% CI, 0.67-0.99), as well as high intake of folate, calcium, or fiber. No significant associations were detected between SP risk and physical activity or hormone replacement therapy. CONCLUSIONS Several lifestyle factors, most notably smoking and alcohol, are associated with SP risk. These findings enhance our understanding of mechanisms of SP development and indicate that risk of serrated pathway colorectal neoplasms could be reduced with lifestyle changes.