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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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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 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.
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Impact of Mediterranean diet on metabolic syndrome, cancer and longevity.
Di Daniele, N, Noce, A, Vidiri, MF, Moriconi, E, Marrone, G, Annicchiarico-Petruzzelli, M, D'Urso, G, Tesauro, M, Rovella, V, De Lorenzo, A
Oncotarget. 2017;8(5):8947-8979
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There is a growing link between being overweight or obese and the onset of certain cancers. The latest research shows that 30-35% of cancers may have a link to diet, and that metabolic syndromes involving obesity encourage the body to store metabolically active ‘sick fats’ in adipose tissue, which in turn causes inflammation and creates an environment for cancer to thrive. The Mediterranean diet (MD) is considered one of the healthiest in the world and rates of cancer and metabolic syndrome are lower in the Mediterranean region versus Northern Europe suggesting it may be helpful in prevention of obesity and cancer. The MD is characterised as a balanced combination of fruit and vegetables, fish, cereals, and polyunsaturated fats (such as olive oil), with a reduced consumption of meat and dairy products and moderate intake of alcohol, primarily red wine. The nutrients that are found in abundance in the MD have a mixture of anti-cancer, anti-inflammatory, and anti-obesity properties thanks to antioxidant elements, fibre and healthy polyunsaturated fats. Studies show these nutrients can help support multiple metabolic markers such as blood pressure, cholesterol, inflammation, and insulin sensitivity. In 2010, UNESCO proclaimed the MD as “World Cultural Heritage”. This diet represents a behavioural model, a “way of life”, that can ensure longer life expectancy and improve quality of life itself.
Abstract
Obesity symbolizes a major public health problem. Overweight and obesity are associated to the occurrence of the metabolic syndrome and to adipose tissue dysfunction. The adipose tissue is metabolically active and an endocrine organ, whose dysregulation causes a low-grade inflammatory state and ectopic fat depositions. The Mediterranean Diet represents a possible therapy for metabolic syndrome, preventing adiposopathy or "sick fat" formation.The Mediterranean Diet exerts protective effects in elderly subjects with and without baseline of chronic diseases. Recent studies have demonstrated a relationship between cancer and obesity. In the US, diet represents amount 30-35% of death causes related to cancer. Currently, the cancer is the second cause of death after cardiovascular diseases worldwide. Furthermore, populations living in the Mediterranean area have a decreased incidence of cancer compared with populations living in Northern Europe or the US, likely due to healthier dietary habits. The bioactive food components have a potential preventive action on cancer. The aims of this review are to evaluate the impact of Mediterranean Diet on onset, progression and regression of metabolic syndrome, cancer and on longevity.
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The microbiome: A key regulator of stress and neuroinflammation.
Rea, K, Dinan, TG, Cryan, JF
Neurobiology of stress. 2016;4:23-33
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This study discusses the concept of intestinal microbiota as the key regulator involved in energy regulation, gut barrier function, protection from pathogens, and immune system function amongst others. The gut microbiota is the complex community of microorganisms that lives in the digestive tracts of humans. The main aim of this study is to summarise the role of gastrointestinal microbiota in fundamental physiological and pathophysiological processes and thereafter to understand and treat a range of stress and immune-related disorders. This review outlines the numerous complex relationships between gastrointestinal microbiota, stress and immune responses at the three critical stages of life The authors concluded that the evidence from this study suggests that resilience to stress and immune-related disorders and dysfunction of stress and immune systems may be dependent on the diversity and complexity of gastrointestinal microbiota. However, gut microbiota mediated relationship to stress and neuro-inflammation is still unconfirmed as previous studies mostly, have largely been, preclinical and further studies are warranted.
Abstract
There is a growing emphasis on the relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and health/disease, including brain health and disorders of the central nervous system. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the brain, glands, gut, immune cells and gastrointestinal microbiota that communicate in a complex multidirectional manner to maintain homeostasis. Changes in this environment can lead to a broad spectrum of physiological and behavioural effects including hypothalamic-pituitary-adrenal (HPA) axis activation, and altered activity of neurotransmitter systems and immune function. While an appropriate, co-ordinated physiological response, such as an immune or stress response are necessary for survival, a dysfunctional response can be detrimental to the host contributing to the development of a number of CNS disorders. In this review, the involvement of the gastrointestinal microbiota in stress-mediated and immune-mediated modulation of neuroendocrine, immune and neurotransmitter systems and the consequential behaviour is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in stress-related disorders as a consequence of neuroinflammatory processes.
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Risk factors for pancreatic cancer: a summary review of meta-analytical studies.
Maisonneuve, P, Lowenfels, AB
International journal of epidemiology. 2015;44(1):186-98
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Pancreatic cancer (PC) is one of the four or five most common causes of cancer mortality in developed countries. The aim of this review was to summarize results from pooled analyses and meta-analyses to estimate the fraction of PCs attributable to many different risk factors. A comprehensive review of the literature was carried out by searching for meta-analytical studies on the association between specific risk factors and PC risk or multiple cancer sites. Results indicate that PC has a multifactorial aetiology. All identified factors can be combined into a specific aetiological (the philosophy or study of causation) pathway for PC. The main pathways include insulin resistance (central adiposity, diabetes, metabolic syndrome), inflammation (tobacco, alcohol, pancreatitis), DNA damage (tobacco, red meat) and haemostasis (blood group, history of thrombosis). Authors conclude that about two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.
Abstract
BACKGROUND The aetiology of pancreatic cancer (PC) has been extensively studied and is the subject of numerous meta-analyses and pooled analyses. We have summarized results from these pooled and meta-analytical studies to estimate the fraction of PCs attributable to each of the identified risk factors. METHODS Using a comprehensive strategy, we retrieved 117 meta-analytical or pooled reports dealing with the association between specific risk factors and PC risk. We combined estimates of relative risk and estimates of exposure to calculate the fraction of PCs caused or prevented by a particular exposure. RESULTS Tobacco smoking ('strong' evidence) and Helicobacter pylori infection ('moderate' evidence) are the major risk factors associated with PC, with respective estimated population attributable fractions of 11-32% and 4-25%. The major protective factors are history of allergy ('strong' evidence) and increasing fruit or folate intake ('moderate' evidence), with respective population preventable fractions of 3-7% and 0-12%. CONCLUSIONS We summarized results of 117 meta-analytical or pooled data reports dealing with 37 aetiological exposures, to obtain robust information about the suspected causes of PC. By combining these estimates with their prevalences in the population, we calculated population attributable or population preventable fractions. About two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.