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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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How and why weight stigma drives the obesity 'epidemic' and harms health.
Tomiyama, AJ, Carr, D, Granberg, EM, Major, B, Robinson, E, Sutin, AR, Brewis, A
BMC medicine. 2018;16(1):123
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Weight stigma is defined as the social rejection and devaluation that accrues to those who do not comply with prevailing social norms of adequate body weight and shape. In this opinion-based study, authors discuss that: • Latest literature indicates that weight stigma can trigger physiological and behavioural changes linked to poor metabolic health and increased weight gain. • Healthcare is a setting in which weight stigma is particularly pervasive, with significant consequences for the health of higher-weight patients. This stigma has direct and observable consequences for the quality and nature of services provided to those with obesity. • Stigma may be an unintended consequence of anti-obesity efforts, undermining their intended effect. Moreover, focusing solely on obesity treatment runs the risk of missing other diagnoses. • The science of weight stigma crystallizes a key point for future success – to tackle the obesity ‘epidemic’ we must tackle the parallel epidemic of weight stigma. • Public service messages are needed to educate people about the stigma, discrimination, and challenges facing higher-weight individuals. Authors conclude that to advance as an equal society, healthcare providers should lead the way for weight stigma eradication.
Abstract
BACKGROUND In an era when obesity prevalence is high throughout much of the world, there is a correspondingly pervasive and strong culture of weight stigma. For example, representative studies show that some forms of weight discrimination are more prevalent even than discrimination based on race or ethnicity. DISCUSSION In this Opinion article, we review compelling evidence that weight stigma is harmful to health, over and above objective body mass index. Weight stigma is prospectively related to heightened mortality and other chronic diseases and conditions. Most ironically, it actually begets heightened risk of obesity through multiple obesogenic pathways. Weight stigma is particularly prevalent and detrimental in healthcare settings, with documented high levels of 'anti-fat' bias in healthcare providers, patients with obesity receiving poorer care and having worse outcomes, and medical students with obesity reporting high levels of alcohol and substance use to cope with internalized weight stigma. In terms of solutions, the most effective and ethical approaches should be aimed at changing the behaviors and attitudes of those who stigmatize, rather than towards the targets of weight stigma. Medical training must address weight bias, training healthcare professionals about how it is perpetuated and on its potentially harmful effects on their patients. CONCLUSION Weight stigma is likely to drive weight gain and poor health and thus should be eradicated. This effort can begin by training compassionate and knowledgeable healthcare providers who will deliver better care and ultimately lessen the negative effects of weight stigma.
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Predictors of weight stigma experienced by middle-older aged, general-practice patients with obesity in disadvantaged areas of Australia: a cross-sectional study.
Spooner, C, Jayasinghe, UW, Faruqi, N, Stocks, N, Harris, MF
BMC public health. 2018;18(1):640
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People in higher categories of obesity are at substantially increased health risk because mortality increases sharply as body mass index rises above 30. In addition to physical health risks, people with obesity commonly experience weight-related stigma. The aim of this study was to identify predictors of perceived weight stigma among patients with obesity attending general practices in socioeconomically disadvantaged urban areas of Australia. This is a cross-sectional study for which data from telephone interviews with patients with obesity were used. Patients were recruited from 17 general practices in socioeconomically disadvantaged areas of Sydney and Adelaide. Results indicate that one-third of the sample had experienced direct forms of weight discrimination in the week before being interviewed. Furthermore, weight discrimination was more likely to be experienced by patients in higher obesity categories, who were not employed, who spoke a language other than English at home and who had lower scores on the Health Literacy Questionnaire domain (that measures the ability to actively engage with healthcare providers). Authors conclude that weight stigma may compound other forms of social disadvantage. Thus, strategies are needed to address weight stigma at the individual, system and population levels and to educate primary care providers to be more alert to the needs of their patients with obesity.
Abstract
BACKGROUND Rates of obesity have increased globally and weight stigma is commonly experienced by people with obesity. Feeling stigmatised because of one's weight can be a barrier to healthy eating, physical activity and to seeking help for weight management. The aim of this study was to identify predictors of perceived weight among middle-older aged patients with obesity attending general practices in socioeconomically disadvantaged urban areas of Australia. METHODS As part of a randomised clinical trial in Australia, telephone interviews were conducted with 120 patients from 17 general practices in socioeconomically disadvantaged of Sydney and Adelaide. Patients were aged 40-70 years with a BMI ≥ 30 kg/m2. The interviews included questions relating to socio-demographic variables (e.g. gender, language spoken at home), experiences of weight-related discrimination, and the Health Literacy Questionnaire (HLQ). Multi-level logistic regression data analysis was undertaken to examine predictors of recent experiences of weight-related discrimination ("weight stigma"). RESULTS The multi-level model showed that weight stigma was positively associated with obesity category 2 (BMI = 35 to < 40; OR 4.47 (95% CI 1.03 to 19.40)) and obesity category 3 (BMI = ≥ 40; OR 27.06 (95% CI 4.85 to 150.95)), not being employed (OR 7.70 (95% CI 2.17 to 27.25)), non-English speaking backgrounds (OR 5.74 (95% CI 1.35 to 24.45)) and negatively associated with the HLQ domain: ability to actively engage with healthcare providers (OR 0.12 (95% CI 0.05 to 0.28)). There was no association between weight stigma and gender, age, education or the other HLQ domains examined. CONCLUSIONS Weight stigma disproportionately affected the patients with obesity most in need of support to manage their weight: those with more severe obesity, from non-English speaking backgrounds and who were not in employment. Additionally, those who had experienced weight stigma were less able to actively engage with healthcare providers further compounding their disadvantage. This suggests the need for a more proactive approach to identify weight stigma by healthcare providers. Addressing weight stigma at the individual, system and population levels is recommended. TRIAL REGISTRATION The trial was registered with the Australian Clinical Trials Registry ACTRN126400102162 .
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Swimming pool exposure is associated with autonomic changes and increased airway reactivity to a beta-2 agonist in school aged children: A cross-sectional survey.
Cavaleiro Rufo, J, Paciência, I, Silva, D, Martins, C, Madureira, J, Oliveira Fernandes, E, Padrão, P, Moreira, P, Delgado, L, Moreira, A
PloS one. 2018;13(3):e0193848
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Studies have shown an association between swimming in chemically-treated pools and a higher risk of asthma in children, although the mechanism is not fully understood. This study aimed to investigate how swimming pool attendance influences lung and nervous system function in school-aged children. Around 800 children were classified as current swimmers (CS), past swimmers (PS) or non-swimmers (NS). The children underwent several tests to determine their lung function and allergic response to common allergens. Parasympathetic nervous system function was tested by measuring the speed at which their pupils constricted in response to light. The current swimmers group had significantly lower pupil constriction speeds compared to PS and NS, suggesting a poorer functioning of the autonomic nervous system, possibly due to inflammation resulting from swimming pool chemical exposure. CS experienced greater constriction of the airways compared to NS. A non-significant trend for a higher risk of asthma, atopic eczema and rhinitis, was observed in swimmers. The authors concluded that swimming pool attendance appears to be associated with autonomic nervous system changes and increased baseline airway smooth muscle constriction even in children without asthma.
Abstract
BACKGROUND Endurance swimming exercises coupled to disinfection by-products exposure has been associated with increased airways dysfunction and neurogenic inflammation in elite swimmers. However, the impact of swimming pool exposure at a recreational level on autonomic activity has never been explored. Therefore, this study aimed to investigate how swimming pool attendance is influencing lung and autonomic function in school-aged children. METHODS A total of 858 children enrolled a cross sectional survey. Spirometry and airway reversibility to beta-2 agonist, skin-prick-tests and exhaled nitric oxide measurements were performed. Pupillometry was used to evaluate autonomic nervous function. Children were classified as current swimmers (CS), past swimmers (PS) and non-swimmers (NS), according to the amount of swimming practice. RESULTS Current swimmers group had significantly lower maximum and average pupil constriction velocities when compared to both PS and NS groups (3.8 and 5.1 vs 3.9 and 5.3 vs 4.0 and 5.4 mm/s, p = 0.03 and p = 0.01, respectively). Moreover, affinity to the beta-2 agonist and levels of exhaled nitric oxide were significantly higher in CS when compared to NS (70 vs 60 mL and 12 vs 10 ppb, p<0.01 and p = 0.03, respectively). A non-significant trend for a higher risk of asthma, atopic eczema and allergic rhinitis was found with more years of swimming practice, particularly in atopic individuals (β = 1.12, 1.40 and 1.31, respectively). After case-case analysis, it was possible to observe that results were not influenced by the inclusion of individuals with asthma. CONCLUSIONS Concluding, swimming pool attendance appears to be associated with autonomic changes and increased baseline airway smooth muscle constriction even in children without asthma.
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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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Fecal Microbiome and Food Allergy in Pediatric Atopic Dermatitis: A Cross-Sectional Pilot Study.
Fieten, KB, Totté, JEE, Levin, E, Reyman, M, Meijer, Y, Knulst, A, Schuren, F, Pasmans, SGMA
International archives of allergy and immunology. 2018;175(1-2):77-84
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Atopic diseases, such as atopic dermatitis (AD), asthma and rhinitis, are on the increase worldwide. Exposure to microbes may be important in the development of an atopic disease. Specifically, reduced early-life exposure is thought to be a contributing factor because microbial colonisation of the intestines during infancy plays a crucial role in the maturation of the immune system. AD, also called eczema, is an inflammatory skin disease often seen in small children. Food allergies are common in children with AD, the most common allergens being eggs, cow’s milk, peanuts, soy and wheat. This cross-sectional observational pilot study with 82 young children with a diagnosis of AD set out to identify distinct microbial patterns in the children’s faecal microbiomes associated with a clinical diagnosis of food allergy. Stool and blood samples were collected for a microbiome analysis and IgE antibody measurement, respectively. 20 children had a confirmed food allergy (most commonly to cow’s milk and peanuts), while almost half of the children without a diagnosed food allergy were sensitised to common food allergens after a food challenge. The study identified a faecal microbial signature in children with AD that differentiates between the presence and absence of food allergy. Children with AD and food allergy had more Escherichia coli and Bifidobacterium pseudocatenulatum species and less Bifidobacterium breve, Faecalibacterium prausnitzii and Akkermansia muciniphila species than children without food allergy. The authors concluded that the study supports a hypothesis that the intestinal microbiome differs in children with AD, depending on whether they have a food allergy or not. They call for future studies to confirm these findings.
Abstract
BACKGROUND Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). METHODS Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. RESULTS Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). CONCLUSIONS In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings.
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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.