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The Role of Lung and Gut Microbiota in the Pathology of Asthma.
Barcik, W, Boutin, RCT, Sokolowska, M, Finlay, BB
Immunity. 2020;52(2):241-255
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Over 300 million people suffer with asthma worldwide and it has emerged that microbiome analysis of the lung and gut bacteria, fungi, viruses, and archaea may help with disease management. This microbiome plays an important role in immune response. Disturbances to these microbes, known as dysbiosis, may influence onset of disease and the body’s ability to respond naturally, and/or to pharmaceutical treatments. Asthma is not a singular disease and there are great variations in symptom severity and underlying immune mechanisms. Patients are typically classified as type 2 or non-type 2. Type 2 patients tend to be allergic to common air-born allergens which can trigger an attack. Treatment usually consists of glucocorticosteroids or novel biologicals. Non type-2 asthma is associated with obesity-related asthma and typically responds poorly to steroid treatment. For a long time, researchers believed the human lungs to be sterile, so they were initially not included in the 2007 Human Microbiome Project. It has since been shown that, like the gut, the lungs and respiratory tract also host various microbes, and this healthy-airway microbiota influence innate and adaptive immune processes. The Gut-Lung axis also confers additional microbial benefits from the intestines. In asthma patients, there is often an over-dominance of pathogenic bacteria. Fungal dysbiosis is associated with high-risk asthma phenotypes in childhood. Viral infections have been shown as a primary cause of asthmatic episodes. Future diagnosis and treatment of patients with asthma should be assisted by analysis of the composition and metabolic activity of an individual’s microbiome.
Abstract
Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.
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A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow.
Proctor, DM, Fukuyama, JA, Loomer, PM, Armitage, GC, Lee, SA, Davis, NM, Ryder, MI, Holmes, SP, Relman, DA
Nature communications. 2018;9(1):681
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Identifying spatial patterns in the human microbiota is necessary to provide insight into mechanisms that either maintain or disrupt its healthy state. The aim of this study was to identify the type and extent of oral spatial patterns formed by bacterial communities, as well as observe the impact of low salivary flow on the spatial patterns. Dental exams were performed on 31 participants to evaluate the oral health status and follow-up was dependent on group allocation. This study found bacterial communities were distinguishable depending on types of teeth and tissue. Further, bacteria on soft and hard tissues varied across the front and back of the oral cavity in a gradient-manner, implying that salivary flow plays a role in establishing the bacterial community gradient in the oral cavity. Based on these results, the authors recommend spatial patterns and processes be explored in other body parts to better understand health and disease.
Abstract
Spatial and temporal patterns in microbial communities provide insights into the forces that shape them, their functions and roles in health and disease. Here, we used spatial and ecological statistics to analyze the role that saliva plays in structuring bacterial communities of the human mouth using >9000 dental and mucosal samples. We show that regardless of tissue type (teeth, alveolar mucosa, keratinized gingiva, or buccal mucosa), surface-associated bacterial communities vary along an ecological gradient from the front to the back of the mouth, and that on exposed tooth surfaces, the gradient is pronounced on lingual compared to buccal surfaces. Furthermore, our data suggest that this gradient is attenuated in individuals with low salivary flow due to Sjögren's syndrome. Taken together, our findings imply that salivary flow influences the spatial organization of microbial communities and that biogeographical patterns may be useful for understanding host physiological processes and for predicting disease.
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Gut microbiome: a new player in gastrointestinal disease.
Gorkiewicz, G, Moschen, A
Virchows Archiv : an international journal of pathology. 2018;472(1):159-172
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The gastrointestinal (GI) tract is colonised by millions of microorganisms, collectively called the gut microbiome. This microbiome has many biological functions including metabolism, energy regulation and communication with the immune system in the development of disease. The aim of this review was to summarise recent findings around the association between the gut microbiome and GI disease, exploring bacterial compositions, disease within the GI tract and approaches to restoring a disturbed microbiome. Recent findings support the view that the gut microbiome might serve as a future diagnostic and therapeutic target for GI disease. Based on these findings, the authors conclude that it is now evident that the human gut microbiome significantly contributes to both maintaining GI health and the development of GI disease.
Abstract
The gastrointestinal (GI) tract harbors a diverse and host-specific gut microbial community. Whereas host-microbe interactions are based on homeostasis and mutualism, the microbiome also contributes to disease development. In this review, we summarize recent findings connecting the GI microbiome with GI disease. Starting with a description of biochemical factors shaping microbial compositions in each gut segment along the longitudinal axis, improved histological techniques enabling high resolution visualization of the spatial microbiome structure are highlighted. Subsequently, inflammatory and neoplastic diseases of the esophagus, stomach, and small and large intestines are discussed and the respective changes in microbiome compositions summarized. Finally, approaches aiming to restore disturbed microbiome compositions thereby promoting health are discussed.
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The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level.
Barton, W, Penney, NC, Cronin, O, Garcia-Perez, I, Molloy, MG, Holmes, E, Shanahan, F, Cotter, PD, O'Sullivan, O
Gut. 2018;67(4):625-633
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The human gut microbiome is known to actively influence metabolism, immunity and development. It has been shown that increased physical activity and healthy diet is associated with positive changes in faecal microbial diversity and composition compared with sedentary individuals. The aim of this study was to assess the metabolic activity of the microbiota between extremely active and sedentary individuals. Metabolic and genetic factors of the gut microbiome were analysed in 40 professional rugby players and 46 sedentary controls. This study found significant differences in faecal microbiota between athletes and sedentary controls at the functional metabolic level, providing deeper insight into the link between sustained physical activity and metabolic health. Based on these results, the authors conclude exercise may be an effective way to manipulate the gut microbiome and suggest further controlled trials be done to better understand the relationship between diet, exercise and the gut microbiome.
Abstract
OBJECTIVE It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.
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The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS).
Quigley, EMM
Journal of clinical medicine. 2018;7(1)
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Irritable bowel syndrome (IBS) is a common functional gut disorder that is seen to have a number of causes. Given the widespread interest in the gut microbiome in health and disease, the role of microbiota has now been explored in the gut-brain axis paradigm. This review explores the novel addition of microbiota to the gut-brain axis and its implications to the assessment and management of IBS. Current literature suggests that a disturbed microbiome or an aberrant immune response to the disturbed microbiome may impact the central nervous system. These findings have confirmed the microbiota is useful in understanding the development of symptoms in IBS. Based on the existing literature, the author concludes there is new insight for diagnostic and therapeutic approaches to IBS.
Abstract
Irritable bowel syndrome (IBS) is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.
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A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies.
Rodiño-Janeiro, BK, Vicario, M, Alonso-Cotoner, C, Pascua-García, R, Santos, J
Advances in therapy. 2018;35(3):289-310
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Irritable bowel syndrome (IBS) is a common functional gut disorder characterised by abdominal pain and associated changes in bowel habits. Increasing evidence points to altered gut microbiota, dysbiosis, as a predominant factor in IBS development and has therefore become a primary target for therapeutic options in patients with IBS. This review evaluates existing literature on IBS interventions targeting the gut microbiota and suggests future approaches useful for diagnosis, prevention and treatment of IBS. Based on the current literature, this review suggests there is a strong role of dysbiosis in the pathophysiology of IBS. The authors conclude that there are promising therapeutic options available but further evidence is needed from larger controlled studies.
Abstract
Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain and altered bowel habit. The origin seems to be multifactorial and is still not well defined for the different subtypes. Genetic, epigenetic and sex-related modifications of the functioning of the nervous and immune-endocrine supersystems and regulation of brain-gut physiology and bile acid production and absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary and life event-related factors to enhance epithelial permeability and elicit mucosal microinflammation, immune activation and dysbiosis. Notably, strong evidence supports the role of bacterial, viral and parasitic infections in triggering IBS, and targeting microbiota seems promising in view of the positive response to microbiota-related therapies in some patients. However, the lack of highly predictive diagnostic biomarkers and the complexity and heterogeneity of IBS patients make management difficult and unsatisfactory in many cases, reducing patient health-related quality of life and increasing the sanitary burden. This article reviews specific alterations and interventions targeting the gut microbiota in IBS, including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation and other potential future approaches useful for the diagnosis, prevention and treatment of IBS.