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Journal articleSegal JP, Mullish B, Quraishi MN, et al., 2019,
The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease
, Therapeutic Advances in Gastroenterology, Vol: 12, Pages: 1-13, ISSN: 1756-2848The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD.With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD.This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.
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Journal articleEyerich K, Brown S, Perez White B, et al., 2019,
Human and computational models of atopic dermatitis: a review and perspectives by an expert panel of the International Eczema Council
, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 36-45, ISSN: 0091-6749Atopic dermatitis (AD) is a prevalent disease worldwide and is associated with systemic comorbidities representing a significant burden on patients, their families, and society. Therapeutic options for AD remain limited, in part because of a lack of well-characterized animal models. There has been increasing interest in developing experimental approaches to study the pathogenesis of human AD in vivo, in vitro, and in silico to better define pathophysiologic mechanisms and identify novel therapeutic targets and biomarkers that predict therapeutic response. This review critically appraises a range of models, including genetic mutations relevant to AD, experimental challenge of human skin in vivo, tissue culture models, integration of “omics” data sets, and development of predictive computational models. Although no one individual model recapitulates the complex AD pathophysiology, our review highlights insights gained into key elements of cutaneous biology, molecular pathways, and therapeutic target identification through each approach. Recent developments in computational analysis, including application of machine learning and a systems approach to data integration and predictive modeling, highlight the applicability of these methods to AD subclassification (endotyping), therapy development, and precision medicine. Such predictive modeling will highlight knowledge gaps, further inform refinement of biological models, and support new experimental and systems approaches to AD.
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Journal articleYalchin M, Segal JP, Mullish BH, et al., 2019,
Gaps in knowledge and future directions for the use of faecal microbiota transplant in the treatment of inflammatory bowel disease
, Therapeutic Advances in Gastroenterology, Vol: 12, ISSN: 1756-2848<jats:p> Faecal microbiota transplant (FMT) has now been established into clinical guidelines for the treatment of recurrent and refractory Clostridioides difficile infection (CDI). Its therapeutic application in inflammatory bowel disease (IBD) is currently at an early stage. To date, there have been four randomized controlled trials for FMT in IBD and a multitude of observational studies. However, significant gaps in our knowledge regarding optimum methods for FMT preparation, technical aspects and logistics of its administration, as well as mechanistic underpinnings, still remain. In this article, we aim to highlight these gaps by reviewing evidence and making key recommendations on the direction of future studies in this field. In addition, we provide an overview of the current evidence of potential mechanisms of FMT in treating IBD. </jats:p>
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Conference paperGhani R, Gan C, Mullish B, et al., 2018,
Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality.
, Annual EAU Congress, Publisher: Elsevier, Pages: e375-e376, ISSN: 1569-9056 -
Journal articleCowman SA, James P, Wilson R, et al., 2018,
Profiling mycobacterial communities in pulmonary nontuberculous mycobacterial disease
, PLoS ONE, Vol: 13, ISSN: 1932-6203The diagnosis of pulmonary non-tuberculous mycobacterial disease (pNTM) is dependent on the isolation of NTM in culture, which is prone to overgrowth and contamination and may not capture the diversity of mycobacteria present, including rare or unidentified species. This study aimed to develop a culture independent method of detecting and identifying mycobacteria from sputum samples using partial sequencing of the hsp65 gene. DNA was extracted from sputum samples from subjects with pNTM and disease controls. Multiplexed partial sequencing of the hsp65 gene was performed using the Illumina MiSeq and custom primers. A reference database of hsp65 sequences was created for taxonomy assignment. Sequencing results were obtained from 42 subjects (31 cases, 11 controls). Mycobacterial sequences were identified in all subjects. In 90.5% of samples more than one species was found (median 5.5). The species isolated in culture was detected by sequencing in 81% of subjects and was the most abundant species in 62%. The sequencing of NTM from clinical samples reveals a far greater diversity than conventional culture and suggests NTM are present as communities rather than a single species. NTM were found to be present even in the absence of isolation in culture or clinical disease.
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Journal articleBrial F, Le Lay A, Dumas M-E, et al., 2018,
Implication of gut microbiota metabolites in cardiovascular and metabolic diseases
, Cellular and Molecular Life Sciences, Vol: 75, Pages: 3977-3990, ISSN: 1420-682XEvidence from the literature keeps highlighting the impact of mutualistic bacterial communities of the gut microbiota on human health. The gut microbita is a complex ecosystem of symbiotic bacteria which contributes to mammalian host biology by processing, otherwise, indigestible nutrients, supplying essential metabolites, and contributing to modulate its immune system. Advances in sequencing technologies have enabled structural analysis of the human gut microbiota and allowed detection of changes in gut bacterial composition in several common diseases, including cardiometabolic disorders. Biological signals sent by the gut microbiota to the host, including microbial metabolites and pro-inflammatory molecules, mediate microbiome–host genome cross-talk. This rapidly expanding line of research can identify disease-causing and disease-predictive microbial metabolite biomarkers, which can be translated into novel biodiagnostic tests, dietary supplements, and nutritional interventions for personalized therapeutic developments in common diseases. Here, we review results from the most significant studies dealing with the association of products from the gut microbial metabolism with cardiometabolic disorders. We underline the importance of these postbiotic biomarkers in the diagnosis and treatment of human disorders.
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Journal articleMullish BH, Quraishi MN, Segal JP, et al., 2018,
The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.
, Gut, Vol: 67, Pages: 1920-1941Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.
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Conference paperAllegretti JR, Mullish B, Kassam Z, et al., 2018,
Bile Acid Profiles are Not Altered by Fecal Microbiota Transplantation for the Treatment of Primary Sclerosing Cholangitis: Category Award (Liver): Presidential Poster Award: 1017
, ACG 2018 Meeting, Publisher: Nature Publishing Group, Pages: S574-S576, ISSN: 1572-0241 -
Conference paperGhani R, Mookerjee S, Mullish BH, et al., 2018,
Impact on Length of Stay and Antibiotic Use in Allogenic and Autologous Stem Cell Transplant Patients Colonized with Carbapenemase-producing Enterobacteriaceae
, IDWeek, Publisher: Oxford University Press, ISSN: 2328-8957 -
Journal articleHoyles L, Fernandez-Real J-M, Federici M, et al., 2018,
Publisher Correction: Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women
, Nature Medicine, Vol: 24, Pages: 1628-1628, ISSN: 1078-8956In the version of this article originally published, the received date was missing. It should have been listed as 2 January 2018. The error has been corrected in the HTML and PDF versions of this article.
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