Publications
110 results found
Akhbari P, Jaggard MK, Boulange CL, et al., 2021, Differences between infected and noninfected synovial fluid, BONE & JOINT RESEARCH, Vol: 10, Pages: 85-95, ISSN: 2046-3758
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- Citations: 3
Innes AJ, Ghani R, Mullish BH, et al., 2020, O105. Faecal microbiota transplant (FMT) can reduce the high NRM associated with multi-drug resistant organism (MDRO) colonisation prior to allogeneic HCT., The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Springer Nature [academic journals on nature.com], Pages: 122-122, ISSN: 0268-3369
Jaggard MKJ, Boulange CL, Graca G, et al., 2020, Can metabolic profiling provide a new description of osteoarthritis and enable a personalised medicine approach?, CLINICAL RHEUMATOLOGY, Vol: 39, Pages: 3875-3882, ISSN: 0770-3198
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- Citations: 4
Martinez-Gili L, McDonald JAK, Liu Z, et al., 2020, Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial derived metabolites, Gut Microbes, Vol: 12, ISSN: 1949-0976
Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.
Ghani R, Mullish BH, McDonald JA, et al., 2020, 1144 FECAL MICROBIOTA TRANSPLANT FOR MULTI-DRUG RESISTANT ORGANISMS: IMPROVED CLINICAL OUTCOMES BEYOND INTESTINAL DECOLONISATION, Publisher: Elsevier BV, ISSN: 0016-5085
Akhbari P, Karamchandani U, Jaggard MKJ, et al., 2020, Can joint fluid metabolic profiling (or "metabonomics") reveal biomarkers for osteoarthritis and inflammatory joint disease? A SYSTEMATIC REVIEW, BONE & JOINT RESEARCH, Vol: 9, Pages: 108-119, ISSN: 2046-3758
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- Citations: 17
Ghani R, Mullish BH, McDonald J, et al., 2020, Disease prevention not decolonisation: a cohort study for faecal microbiota transplantation for patients colonised with multidrug-resistant organisms, ECCMID 2020
Barry R, Ruano-Gallego D, Radhakrishnan ST, et al., 2020, Faecal neutrophil elastase-antiprotease balance reflects colitis severity, Mucosal Immunology, Vol: 13, Pages: 322-333, ISSN: 1933-0219
Given the global burden of diarrheal diseases on healthcare it is surprising how little is known about the drivers of disease severity. Colitis caused by infection and inflammatory bowel disease (IBD) is characterised by neutrophil infiltration into the intestinal mucosa and yet our understanding of neutrophil responses during colitis is incomplete. Using infectious (Citrobacter rodentium) and chemical (dextran sulphate sodium; DSS) murine colitis models, as well as human IBD samples, we find that faecal neutrophil elastase (NE) activity reflects disease severity. During C. rodentium infection intestinal epithelial cells secrete the serine protease inhibitor SerpinA3N to inhibit and mitigate tissue damage caused by extracellular NE. Mice suffering from severe infection produce insufficient SerpinA3N to control excessive NE activity. This activity contributes to colitis severity as infection of these mice with a recombinant C. rodentium strain producing and secreting SerpinA3N reduces tissue damage. Thus, uncontrolled luminal NE activity is involved in severe colitis. Taken together, our findings suggest that NE activity could be a useful faecal biomarker for assessing disease severity as well as therapeutic target for both infectious and chronic inflammatory colitis.
Akhbari P, Jaggard MK, Boulange CL, et al., 2019, Differences in the composition of hip and knee synovial fluid in osteoarthritis: a nuclear magnetic resonance (NMR) spectroscopy study of metabolic profiles, OSTEOARTHRITIS AND CARTILAGE, Vol: 27, Pages: 1768-1777, ISSN: 1063-4584
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- Citations: 5
Mullish BH, McDonald JAK, Pechlivanis A, et al., 2019, Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection, Gut, Vol: 68, Pages: 1791-1800, ISSN: 0017-5749
Objective Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT’s efficacy in treating the condition.Design Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh/baiCD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI.Results From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh/baiCD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh-expressing E. coli and naturally BSH-producing organisms (Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05).Conclusion Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.
Mullish BH, 2019, The role of bile-metabolising enzymes in the pathogenesis of Clostridioides difficile infection, and the impact of faecal microbiota transplantation
Powles STR, Chong LW, Gallagher KI, et al., 2019, EFFECT OF ETHNICITY ON THE FAECAL WATER METABOLIC PROFILES IN CROHN'S DISEASE, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A90-A91, ISSN: 0017-5749
Powles STR, Gallagher K, Hicks LC, et al., 2019, EFFECT OF CO-MORBIDITIES IN CROHN'S DISEASE ASSOCIATED URINARY METABOLIC PROFILES, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A89-A90, ISSN: 0017-5749
Jaggard MKJ, Boulange CL, Akhbari P, et al., 2019, A systematic review of the small molecule studies of osteoarthritis using nuclear magnetic resonance and mass spectroscopy, OSTEOARTHRITIS AND CARTILAGE, Vol: 27, Pages: 560-570, ISSN: 1063-4584
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- Citations: 11
Segal 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: 1756-2848
The 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.
Mullish BH, Quraishi MN, Segal J, 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: 1920-1941, ISSN: 0017-5749
Interest 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 United Kingdom (UK) have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. Whilst 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.
Mullish BH, Quraishi MN, Segal J, et al., 2018, Introduction to the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) faecal microbiota transplant guidelines, Journal of Hospital Infection, Vol: 100, Pages: 130-132, ISSN: 0195-6701
Mullish 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, Journal of Hospital Infection, Vol: 100, Pages: S1-S31, ISSN: 0195-6701
Interest 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 United Kingdom (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.
Stevenson H, Parkes M, Austin L, et al., 2018, The development of a small-scale wear test for CoCrMo specimens with human synovial fluid, Biotribology, Vol: 14, Pages: 1-10, ISSN: 2352-5738
A new test was developed to measure friction and wear of hip implant materials under reciprocating sliding conditions. The method requires a very small amount of lubricant (<3 ml) which allows testing of human synovial fluid. Friction and wear of Cobalt Chromium Molybdenum (CoCrMo) material pairs were measured for a range of model and human synovial fluid samples. The initial development of the test assessed the effect of fluid volume and bovine calf serum (BCS) concentration on friction and wear. In a second series of tests human synovial fluid (HSF) was used. The wear scar size (depth and volume) on the disc was dependent on protein content and reduced significantly for increasing BCS concentration. The results showed that fluid volumes of <1.5 ml were affected by evaporative loss effectively increasing the protein concentration resulting in anomalously lower wear. At the end of the test thick deposits were observed in and around the wear scars on the disc and ball; these were analysed by Infrared Reflection-Absorption Spectroscopy. The deposits were composed primarily of denatured proteins and similar IR spectra were obtained from the BCS and HSF tests. The analysis confirmed the importance of SF proteins in determining wear of CoCrMo couples.
Mullish BH, Williams HRT, 2018, Clostridium difficile infection and antibiotic-associated diarrhoea., Clinical Medicine, Vol: 18, Pages: 237-241, ISSN: 1470-2118
Antibiotic-associated diarrhoea is amongst the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have given new insights into the pathogenesis of these conditions, as well as revealing a role for manipulation of the gut microbiota as a novel therapeutic approach. This CME review will give an overview of assessment of these conditions, before particularly focusing on the rapidly-developing area of their treatment.
Powles ST, Hicks LC, Chong LW, et al., 2018, EFFECT OF BOWEL PURGATIVES ON URINARY METABOLIC PROFILING ASSOCIATED WITH THE FAECAL MICROBIOME, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week (DDW) / 59th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S860-S860, ISSN: 0016-5085
Powles ST, Chong LW, Cameron S, et al., 2018, THE USE OF RAPID EVAPORATIVE IONISATION MASS SPECTROMETRY (REIMS) IN FAECAL SAMPLES TO IDENTIFY INFLAMMATORY BOWEL DISEASE, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S396-S396, ISSN: 0016-5085
King A, Mullish B, Williams H, et al., 2017, Comparative epidemiology of Clostridium difficile infection in England and the US, International Journal for Quality in Health Care, Vol: 29, Pages: 785-791, ISSN: 1353-4505
Objective: To examine whether there is an epidemiological difference between Clostridium difficile infection (CDI) inpatient populations in England and the United States.Design: A cross-sectional study.Setting: National administrative inpatient discharge data from England (Hospital Episode Statistics) and the United States (National Inpatient Sample) in 2012.Participants: De-identifiable non-obstetric inpatient discharges from the national datasets were used to estimate national CDI incidence in the United States and England using ICD9-CM(008.45) and ICD10(A04.7) respectively. Main outcome measures: The rate of CDI was calculated per 100,000 population using national population estimates. Rate per 100,000 inpatient discharges was also calculated separated by primary and secondary diagnosis of CDI. Age, sex and Elixhauser comorbidities profiles were examined. Results: The US had a higher rate of CDI compared to England: 115.1/100,000 vs. 19.3/100,000 population (p<0.001). CDI age profiles differed between the countries (p<0.001): in England, patients ≥75years constitute a larger proportion of CDI cases, whilst those aged 25-70 constitute more cases in the US(p<0.001). Overall adjusted odds of CDI in females compared to males was elevated in both England (OR1.26 95%CI[1.21,1.31] p<0.001) and the US (OR1.20 95%CI[1.18,1.22] p<0.001). The proportion of CDI patients with comorbidities was greater in the US compared to England apart from dementia, which was greater in England (9.63% vs. 1.25%,p<0.0001).Conclusions: The 2012 inpatient CDI rate within the US was much higher than in England. Age and co-morbidity profiles also differed between CDI patients in both countries. The reasons for this are likely multi-factorial but may reflect national infection control policy.
Williams HRT, Orchard TR, 2017, Volatile organic compounds in breath for monitoring IBD - longitudinal studies are essential, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 46, Pages: 371-372, ISSN: 0269-2813
Chong LWL, Powles STR, Hicks LC, et al., 2017, ASSESSING THE INDIVIDUAL RISK OF ACUTE SEVERE COLITISAT DIAGNOSIS IN A SOUTH ASIAN POPULATION, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A150-A151, ISSN: 0017-5749
Hicks LC, Powles STR, Chong LWL, et al., 2017, EFFECTS OF TIME ON URINARY METABOLIC SIGNATURES IN INFLAMMATORY BOWEL DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A233-A234, ISSN: 0017-5749
Hicks LC, Powles STR, Chong LWL, et al., 2017, ASSESSING THE EFFECT OF ETHNICITY ON URINARY METABOLIC PROFILES IN INFLAMMATORY BOWEL DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A261-A262, ISSN: 0017-5749
Mullish BH, McDonald JAK, Kao DH, et al., 2017, OC-063 Gut microbiota-host bile acid metabolism interactions in clostridium difficile infection: the explanation for the efficacy of faecal microbiota transplantation?, British Society of Gastroenterology Annual Meeting, Publisher: BMJ Publishing Group, Pages: A33-A34, ISSN: 1468-3288
Mullish BH, McDonald J, Kao DH, et al., 2017, Understanding the mechanisms of efficacy of fecal microbiota transplantation in the treatment of Clostridium difficile Infection: the potential role of bile metabolising enzymes, Digestive Diseases Week, Publisher: Elsevier, Pages: S47-S47, ISSN: 0016-5085
Hicks LC, Powles ST, Swann JR, et al., 2017, EFFECTS OF TIME ON URINARY METABOLIC SIGNATURES IN INFLAMMATORY BOWEL DISEASE, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S611-S612, ISSN: 0016-5085
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