Imperial College London

ProfessorJulianMarchesi

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Digestive Health
 
 
 
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Contact

 

+44 (0)20 3312 6197j.marchesi

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
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444 results found

Salem F, Kindt N, Marchesi JR, Netter P, Lopez A, Kokten T, Danese S, Jouzeau J-Y, Peyrin-Biroulet L, Moulin Det al., 2019, Gut microbiome in chronic rheumatic and inflammatory bowel diseases: Similarities and differences, United European Gastroenterology Journal, Pages: 205064061986755-205064061986755, ISSN: 2050-6406

<jats:sec><jats:title>Introduction</jats:title><jats:p> Inflammatory bowel diseases (IBDs) and chronic rheumatic diseases (CRDs) are systemic chronic disorders sharing common genetic, immune and environmental factors. About half of patients with IBD develop rheumatic ailments and microscopic intestinal inflammation is present in up to half of CRD patients. IBD and CRD patients also share a common therapeutic armamentarium. Disequilibrium in the complex realm of microbes (known as dysbiosis) that closely interact with the gut mucosal immune system has been associated with both IBD and CRD (spondyloarthritis and rheumatoid arthritis). Whether dysbiosis represents an epiphenomenon or a prodromal feature remains to be determined. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> In an attempt to further investigate whether specific gut dysbiosis may be the missing link between IBD and CRD in patients developing both diseases, we performed here a systematic literature review focusing on studies looking at bacterial microbiota in CRD and/or IBD patients. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> We included 80 studies, with a total of 3799 IBD patients without arthritis, 1084 CRD patients without IBD, 132 IBD patients with arthropathy manifestations and 12 spondyloarthritis patients with IBD history. Overall, this systematic review indicates that an increase in Bifidobacterium, Staphylococcus, Enterococcus, Lactobacillus, Pseudomonas, Klebsiella and Proteus genera, as well as a decrease in Faecalibacterium, Roseburia genera and species belonging to Verrucomicrobia and Fusobacteria phyla are common features in IBD and CRD patients, whereas dozens of bacterial species are specific features of CRD and IBD. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Further work is n

Journal article

Chambers E, Byrne C, Morrison D, Murphy K, Preston T, Tedford MC, Garcia Perez I, Fountana S, Serrano Contreras J, Holmes E, Roberts J, Reynolds C, Boyton R, Altmann D, McDonald J, Marchesi J, Akbar A, Riddell N, Wallis G, Frost Get al., 2019, Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial, Gut, Vol: 68, Pages: 1430-1438, ISSN: 0017-5749

Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.Design: Twelve non-diabetic adults with overweight and obesity received 20g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo controlled, crossover design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.Results: Both IPE and inulin supplementation improved insulin resistance compared to cellulose supplementation, measured by homeostatic model assessment (HOMA) 2 (Mean±SEM 1.23±0.17 IPE vs. 1.59±0.17 cellulose, P=0.001; 1.17±0.15 inulin vs. 1.59±0.17 cellulose, P=0.009), with no differences between IPE and inulin (P=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased pro-inflammatory IL-8 levels compared to cellulose, whilst inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridales) compared to cellulose, with small differences at the species level observed between IPE and cellulose. Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

Journal article

Allegretti JA, Kassam Z, Carrellas M, Mullish BH, Marchesi JR, Pechlivanis A, Smith M, Gerardin Y, Timberlake S, Pratt DS, Korzenik JRet al., 2019, Fecal microbiota transplantation in patients with primary sclerosing cholangitis: A pilot clinical trial, American Journal of Gastroenterology, Vol: 114, Pages: 1071-1079, ISSN: 1572-0241

Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed to evaluate the safety, change in liver enzymes, microbiota and metabolomic profiles in PSC patients after FMT.Methods: Open-label pilot study of PSC patients with concurrent inflammatory bowel disease (IBD) and ALP > 1.5X the upper limit of normal. Participants underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis was conducted at baseline and week 1, 4, 8, 12 and 24 post-FMT. The primaryoutcome was safety and secondary outcomes include a decrease in ALP ≥50% from baseline by week 24 post-FMT, as well as stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.Results. Ten patients underwent FMT. Nine patients had ulcerative colitis and 1 with Crohn’s colitis. The mean baseline ALP was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease ALP. The diversity increased in all patients post-FMT, as early as week 1 (p<0.01). Importantly, abundance of engrafter operational taxanomic units (OTUs) in patients post-FMT correlated with decreased ALP (p=0.02).Conclusion: To our knowledge, this first study to demonstrate that FMT in PSC is safe. Additionally, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among PSC patients.

Journal article

Ovadia C, Perdones-Montero A, Spagou K, Smith A, Sarafian MH, Gomez Romero M, Bellafante E, Clarke LC, Sadiq F, Nikolova V, Mitchell A, Dixon PH, Santa-Pinter N, Wahlström A, Abu-Hayyeh S, Walters J, Marschall H-U, Holmes E, Marchesi JR, Williamson Cet al., 2019, Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis, Hepatology, Vol: 70, Pages: 276-293, ISSN: 0270-9139

Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF)19/15 protein and mRNA levels, and 7α-hydroxy-4-cholesten-3-one. Terminal ileal farnesoid X receptor(FXR)-mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole genome sequencing and UPLC-MS were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary cholic acid supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy due to elevated bile salt hydrolase-producing Bacteroidetes. Cholic acid supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. CONCLUSION: the altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15-mediated hepatic repression of hepatic bile acid synthesis

Journal article

Ghani R, Gan C, Mullish BH, Ferizoli V, Davies F, Thursz MR, Marchesi JR, Dasgupta R, Minhas Set al., 2019, P13-2 Prevalence of recurrent Extended Spectrum Beta-Lactamase (ESBL) urinary tract infections (UTIs) in patients within a Urology service and introducing the concept of Faecal Microbiota Transplantation (FMT) as a treatment modality, British Association of Urological Surgeons Annual Scientific Meeting, Publisher: SAGE Publications, Pages: 83-85, ISSN: 2051-4158

Conference paper

Brown R, Chan D, Terzidou V, Lee Y, Smith A, Marchesi J, MacIntyre D, Bennett Pet al., 2019, Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage, BJOG: An International Journal of Obstetrics and Gynaecology, Vol: 126, Pages: 916-925, ISSN: 1470-0328

ObjectiveTo investigate the relationship between vaginal microbiota composition and outcome of rescue cervical cerclage.DesignProspective observational study.SettingQueen Charlotte’s and Chelsea Hospital, LondonPopulationTwenty singleton pregnancies undergoing a rescue cervical cerclage.MethodsVaginal microbiota composition was analysed in women presenting with a dilated cervix and exposed fetal membranes before and 10 days following rescue cervical cerclage and correlated with clinical outcomes.Main outcome measuresComposition of vaginal bacteria characterised by culture independent next generation sequencing.Successful cerclage, defined as those resulting in the birth of a neonate discharged from hospital without morbidity.Unsuccessful cerclage, defined as procedures culminating in miscarriage, intrauterine death, neonatal death or significant neonatal morbidity.ResultsReduced Lactobacillus spp. relative abundance was observed in 40% of cases prior to rescue cerclage compared to 10% of gestational age matched controls (8/20, 40% vs 3/30, 10%, P=0.017). Gardnerella vaginalis was over-represented in women presenting with symptoms (3/7, 43% vs 0/13, 0%, P=0.03, LDA (log 10) and casesculminating in miscarriage (3/6, 50% vs 0/14, 0%, P=0.017). In the majority of cases (10/14, 71%) bacterial composition was unchanged following cerclage insertionand peri-operative interventions.ConclusionsReduced relative abundance of Lactobacillus spp. is associated with premature cervical dilatation, whereas high levels of Gardnerella vaginalis are associated with unsuccessful rescue cerclage cases. The insertion of a rescue cerclage does not affect the underlying bacterial composition in the majority of cases.

Journal article

Selvarajah U, Blanco JM, Radhakrishnan S, Powles S, McDonald J, Pechlivanis A, Marchesi J, Williams H, Keat A, Machado P, Orchard Tet al., 2019, IS AXIAL SPONDYLOARTHRITIS IN IBD DIFFERENT TO AXIAL SPONDYLOARTHRITIS WITHOUT IBD?, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A96-A96, ISSN: 0017-5749

Conference paper

Selvarajah U, Blanco JM, Radhakrishnan S, Powles S, McDonald J, Pechlivanis A, Marchesi J, Keat A, Williams H, Machado P, Orchard Tet al., 2019, FAECAL CALPROTECTINSUGGESTS PRESENCE OF GUT INFLAMMATION IN AXIAL SPONDYLOARTHRITIS WITHOUT IBD, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A95-A95, ISSN: 0017-5749

Conference paper

Brown RG, Al-Memar M, Marchesi JR, Lee YS, Smith A, Chan D, Lewis H, Kindinger L, Terzidou V, Bourne T, Bennett PR, MacIntyre DAet al., 2019, Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabour rupture of the fetal membranes, Translational Research, Vol: 207, Pages: 30-43, ISSN: 1931-5244

Vaginal bacterial community composition influences pregnancy outcome. Preterm prelabor rupture of the fetal membranes (PPROM), which precedes 30% of all spontaneous preterm births, is associated with high vaginal bacterial diversity prior to rupture. The point at which vaginal bacterial diversity is established before PPROM is unknown. In this study, we use metataxonomics to longitudinally characterize the vaginal bacterial composition from as early as 6 weeks of gestation in women at high (n = 38) and low (n = 22) risk of preterm birth who subsequently experience PPROM and in women delivering at term without complications (n = 36). Reduced Lactobacillus spp. abundance and high diversity was observed prior to PPROM in 20% and 26% of women at low and high risk of preterm births respectively, but in only 3% of women who delivered at term. PPROM was associated with instability of bacterial community structure during pregnancy and a shift toward higher diversity predominately occurring during the second trimester. This was characterized by increased relative abundance of potentially pathogenic species including Prevotella, Peptoniphilus, Streptococcus, and Dialister. This study identifies reduced Lactobacillus spp. abundance and increasing vaginal bacterial diversity as an early risk factor for PPROM and highlights the need for interventional studies designed to assess the impact of modifying vaginal bacterial composition for the prevention of preterm birth.

Journal article

Allegretti JR, Kassam Z, Chiang AL, Mullish BH, Carrellas M, Hurtado J, Marchesi J, McDonald JA, Pechlivanis A, Barker GF, Blanco JM, Wong WF, Geradin Y, Silverstein M, Kennedy K, Thompson CCet al., 2019, 621 – Fecal microbiota transplantation for the treatment of obesity: A randomized, placebo-controlled pilot trial, Gastroenterology, Vol: 156, Pages: S-129-S-129, ISSN: 0016-5085

Journal article

McDonald JA, Perez JL, Mullish BH, Marchesi Jet al., 2019, Mo1953 – Growth inhibition of clostridioides difficile by short and medium chain fatty acids, Gastroenterology, Vol: 156, Pages: S-898-S-898, ISSN: 0016-5085

Journal article

Churchward MA, Michaud ER, Blanco JM, Garcia-Perez I, Mullish BH, Marchesi J, Xu H, Kao DH, Todd Ket al., 2019, Sa1924 – Effect of short chain fatty acids on gut-brain axis using a microglial cell model, Gastroenterology, Vol: 156, Pages: S-455-S-455, ISSN: 0016-5085

Journal article

Allegretti JR, Hurtado J, Carrellas M, Marcus J, Phelps E, Wong WF, Marchesi J, Mullish BH, McDonald JA, Pechlivanis A, Barker GF, Blanco JM, Sagi S, Bohm M, Kelly CR, Kassam Z, Grinspan A, Fischer Met al., 2019, 7 – The icon study: Inflammatory bowel disease and recurrent clostridium difficile infection: Outcomes after fecal microbiota transplantation, Gastroenterology, Vol: 156, Pages: S-2-S-3, ISSN: 0016-5085

Journal article

Hegade VS, Pechlivanis A, McDonald JA, Rees D, Corrigan M, Hirschfield GM, Taylor-Robinson SD, Holmes E, Marchesi JR, Kendrick S, Jones DEet al., 2019, Autotaxin, bile acid profile and effect of IBAT inhibition in primary biliary cholangitis patients with pruritus, Liver International, Vol: 39, Pages: 967-975, ISSN: 1478-3223

BACKGROUND &AIMS: Pruritus is a common symptom in patients with primary biliary cholangitis (PBC) for which ileal bile acid transporter (IBAT) inhibition is emerging as a potential therapy. We explored the serum metabonome and gut microbiota profile in PBC patients with pruritus and investigated the effect of GSK2330672, an IBAT inhibitor. METHODS: We studied fasting serum bile acids (BAs), autotaxin and faecal microbiota in 22 PBC patients with pruritus at baseline and after two weeks of GSK2330672 treatment. Control group included 31 asymptomatic PBC patients and 18 healthy volunteers. BA profiling was done by ultraperformance liquid chromatography coupled to a mass spectrometry (UPLC-MS). Faecal microbiomes were analysed by 16S ribosomal RNA gene sequencing. RESULTS: In PBC patients with pruritus serum levels of total and glyco-conjugated primary BAs and autotaxin were significantly elevated. Autotaxin activity correlated significantly with tauro- and glyco-conjugated cholic acid (CA) and chenodeoxycholic acid (CDCA), both at baseline and after GSK2330672. GSK2330672 significantly reduced autotaxin and all tauro- and glyco- conjugated BAs and increased faecal levels of CA (p=0.048) and CDCA (p=0.027). Gut microbiota of PBC patients with pruritus was similar to control groups. GSK2330672 increased relative abundance of Firmicutes (p=0.033) and Clostridia (p=0.04) and decreased Bacteroidetes (p=0.033) and Bacteroidia (p=0.04). CONCLUSIONS: Pruritus in PBC does not show a distinct gut bacterial profile but is associated with elevated serum bile acid and autotaxin levels which decrease after IBAT inhibition. In cholestatic pruritus, a complex interplay between BAs and ATX is likely and may be modified by IBAT inhibition. This article is protected by copyright. All rights reserved.

Journal article

Ghani R, Gan C, Mullish B, Ferizoli V, Thursz M, Marchesi J, Davies F, Dasgupta R, Minhas Set al., 2019, MP71-15 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., AUA 2019, Publisher: Elsevier, ISSN: 0022-5347

Conference paper

Maurice JB, Garvey L, Tsochatzis EA, Wiltshire M, Cooke G, Guppy N, McDonald J, Marchesi J, Nelson M, Kelleher P, Goldin R, Thursz M, Lemoine Met al., 2019, Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation., AIDS, Vol: 33, Pages: 805-814, ISSN: 0269-9370

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population. OBJECTIVES: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD. METHODS: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16 s rRNA sequencing was performed with stool. RESULTS: Thirty-three cases were included (≥F2 fibrosis n = 16), matched to HIV-positive (n = 29) and HIV-negative (n = 17) controls. Cases with NAFLD were more obese (BMI 31.0 ± 4.4 vs. 24.1 ± 2.8 kg/m, P < 0.001) and had significantly increased levels of sCD14, sCD163 and higher leptin to adiponectin ratio vs. HIV-positive controls. Cases with ≥F2 verses < F2 fibrosis had increased sCD14 (1.4 ± 0.4 vs. 1.1 ± 0.3 μg/ml, P = 0.023) and sCD163 (1.0 ± 0.3 vs. 0.8 ± 0.3 μg/ml, P = 0.060), which correlated with waist circumference (sCD14 P = 0.022, sCD163 P = 0.011). Immunohistochemistry showed increased hepatic portal macrophage clusters in patients with fibrosis. No markers of bacterial translocation or changes to the microbiome were associated with NAFLD or fibrosis. CONCLUSION: NAFLD fibrosis stage in HIV monoinfected patients is associated with monocyte activation in the context of obesity, which may be independent of bacterial translocation and gut microbiome.

Journal article

Ovadia C, Perdones-Montero A, Mullish B, McDonald J, Wahlstrom A, Dixon P, Walters J, Marschall H-U, Marchesi J, Williamson Cet al., 2019, Ursodeoxycholic acid treatment of cholestatic pregnancy can alter the gut microbiota to enhance bile acid modification and production of metabolically-active secondary bile acids - an explanation for 'responders' and 'non-responders'?, British Maternal & Fetal Medicine Society (BMFMS) 21st Annual Conference 2019, Publisher: WILEY, Pages: 17-17, ISSN: 1470-0328

Conference paper

Jenkins HJ, Hyde MJ, Modi N, Marchesi Jet al., 2019, An Investigation of 16S rRNA Gene Analysis Platforms for Processing Samples Acquired from Preterm Neonates., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 121A-121A, ISSN: 1933-7191

Conference paper

Ghani R, Gan C, Mullish B, Ferizoli V, Davies F, Thursz M, Marchesi J, Dasgupta R, Minhas Set al., 2019, 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., Journal of Clinical Urology

Journal article

Simon J-C, Marchesi JR, Mougel C, Selosse M-Aet al., 2019, Host-microbiota interactions: from holobiont theory to analysis, MICROBIOME, Vol: 7, ISSN: 2049-2618

Journal article

Consortium H, Drake L, Frost G, Holmes E, Lett A, Maitland K, Marchesi J, Swann J, thompson, Thompson A, Walsh Ket al., 2019, Health outcomes in Undernutrition: the role of Nutrients, Gut dysfunction and the gut microbiome (HUNGer), Health outcomes in Undernutrition: the role of Nutrients, Gut dysfunction and the gut microbiome (HUNGer), Publisher: Imperial College London

The HUNGer consortium is comprised of a multi-disciplinary, multi-national consortium of world leading researchers, with expertise in physiology and nutrition, through to clinical research, public health and agriculture in LMIC settings. The HUNGer consortium was awarded the MRC Confidence in Global Nutrition and Health award in 2018.The HUNGer consortium is developing a programme of work that will directly address United Nations Sustainable Development Goal 2 (SDG-2): End hunger, achieve food security and improve nutrition, and promote sustainable agriculture. We believe there are a number of critical unanswered questions regarding the role of the gut in undernutrition, which if answered could significantly improve the effective management and prevention of undernutrition.The following document represents the consensus opinion of the HUNGer consortium concerning the key challenges that currently limit the effective management and prevention of undernutrition and the most promising potential solutions.

Report

Segal JP, Mullish B, Quraishi MN, Acharjee A, Williams HRT, Iqbal T, Hart A, Marchesi JRet 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.

Journal article

Ghani R, Gan C, Mullish B, Ferizoli V, Davies F, Thursz M, Marchesi J, Dasgupta R, minhas Set 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

Conference paper

Moshkelgosha S, Masetti G, Berchner-Pfannschmidt U, Verhasselt HL, Horstmann M, Diaz-Cano S, Noble A, Edelman B, Covelli D, Plummer S, Marchesi JR, Ludgate M, Biscarini F, Eckstein A, Banga JPet al., 2018, Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function, HORMONE AND METABOLIC RESEARCH, Vol: 50, Pages: 932-941, ISSN: 0018-5043

Journal article

Wiggins T, Antonowicz S, Markar S, Kumar S, Adam M, Sovova K, Bodai Z, Chin S-T, Romano A, Marchesi J, Takats Z, Hanna Get al., 2018, Comprehensive Investigation of Phenol Production in Oesophagogastric Cancer - Mechanism of a Volatile Biomarker, 21st Annual Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: WILEY, Pages: 23-23, ISSN: 0007-1323

Conference paper

McDonald JAK, Mullish BH, Pechlivanis A, Liu Z, Brignardello J, Kao D, Holmes E, Li JV, Clarke TB, Thursz MR, Marchesi JRet al., 2018, Inhibiting growth of clostridioides difficile by restoring valerate, produced by the intestinal microbiota, Gastroenterology, Vol: 155, Pages: 1495-1507.e15, ISSN: 0016-5085

Background & AimsFecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth.MethodsWe used a CDI chemostat model as a tool to study the effects of FMT in vitro. The following analyses were performed: C difficile plate counts, 16S rRNA gene sequencing, 1H-NMR spectroscopy, and UPLC mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n=5) participating in an FMT trial in Canada.ResultsIn the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts (TVC) and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile TVC (94% reduction), spore counts (86% reduction), and valerate precursor concentrations—concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT, but restored after FMT. C difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid is required for germination but had no effect on vegetative growth. C difficile TVC were decreased by 95% in mice with CDI given glycerol trivalerate compared to phosphate-buffered sali

Journal article

Allegretti JR, Mullish B, Kassam Z, Carrellas M, Marchesi J, Smith M, Geradin Y, Timberlake S, Pratt D, Korzenik Jet 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 paper

Naz I, Hodgson D, Smith A, Marchesi J, Sehar S, Ahmed S, Lynch J, Avignone-Rossa C, Saroj DPet al., 2018, Investigation of the active biofilm communities on polypropylene filter media in a fixed biofilm reactor for wastewater treatment, JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, Vol: 93, Pages: 3264-3275, ISSN: 0268-2575

Journal article

Pruski P, Lewis H, Lee Y, Marchesi JR, Bennett P, Takats Z, MacIntyre DAet al., 2018, Assessment of microbiota:host interactions at the vaginal mucosa interface, Methods, Vol: 149, Pages: 74-84, ISSN: 1046-2023

There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman’s lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease.

Journal article

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