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
to

356 results found

Koutoukidis DA, Jebb SA, Zimmerman M, Otunla A, Henry JA, Ferrey A, Schofield E, Kinton J, Aveyard P, Marchesi JRet al., 2022, The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis, GUT MICROBES, Vol: 14, ISSN: 1949-0976

Journal article

Creedon AC, Dimidi E, Hung ES, Rossi M, Probert C, Grassby T, Miguens-Blanco J, Marchesi JR, Scott SM, Berry SE, Whelan Ket al., 2022, The Impact of Almonds and Almond Processing On Gastrointestinal Physiology, Luminal Microbiology and Gastrointestinal Symptoms: a Randomized Controlled Trial and Mastication Study., Am J Clin Nutr

BACKGROUND: Almonds contain lipid, fiber and polyphenols and possess physicochemical properties that impact nutrient bioaccessibility, which are hypothesized to impact gut physiology and microbiota. OBJECTIVES: Investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition and transit time. DESIGN: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d) or an isocaloric control muffin in place of habitual snacks for 4 weeks. Gut microbiota composition and diversity (16S rRNA gene sequencing), short-chain fatty acids (gas-chromatography), volatile organic compounds (gas-chromatography mass-spectrometry), gut transit time (wireless motility capsule), stool output and gut symptoms (7-day diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured in a subgroup (n = 31). RESULTS: Modified intention-to-treat analysis was performed on 79 participants. There were no significant differences in abundance of fecal bifidobacteria following consumption of whole almonds (8.7%, SD 7.7%), ground almonds (7.8%, SD 6.9%) or control (13.0%, SD 10.2%; q = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher butyrate (24.1 μmol/g, SD 15.0 μmol/g) in comparison to control (18.2 μmol/g, SD 9.1 μmol/g; p = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency or gut symptoms. Almond form (whole versus ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher predicted lipid release (10.4%, SD 1.8%) in comparison to whole almonds (9.3%, SD 2.0%; p = 0.017). CONCLUSIONS: Almond consumption has limited impact on g

Journal article

Penney N, Yeung K, Garcia Perez I, Posma J, Kopytek A, Garratt B, Ashrafian H, Frost G, Marchesi J, Purkayastha S, Hoyles L, Darzi A, Holmes Eet al., 2022, Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity, communications medicine, ISSN: 2730-664X

Background: Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.Methods: To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity +/- T2D (n=80, T2D=42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n=27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.Results: Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.Conclusion: We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.

Journal article

Mullish BH, McDonald JAK, Marchesi JR, 2022, Mechanisms of efficacy of intestinal microbiota transplant: do not forget the metabolites, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 594-594, ISSN: 2468-1253

Journal article

Mullish BH, Martinez-Gili L, Chekmeneva E, Correia GDS, Lewis MR, Der Sluis VH-V, McDonald JAK, Pechlivanis A, Walters JRF, McClure EL, Marchesi JR, Allegretti JRet al., 2022, Fecal bile acid profiles predict recurrence in patients with primary <i>Clostridioides difficile</i> infection

<jats:label>1.</jats:label><jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Factors that influence recurrence risk in primary <jats:italic>Clostridioides difficile</jats:italic> infection (CDI) are poorly understood, and tools to predict recurrence are lacking. Perturbations in microbial-derived bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To define stool bile acid profiles and microbial bile-metabolising functionality in primary CDI patients, and explore signatures predicting recurrence.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Weekly stool samples were collected from primary CDI patients from the last day of anti-CDI therapy until recurrence, or through eight weeks post-completion otherwise. Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to profile bile acids, and bacterial bile salt hydrolase (BSH) activity was measured to determine primary BA deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in recurrers <jats:italic>versus</jats:italic> non-recurrers, and assess fecal bile acids as predictive markers for recurrence.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twenty (36%) out of 56 patients (median age 57, 64% male) recurred, with 80% of recurrence occurring within the first nine days post-antibiotic treatment. Principal component analysis (PCA) of stool bile acid profiles demonstrated clustering of samples by recurrence status and post-treatment time point. Longitudinal fecal bile acid trajectories in non-recurrers showed a recovery of secondary bile acids and their derivatives in non-r

Journal article

Whelan E, Kalliala I, Semertzidou A, Raglan O, Bowden S, Kechagias K, Markozannes G, Cividini S, McNeish I, Marchesi J, MacIntyre D, Bennett P, Tsilidis K, Kyrgiou Met al., 2022, Risk Factors for Ovarian Cancer: An Umbrella Review of the Literature, Cancers, Vol: 14, Pages: 2708-2708

<jats:p>Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.</jats:p>

Journal article

Webberley TS, Masetti G, Bevan RJ, Kerry-Smith J, Jack AA, Michael DR, Thomas S, Glymenaki M, Li J, McDonald JAK, John D, Morgan JE, Marchesi JR, Good MA, Plummer SF, Hughes TRet al., 2022, The Impact of Probiotic Supplementation on Cognitive, Pathological and Metabolic Markers in a Transgenic Mouse Model of Alzheimer's Disease, FRONTIERS IN NEUROSCIENCE, Vol: 16

Journal article

Alexander JL, Mullish BH, Danckert NP, Liu Z, Saifuddin A, Torkizadeh M, Ibraheim H, Blanco JM, Roberts LA, Bewshea CM, Nice R, Lin S, Prabhudev H, Sands C, Sluis VH-VD, Lewis M, Sebastian S, Lees CW, Teare JP, Hart A, Goodhand JR, Kennedy NA, Marchesi JR, Ahmad T, Powell Net al., 2022, The gut microbiota and metabolome is associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients

<jats:title>Abstract</jats:title> <jats:p>Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Forty-three infliximab-treated patients with IBD were recruited (30 Crohn’s disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.021). <jats:italic>Bilophila</jats:italic> abundance was associated with better serological response, while <jats:italic>Streptococcus</jats:italic> was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R<jats:sup>2</jats:sup>X 0.25, R&l

Journal article

Zhang D, Mullish BH, Wang J, Barker G, Chrysostomou D, Gao S, Chen L, McDonald JAK, Marchesi JR, Cheng Let al., 2022, Identifying transient and stable bacteria- metabolite interactions from longitudinal multi-omics data, Publisher: Research Square

BackgroundUnderstanding the complex relationships between bacteria and metabolites in ecological systems are extremely important in studies of different microbiomes. Longitudinal multi-omics study is adopted to investigate interactions between bacteria and metabolites, by directly associating their longitudinal profiles. Since a bacteria/metabolite may involve in many different biological processes, the longitudinal profile is an average of different interactions. Therefore, direct association could only uncover the strongest interactions.ResultsHere we present a computational approach that can rebuild short- and long-term bacteria-metabolite interactions from longitudinal multi-omics datasets. For this task, we re-analyse data (both microbial sequencing and metabolomic analysis) from an in vitro model of Clostridioides difficile infection and faecal microbiota transplant, a disease state and mode of therapy in which perturbed microbiome-metabolome interactions (and their reversal) are well-established to be pertinent. By analysing such a dataset, we generated both a short-term and a long-term interaction network, which predicted many new interactions. Four new interactions were randomly selected to be validated. In batch culture experiments, we validated two of them: (1) Ruminococcus gnavus and Ruminococcus luti could generate 3-ketocholanic acid (2) Blautia obeum could consume succinate.ConclusionsThe deconvolution of the raw longitudinal signal into short- and long-term trends can help users to gain a deeper understanding of their data. This tool will be useful for high-throughput screening of microbe/metabolite/host interactions from a longitudinal multi-omics setting.

Working paper

Powles STR, Gallagher KI, Chong LWL, Alexander JL, Mullish BH, Hicks LC, McDonald JAK, Marchesi JR, Williams HRT, Orchard TRet al., 2022, Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome, BMC Gastroenterology, Vol: 22, Pages: 1-9, ISSN: 1471-230X

BackgroundUrinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome.AimTo compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome.MethodsUrine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (1H NMR) spectroscopy.ResultsMicrobiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing.ConclusionsBowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea.

Journal article

Ghani R, Blanco JM, Forlano R, Triantafyllou E, Bilinski J, Geva-Zatorsky N, Bar-Yoseph H, Thursz MR, Davies F, Mullish BH, Marchesi Jet al., 2022, RELATIVE CHANGE OF ENTEROCOCCUS FAECIUM, SELECTED COMMENSAL BACTERIA AND CYTOKINES ARE SEEN IN PATIENTS COLONIZED WITH MULTIDRUG-RESISTANT ORGANISMS WHO UNDERGO INTESTINAL MICROBIOTA TRANSPLANTATION, GASTROENTEROLOGY, Vol: 162, Pages: S218-S219, ISSN: 0016-5085

Journal article

Forlano R, Mullish BH, Martinez-Gili L, Blanco JM, Liu T, Triantafyllou E, Skinner C, Thursz MR, Marchesi J, Manousou Pet al., 2022, FACTORS ASSOCIATED WITH INCREASED GUT PERMEABILITY AND SEVERITY OF LIVER DISEASE IN DIABETIC PATIENTS WITH NAFLD, GASTROENTEROLOGY, Vol: 162, Pages: S1136-S1136, ISSN: 0016-5085

Journal article

Blanco JM, Danckert NP, Liu Z, Martinez-Gili L, Mullish BH, McDonald JA, Lindsay M, Sengupta R, McHugh N, Abraham S, Marchesi Jet al., 2022, NEW LINKS BETWEEN PSORIATIC ARTHRITIS AND THE GUT MICROBIOME SUGGEST A STRONGER ROLE OF THE GUT-JOINT AXIS, GASTROENTEROLOGY, Vol: 162, Pages: S456-S457, ISSN: 0016-5085

Journal article

Blanco JM, Kragsnaes MS, Liu Z, Serrano-Contreras JI, Mullish BH, Ellingsen T, Marchesi Jet al., 2022, IMPACT ON GUT MICROBIAL METABOLITES FROM A 6-MONTH DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED TRIAL OF FECAL MICROBIOTA TRANSPLANTATION FOR ACTIVE PERIPHERAL PSORIATIC ARTHRITIS, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S829-S829, ISSN: 0016-5085

Conference paper

Alexander JL, Mullish BH, Danckert NP, Liu Z, Saifuddin A, Torkizadeh M, Ibraheim H, Blanco JM, Bewshea CM, Nice R, Lin S, Prabhudev H, Sands C, Lewis M, Teare JP, Hart A, Kennedy N, Ahmad T, Marchesi J, Powell Net al., 2022, POOR RESPONSE TO ANTI-SARS-COV-2 VACCINATION IN IMMUNOSUPPRESSED INFLAMMATORY BOWEL DISEASE PATIENTS IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, GASTROENTEROLOGY, Vol: 162, Pages: S653-S653, ISSN: 0016-5085

Journal article

Ghani R, Mullish BH, Davies FJ, Marchesi JRet al., 2022, How to adapt an intestinal microbiota transplantation program to reduce the risk of invasive multidrug-resistant infection, Clinical Microbiology and Infection, Vol: 28, Pages: 502-512, ISSN: 1198-743X

Background:Vulnerable patients with intestinal colonisation of multidrug-resistant organisms (MDROs) are recognised to be at increased risk of invasive MDRO driven infection. Intestinal Microbiota Transplantation (IMT aka FMT) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.Objectives:To describe ‘How to’ establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimising administration and assessment of endpoints.Sources:Expert guidelines and peer-reviewed clinical studies are encompassed and discussed.Content:IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) to take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT occurs when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least two weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonisation as a binary outcome. Repeat IMT is considered case-by-case.Implications:Future research areas should include randomised studies that consider clinical outcomes and cost-effectiveness, and better understa

Journal article

Ghani R, Mullish BH, Roberts L, Davies FJ, Marchesi JRet al., 2022, The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases, Gut Microbes, Vol: 14, Pages: 1-22, ISSN: 1949-0976

The intestinal microbiota is recognized to play a role in the defense against infection, but conversely also acts as a reservoir for potentially pathogenic organisms. Disruption to the microbiome can increase the risk of invasive infection from these organisms; therefore, strategies to restore the composition of the gut microbiota are a potential strategy of key interest to mitigate this risk. Fecal (or Intestinal) Microbiota Transplantation (FMT/IMT), is the administration of minimally manipulated screened healthy donor stool to an affected recipient, and remains the major ‘whole microbiome’ therapeutic approach at present. Driven by the marked success of using FMT in the treatment of recurrent Clostridioides difficile infection, he potential use of FMT in treating other infectious diseases is an area of active research. In this Review, we discuss key examples of this treatment based on recent findings relating to the interplay between microbiota and infection, and potential further exploitations of FMT/IMT.

Journal article

Martinez-Gili L, Gordon H, Blad W, McDonald JAK, Holmes E, Marchesi JR, Harbord Met al., 2022, Gut bacteria composition and familiality echo Inflammatory Bowel Disease type and pathological spectrum, 17th Congress of ECCO, Publisher: Oxford University Press, Pages: I601-I602, ISSN: 1873-9946

BackgroundInflammatory bowel disease (IBD) aetiology encompasses genetic and environmental factors. Twin studies provide valuable insights to the familial degree (shared genetics and environment) of observed phenotypes. We characterised the gut bacterial composition of twins with IBD to find taxa associated with disease and estimate their familiality.MethodsFaecal samples were collected from 88 monozygotic (MZ) and dizygotic (DZ) twin pairs concordant or discordant for Crohn’s disease (CD; 26 MZ; 19 DZ) or ulcerative colitis (UC; 16 MZ; 27 DZ). The 16S rRNA gene was sequenced and amplicon sequence variants (ASV) generated. ANCOM software was used to assess differences in IBD vs. non-IBD, stratifying by disease type (CD/UC) and adjusting for age, gender and smoking. Twin pair and zygosity were added as random effects to estimate familiality, defined as percentage of variation due to common environment and genetics. IBD-affected twins were used for differences in disease location or treatment. Participants reporting antibiotic/probiotic treatment within the last 3 months or with a stoma/pouch were not included. In UC, surgery-naive patients were compared to an excluded subset who underwent ileostomy or pouch surgery without any recent antibiotic courses.ResultsDisease concordance in MZ twins was higher in CD (54%) than UC (19%). Alpha diversity was lower in CD, but not UC, and in ileostomy and pouch vs. surgery-naive UC. Principal component analysis showed that CD-affected twins clustered apart from non-IBD ones (Figure 1A). Familiality was lower in CD, with 5% of ASVs having familiality > 50%, compared to 17% in UC (Figure 1B). Two Lachnospirales order ASVs were less abundant in UC, while 15 ASVs from Clostridia, Bacteroidia, Bacilli and Coriobacteriia classes differentiated CD from non-IBD. Firmicutes were higher in CD (β= 0.95; 95%CI [0.34,1.56]), while no phyla changed in UC. Veillonella, Barnesiella, Faecalimonas and Holdemania genera had opposite t

Conference paper

Radhakrishnan ST, Alexander JL, Mullish BH, Gallagher KI, Powell N, Hicks LC, Hart AL, Li JV, Marchesi JR, Williams HRTet al., 2022, Systematic Review: The association between the gut microbiota and medical therapies in inflammatory bowel disease, Alimentary Pharmacology and Therapeutics, Vol: 55, Pages: 26-48, ISSN: 0269-2813

BackgroundThe gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.AimsTo evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.MethodsWe conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.ResultsWe screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients.ConclusionsBoth gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

Journal article

Smith IG, Danckert NP, Freidin MB, Wells P, Marchesi JR, Williams FMKet al., 2021, Evidence for infection in intervertebral disc degeneration: a systematic review, EUROPEAN SPINE JOURNAL, Vol: 31, Pages: 414-430, ISSN: 0940-6719

Journal article

Ferreira MR, Sands CJ, Li J, Andreyev JN, Chekmeneva E, Gulliford S, Marchesi J, Lewis MR, Dearnaley DPet al., 2021, Impact of pelvic radiation therapy for prostate cancer on global metabolic profiles and microbiota-driven gastrointestinal late side effects: a longitudinal observational study, International Journal of Radiation: Oncology - Biology - Physics, Vol: 111, Pages: 1204-1213, ISSN: 0360-3016

PurposeRadiation therapy to the prostate and pelvic lymph nodes (PLNRT) is part of the curative treatment of high-risk prostate cancer. Yet, the broader influence of radiation therapy on patient physiology is poorly understood. We conducted comprehensive global metabolomic profiling of urine, plasma, and stools sampled from patients undergoing PLNRT for high-risk prostate cancer.Methods and MaterialsSamples were taken from 32 patients at 6 timepoints: baseline, 2 to 3 and 4 to 5 weeks of PLNRT; and 3, 6, and 12 months after PLNRT. We characterized the global metabolome of urine and plasma using 1H nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography-mass spectrometry, and of stools with nuclear magnetic resonance. Linear mixed-effects modeling was used to investigate metabolic changes between timepoints for each biofluid and assay and determine metabolites of interest.ResultsMetabolites in urine, plasma and stools changed significantly after PLNRT initiation. Metabolic profiles did not return to baseline up to 1 year post-PLNRT in any biofluid. Molecules associated with cardiovascular risk were increased in plasma. Pre-PLNRT fecal butyrate levels directly associated with increasing gastrointestinal side effects, as did a sharper fall in those levels during and up to 1 year postradiation therapy, mirroring our previous results with metataxonomics.ConclusionsWe showed for the first time that an overall metabolic effect is observed in patients undergoing PLNRT up to 1 year posttreatment. These metabolic changes may effect on long-term morbidity after treatment, which warrants further investigation.

Journal article

Short C-E, Quinlan R, Preda V, Wang X, Smith A, Marchesi J, Lee Y, MacIntyre D, Bennett P, Taylor Get al., 2021, Vaginal microbiota, genital inflammation and extracellular matrix remodelling collagenase: MMP-9 in pregnant women with HIV, a potential preterm birth mechanism warranting further exploration, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-14, ISSN: 2235-2988

Background: Pregnant women living with HIV infection (PWLWH) have elevated rates of preterm birth (PTB) in which HIV and cART are implicated. PWLWH also have a high prevalence of adverse vaginal microbiota, which associate with genital tract inflammation. The mechanism underlying PTB in PWLWH is unknown. We present the first data in PWLWH on genital-tract matrix-metalloproteinase-9(MMP-9), an important collagenase implicated in labour onset, and tissue inhibitor of metalloproteinases-1(TIMP-1) and explore correlations with local inflammation and vaginal bacteria. Material and Methods: Cervical vaginal fluid (CVF) collected by a soft cup and high vaginal swabs (HVS) were obtained from PWLWH and HIV uninfected pregnant women (HUPW) at three antenatal time points. Maternal characteristics, cART exposure, and pregnancy outcome were recorded. Concentrations of MMP-9, TIMP-1 and ten cytokines were measured by immunoassays. Vaginal microbiota composition was determined through 16S rRNA amplicon sequencing. MMP-9, TIMP-1 and cytokine concentrations were compared by HIV status, cART, and prematurity and in PWLWH correlations with polymorphonuclear leucocytes, cytokines and bacterial genera were explored. Results: CVF was available for 50 PWLWH (108 samples) and 12 HUPW (20 samples) between gestation weeks 14-38. Thirty-six PWLWH conceived on cART and 14 initiated post-conception. There were five and one PTB outcomes in PWLWH and HUPW respectively. PWLWH had higher mean CVF concentrations of MMP-9 (p<0.001) and TIMP-1 (p=0.035) in the second trimester compared with HUPW with a similar trend in the third trimester. PWLWH also had higher CVF values of cytokines: IL-1b, IL-8, IL-12 and TNF-a in both trimesters compared to HUPW (p≤0.003). In PWLWH, MMP-9 positively correlated with TIMP-1 (r=0.31, p=0.002) and CVF polymorphonuclear leucocytes (r=0.57, p=0.02). Correlations were observed between MMP-9 and three cytokines: IL-1b(r=0.61), IL-8(r=0.57) and TNF-a(r=0.64), p<

Journal article

Webberley TS, Masetti G, Baker LM, Dally J, Hughes TR, Marchesi JR, Jack AA, Plummer SF, Ramanathan G, Facey PD, Michael DRet al., 2021, The impact of Lab4 probiotic supplementation in a 90-day study in wistar rats, Frontiers in Nutrition, Vol: 8, Pages: 1-7, ISSN: 2296-861X

The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies in silico, in vitro, and in vivo suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol via the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.

Journal article

Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pučić-Baković M, Vučković F, Klicek F, Lauc G, Tighe P, Mullish BH, Miguens Blanco J, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Wong GK-S, Polytarchou C, Yau TO, Christodoulou N, Hatziapostoulou M, Wang M, Russell LA, Kao DHet al., 2021, A multi-factorial observational study on sequential fecal microbiota transplant in patients with medically refractory Clostridioides difficile infection, Cells, Vol: 10, ISSN: 2073-4409

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.

Journal article

Mitra A, MacIntyre DA, Paraskevaidi M, Moscicki A-B, Mahajan V, Smith A, Lee YS, Lyons D, Paraskevaidis E, Marchesi JR, Bennett PR, Kyrgiou Met al., 2021, The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia, Genome Medicine: medicine in the post-genomic era, Vol: 13, ISSN: 1756-994X

Background:Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines.Methods:We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.Results:Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment.Conclusions:Women with CIN hav

Journal article

Baker LM, Davies TS, Masetti G, Hughes TR, Marchesi JR, Jack AA, Joyce TSC, Allen MD, Plummer SF, Michael DR, Ramanathan G, Del Sol R, Facey PDet al., 2021, A genome guided evaluation of the Lab4 probiotic consortium, Genomics, Vol: 113, Pages: 4028-4038, ISSN: 0888-7543

In this study, we present the draft genome sequences of the Lab4 probiotic consortium using whole genome sequencing. Draft genome sequences were retrieved and deposited for each of the organisms; PRJNA559984 for B. bifidum CUL20, PRJNA482335 for Lactobacillus acidophilus CUL60, PRJNA482434 for Lactobacillus acid. Probiogenomic in silico analyses confirmed existing taxonomies and identified the presence putative gene sequences that were functionally related to the performance of each organism during in vitro assessments of bile and acid tolerability, adherence to enterocytes and susceptibility to antibiotics. Predictions of genomic stability identified no significant risk of horizontal gene transfer in any of the Lab4 strains and the absence of both antibiotic resistance and virulence genes. These observations were supported by the outcomes of acute phase and repeat dose tolerability studies in Wistar rats where challenge with high doses of Lab4 did not result in any mortalities, clinical/histopathological abnormalities nor indications of systemic toxicity. Detection of increased numbers of lactobacilli and bifidobacteria in the faeces of supplemented rats implied an ability to survive transit through the gastrointestinal tract and/or impact upon the intestinal microbiota composition. In summary, this study provides in silico, in vitro and in vivo support for probiotic functionality and the safety of the Lab4 consortium.

Journal article

Pruski P, Dos Santos Correia G, Lewis H, Capuccini K, Inglese P, Chan D, Brown R, Kindinger L, Lee Y, Smith A, Marchesi J, McDonald J, Cameron S, Alexander-Hardiman K, David A, Stock S, Norman J, Terzidou V, Teoh TG, Sykes L, Bennett P, Takats Z, MacIntyre Det al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, Vol: 12, ISSN: 2041-1723

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.

Journal article

Lythgoe MP, Ghani R, Mullish BH, Marchesi JR, Krell Jet al., 2021, The Potential of Faecal Microbiota Transplantation in Oncology, Trends in Microbiology, ISSN: 0966-842X

Journal article

Hansen R, Bajaj-Elliott M, Hold GL, Gerasimidis K, Iqbal TH, Amos G, Thomas LV, Marchesi JR, Gut Microbiota for Health expert panel of British Society of Gastroenterologyet al., 2021, Next-generation sequencing as a clinical laboratory tool for describing different microbiotas: an urgent need for future paediatric practice., Arch Dis Child, Vol: 106

Journal article

Mitra A, MacIntyre D, Paraskevaidi M, Moscicki A-B, Mahajan V, Smith A, Lyons D, Paraskevaidis E, Marchesi J, Bennett P, Kyrgiou Met al., 2021, The vaginal microbiota and innate Immunity after local excisional treatment for cervical intraepithelial neoplasia, Publisher: BioMed Central

Background: Vaginal microbiota (VMB) are altered in women with cervical intra-epithelial neoplasia (CIN) and associate with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This interventional study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMPs levels in matched vaginal secretions. Analyses were performed to compare bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.Results: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV: 21/103, 20% vs 1/39, 3%, p=0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV: 19/103, 20% vs 1/39, 3%, p=0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1 and IL-8 remained significantly elevated pre- (p<0.0001 and p=0.0014 respectively) and post-treatment compared to untreated controls (p<0.0001 and p=0.0035 respectively). Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p<0.0001), however their levels remained lower than controls post-treatment.Conclusions: Women with CIN have increased prevalence of Lactobacillus spp. depleted, high-diversity V

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