Imperial College London

DrHoraceWilliams

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3312 1208h.williams

 
 
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Location

 

GI UnitClarence WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

109 results found

Mullish BH, Bak A, Merrick B, Quraishi MN, Goldenberg SD, Williams HRTet al., 2024, Overview of the second edition of the joint British Society of Gastroenterology and Healthcare Infection Society faecal microbiota transplant guidelines, 2024, Journal of Hospital Infection, ISSN: 0195-6701

Journal article

Mullish BH, Merrick B, Quraishi MN, Bak A, Green CA, Moore DJ, Porter RJ, Elumogo NT, Segal JP, Sharma N, Marsh BL, Kontkowski G, Manzoor SE, Hart AL, Settle C, Keller JJ, Hawkey P, Iqbal TH, Goldenberg SD, Williams HRTet al., 2024, The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines, Gut, ISSN: 0017-5749

Journal article

Mullish BH, Merrick B, Quraishi MN, Bak A, Green CA, Moore DJ, Porter RJ, Elumogo NT, Segal JP, Sharma N, Marsh BL, Kontkowski G, Manzoor SE, Hart AL, Settle C, Keller JJ, Hawkey P, Iqbal TH, Goldenberg SD, Williams HRTet al., 2024, The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines, Journal of Hospital Infection, ISSN: 0195-6701

Journal article

Perry R, Mummery D, Alexander J, Hicks L, Williams Het al., 2024, Faecal Calprotectin in Primary Care – Is Its Current Use Supported by the Evidence?, British Journal of General Practice, ISSN: 0960-1643

Journal article

Liu Z, Alexander J, Eng K, Ibraheim H, Anandabaskaran S, Saifuddin M, Constable L, Castro Seoane R, Balarajah S, Hicks L, Williams H, Teare J, Altmann D, Boyton R, Pollock K, Hart A, Powell Net al., 2023, Antibody responses to Influenza vaccination are diminished in patients with inflammatory bowel disease on infliximab or tofacitinib, Journal of Crohn's and Colitis, ISSN: 1873-9946

Background and aims:We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with IBD.Methods:We conducted a prospective study including 213 IBD patients and 53 healthy controls; 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination and interval between vaccination and sampling.Results:Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (Geometric Mean Ratio 0.35 [95% CI 0.20-0.60], p=0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p=0.0050) and tofacitinib (0.28 [0.14-0.57], p=0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p=0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p=0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p=0.017) and tofacitinib (0.23 [0.10-0.56], p=0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 (r=0.27; p=0.0004) and H1N1 (r=0.33; p<0.0001).Conclusions:Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to Influenza/A, similar to COVID-19 vaccine-induced antibody responses. Funding:Financial support was

Journal article

Liu Z, Alexander J, Le K, Zhou X, Ibraheim H, Anandabaskaran S, Saifuddin M, LIN K, Leon M, Constable L, Castro Seoane R, Anand N, Bewshea C, Nice R, D'Mello A, Jones G, Balarajah S, Fiorentino F, Sebastian S, Irving P, Hicks LC, Williams HRT, Kent A, Linger R, Parkes M, Klaartje K, Patel K, Teare JP, Altmann DM, Boyton RJ, Hart AL, Lees C, Goodhand J, Kennedy N, Pollock K, Ahmad T, Powell Net al., 2023, Neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 and wild-type virus in patients with inflammatory bowel disease following three doses of COVID-19 vaccine (VIP): a prospective, multicentre, cohort study, EClinicalMedicine, Vol: 64, ISSN: 2589-5370

BackgroundPatients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant.MethodsIn this multicentre cohort study, we prospectively recruited 340 adults (69 healthy controls and 271 IBD) at nine UK hospitals between May 28, 2021 and March 29, 2022. The IBD study population was established (>12 weeks therapy) on either thiopurine (n = 63), infliximab (n = 45), thiopurine and infliximab combination therapy (n = 48), ustekinumab (n = 45), vedolizumab (n = 46) or tofacitinib (n = 24). Patients were excluded if they were being treated with any other immunosuppressive therapies. Participants had two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccines, followed by a third dose of either BNT162b2 or mRNA1273. Pseudo-neutralisation assays against SARS-CoV-2 wild-type and BA.4/5 were performed. The half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type virus and Omicron BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type, age, and interval between vaccination and blood collection. This study is registered with ISRCTN (No. 13495664).FindingsBoth heterologous (first two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both wild-type SARS-CoV-2 virus and the Omicron BA.4/5 variant in healthy participants and patients with IBD. Antibody titres against BA.4/5 were significantly lower than antibodies against wild-type virus in both healthy participants and patients with IBD (p < 0.0001). Multivariable models demonstrated that neutralising antibodies against

Journal article

Jaggard MKJ, Boulange CL, Graca G, Akhbari P, Vaghela U, Bhattacharya R, Williams HRT, Lindon JC, Gupte CMet al., 2023, The effect of liquid-liquid extraction on metabolite detection and analysis using NMR spectroscopy in human synovial fluid, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 226, ISSN: 0731-7085

Journal article

Radhakrishnan ST, Gallagher KI, Mullish BH, Serrano Contreras JI, Alexander JL, Miguens Blanco J, Danckert NP, Valdivia Garcia M, Hopkins BJ, Ghai A, Ayub A, Li JV, Marchesi JR, Williams HRTet al., 2023, Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition, Scientific Reports, Vol: 13, Pages: 1-9, ISSN: 2045-2322

Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota’s functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson’s coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites, with overall excellent correlation identified between rectal swab and faecal samples for levels all metabolites collectively, although more variable degrees of association between swab and stool for levels of individual metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.

Journal article

Valdivia-Garcia MA, Chappell KE, Camuzeaux S, Olmo-Garcia L, van der Sluis VH, Radhakrishnan ST, Stephens H, Bouri S, Braz LMDC, Williams HT, Lewis MR, Frost G, Li Jet al., 2022, Improved quantitation of short-chain carboxylic acids in human biofluids using 3-nitrophenylhydrazine derivatization and liquid chromatography with tandem mass spectrometry (LC-MS/MS), JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 221, ISSN: 0731-7085

Journal article

Alexander J, Liu Z, Munoz Sandoval D, Reynolds C, Ibraheim H, Saifuddin M, Constable L, Altmann D, Balarajah S, Hicks L, Williams H, Teare J, Hart A, Boyton R, Powell Net al., 2022, COVID-19 vaccine-induced antibody and T cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose: a multicentre, prospective, case-control study, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 1005-1015, ISSN: 2468-1253

Background:COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to determine whether immunosuppressive treatments were associated with reduced antibody and T cell responses after a third vaccine dose.Methods:352 adults (72 healthy controls and 280 IBD) were sampled 28-49 days after a third dose of SARS-CoV-2 vaccine. IBD medications studied included thiopurines (n=65), infliximab (n=46), thiopurine/infliximab combination therapy (n=49), ustekinumab (n=44), vedolizumab (n=50) or tofacitinib (n=26). SARS-CoV-2 spike antibody binding and T cell responses were measured. Findings:Geometric mean [geometric SD] anti-S1 RBD antibody concentrations increased in all groups following a third dose, but were significantly lower in patients treated with infliximab (2736.8 U/mL [4.3]; P<0.0001), infliximab and thiopurine combination (1818.3 U/mL [6.7]; P<0.0001) and tofacitinib (8071.5 U/mL [3.1]; P=0.0018) compared to controls (16774.2 U/ml [2.6]). There were no significant differences in anti-S1 RBD antibody concentrations between control subjects and thiopurine (12019.7 U/mL [2.2]; P=0.099), ustekinumab (11089.3 U/mL [2.8]; P=0.060), nor vedolizumab treated patients (13564.9 U/mL [2.4]; P=0.27). In multivariable modelling, lower anti-S1 RBD antibody concentrations were independently associated with infliximab (Geometric mean ratio 0.15, 95% CI 0.11-0.21, P<0.0001), tofacitinib (0.52, 95% CI 0.31-0.87, P=0.012) and thiopurine (0.69, 95% CI 0.51-0.95, P=0.021), but not with ustekinumab (0.64, 95% CI 0.39-1.06, P=0.083), or vedolizumab (0.84, 95% CI 0.54-1.30, P=0.43). Previous SARS-CoV-2 infection (1.58, 95% CI 1.22-2.05, P=0.00056) and older age (0.88, 95% CI 0.80-0.97, P=0.0073) were independently associated with higher and lower anti-S1 antibody concentrations respectively. Antigen specific T cell responses were similar in all groups, except for reci

Journal article

Alexander JL, Liu Z, Mūnoz Sandoval D, Reynolds C, Ibraheim H, Anandabaskaran S, Saifuddin A, Castro Seoane R, Anand N, Nice R, Bewshea C, D'Mello A, Constable L, Jones G, Balarajah S, Fiorentino F, Sebastian S, Irving P, Hicks L, Williams HRT, Kent A, Linger R, Parkes M, Kok K, Patel K, Teare JP, Altmann D, Goodhand J, Hart A, Lees C, Boyton RJ, Kennedy NA, Ahmad T, Powell N, Investigators VIPSet al., 2022, COVID-19 vaccine-induced antibody and T cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose, Publisher: SSRN

Background: COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking infliximab or tofacitinib after two vaccine doses. We sought to determine whether immunosuppressive treatments were associated with reduced antibody and T cell responses after a third vaccine dose. Methods: 352 adults (72 healthy controls and 280 IBD) from the prospectively recruited study cohort were sampled 28-49 days after a third dose of SARS-CoV-2 vaccine. IBD medications studied included thiopurines (n=65), infliximab (n=46), thiopurine/infliximab combination therapy (n=49), ustekinumab (n=44), vedolizumab (n=50) or tofacitinib (n=26). SARS-CoV-2 spike antibody binding and T cell responses were measured. Findings: Geometric mean [geometric SD] anti-S1 RBD antibody concentrations increased in all study groups following a third dose of vaccine, but were significantly lower in patients treated with infliximab (2736.8 U/mL [4.3]; P<0.0001), infliximab and thiopurine combination (1818.3 U/mL [6.7]; P<0.0001) and tofacitinib (8071.5 U/mL [3.1]; P=0.0018) compared to controls (16774.2 U/ml [2.6]). There were no significant differences in anti-S1 RBD antibody concentrations between control subjects and thiopurine (12019.7 U/mL [2.2]; P=0.099), ustekinumab (11089.3 U/mL [2.8]; P=0.060), nor vedolizumab treated patients (13564.9 U/mL [2.4]; P=0.27). In multivariable modelling, lower anti-S1 RBD antibody concentrations were independently associated with infliximab (Geometric mean ratio 0.15, 95% CI 0.11-0.21, P<0.0001), tofacitinib (0.52, 95% CI 0.31-0.87, P=0.012) and thiopurine (0.69, 95% CI 0.51-0.95, P=0.021), but not with ustekinumab (0.64, 95% CI 0.39-1.06, P=0.083), or vedolizumab (0.84, 95% CI 0.54-1.30, P=0.43). Previous SARS-CoV-2 infection (1.58, 95% CI 1.22-2.05, P=0.00056) and older age (0.88, 95% CI 0.80-0.97, P=0.0073) were independently associated with higher and lower anti-S1 antibody concentrations respectively. However

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

Alexander JL, Kennedy N, Ibraheim H, Anandabaskaran S, Saifuddin A, Seoane RC, Liu Z, Nice R, Bewshea CM, D'Mello A, Constable LE, Jones G-R, Balarajah S, Fiorentino F, Sebastian S, Irving PM, Hicks LC, Williams HR, Kent AJ, Parkes M, Kok K, Patel KV, Altmann D, Boyton R, Goodhand J, Hart A, Lees CW, Ahmad T, Powell Net al., 2022, COVID-19 VACCINE-INDUCED ANTIBODY RESPONSES ARE IMPAIRED IN IBD PATIENTS TREATED WITH INFLIXIMAB, USTEKINUMAB OR TOFACITINIB, BUT NOT THIOPURINES OR VEDOLIZUMAB, Publisher: W B SAUNDERS CO-ELSEVIER INC

Working paper

Alexander JL, Kennedy NA, Ibraheim H, Anandabaskaran S, Saifuddin A, Castro Seoane R, Liu Z, Nice R, Bewshea C, D'Mello A, Constable L, Jones GR, Balarajah S, Fiorentino F, Sebastian S, Irving PM, Hicks LC, Williams HRT, Kent AJ, Linger R, Parkes M, Kok K, Patel KV, Teare JP, Altmann DM, Boyton RJ, Goodhand JR, Hart AL, Lees CW, Ahmad T, Powell N, VIP study investigatorset al., 2022, COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 342-352, ISSN: 2468-1253

BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·

Journal article

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

Moore-Gillon C, Suleiman S, Mullish BH, Williams HRTet al., 2021, Faecal microbiota transplant in the treatment of Clostridioides difficile infection: an update, European Medical Journal Gastroenterology, Vol: 10, Pages: 60-68, ISSN: 2054-6203

Clostridioides difficile infection (CDI) presents a major global healthcare challenge. Recurrent/refractory disease is particularly hard to manage, and novel therapeutic strategies have recently been adopted. In particular, within the past decade, faecal microbiota transplant (FMT) has rapidly progressed from a “potential” treatment option of fringe interest to one of the mainstays of therapy for recurrent/refractory C. difficile infection (rCDI). The first randomised study of its use for this indication was published as recently as 2013, but the emergence of subsequent randomised studies has led to its rapid adoption into guidelines and treatment algorithms. Very rare but serious reports of infection transmission from donor to recipient have resulted in ongoing refinements to donor screening, including the adoption of routine screening for intestinal carriage of multi-drug resistant bacteria and SARS-CoV-2 status. Developments in the evidence base have given new insights into optimal recipient selection and preparation. Upper and lower gastrointestinal administration of FMT slurry are both safe and effective in treating rCDI, although the newer option of capsulised FMT has recently grown in popularity; ‘next generation’ FMT products of defined microbial communities derived from donor stool are in late phase clinical trials, and may become licensed for use in the near future. While different regulatory structures for FMT use have been adopted in different countries, the development of international networks of FMT-interested specialists has helped to harmonise best practice.

Journal article

Baunwall SMD, Terveer EM, Dahlerup JF, Erikstrup C, Vehreschild MJGT, Ianiro G, Gasbarrini A, Sokol H, Kump PK, Satokari R, De Looze D, Vermeire S, Nakov R, Brezina J, Helms M, Kjeldsen J, Rode AA, Kousgaard SJ, Alric L, Trang-Poisson C, Scanzi J, Link A, Stallmach A, Kupcinskas J, Johnsen PH, Garborg K, Sánchez-Rodríguez E, Serrander L, Brummer RJ, Galpérine KT, Goldenberg SD, Mullish BH, Williams HRT, Iqbal TH, Ponsioen C, Kuijper EJ, Cammarota G, Keller JJ, Hvas CLet al., 2021, The use of faecal microbiota transplantation (FMT) in Europe: a Europe-wide survey, The Lancet Regional Health - Europe, Vol: 9, ISSN: 2666-7762

BackgroundFaecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.MethodsWe invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.FindingsIn 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10–64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100–28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.InterpretationFMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.FundingNordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056–00006B).

Journal article

Innes AJ, Mullish BH, Ghani R, Szydlo RM, Apperley JF, Olavarria E, Palanicawandar R, Kanfer EJ, Milojkovic D, McDonald JAK, Brannigan ET, Thursz MR, Williams HRT, Davies FJ, Marchesi JR, Pavlu Jet al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT).This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis to non-MDRO colonized control cohorts(2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.

Journal article

Gallagher K, Catesson A, Griffin JL, Holmes E, Williams HRTet al., 2021, Metabolomic analysis in inflammatory bowel disease: a systematic review, Journal of Crohns & Colitis, Vol: 15, Pages: 813-826, ISSN: 1873-9946

BACKGROUND AND AIMS: The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are chronic, idiopathic gastrointestinal (GI) diseases. Whilst their precise etiology is unknown, it is thought to involve a complex interaction between genetic predisposition and an abnormal host immune response to environmental exposures, likely microbial. Microbial dysbiosis has frequently been documented in IBD. Metabolomics (the study of small molecular intermediates and end products of metabolism in biological samples) provides a unique opportunity to characterize disease-associated metabolic changes and may be of particular use in quantifying gut microbial metabolism. Numerous metabolomic studies have been undertaken in inflammatory bowel disease populations, identifying consistent alterations in a range of molecules across several biological matrices. This systematic review aims to summarize these findings. METHODS: A comprehensive, systematic search was carried out using Medline and EMBASE. All studies were reviewed by two authors independently using predefined exclusion criteria. A total of sixty-four relevant papers were quality assessed and included in the review. RESULTS: Consistent metabolic perturbations were identified, including increases in levels of branched chain amino acids and lipid classes across stool, serum, plasma and tissue biopsy samples, and reduced levels of microbially modified metabolites in both urine (such as hippurate) and stool (such as secondary bile acids). CONCLUSIONS: This review provides a summary of metabolomic research in IBD to date, highlighting underlying themes of perturbed gut microbial metabolism and mammalian-microbial co-metabolism associated with disease status.

Journal article

Mullish BH, Innes AJ, Ghani R, Szydlo R, Williams HR, Thursz MR, Marchesi J, Davies F, Pavlu Jet al., 2021, FECAL MICROBIOTA TRANSPLANT PRIOR TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT IN PATIENTS COLONIZED WITH MULTI-DRUG RESISTANT ORGANISMS IS ASSOCIATED WITH IMPROVED SURVIVAL, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S168-S169, ISSN: 0016-5085

Conference paper

Radhakrishnan ST, Vasireddy A, Gallagher KI, Hicks LC, Powles ST, Chong L, Peake ST, Orchard TR, Williams HRTet al., 2021, Long-term follow up in IBD: 10-year observational study of a UK IBD cohort, Publisher: OXFORD UNIV PRESS, Pages: S588-S588, ISSN: 1873-9946

Conference paper

Radhakrishnan ST, Mullish BH, Gallagher K, Alexander JL, Danckert NP, Blanco JM, Serrano-Contreras JI, Valdivia-Garcia M, Hopkins BJ, Ghai A, Li JV, Marchesi J, Williams HRet al., 2021, RECTAL SWABS AS A VIABLE ALTERNATIVE TO FECAL SAMPLING FOR THE ANALYSIS OF GUT MICROBIOME FUNCTIONALITY AS WELL AS COMPOSITION, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S733-S733, ISSN: 0016-5085

Conference paper

Ghani R, Mullish BH, McDonald JAK, Ghazy A, Williams HRT, Brannigan ET, Mookerjee S, Satta G, Gilchrist M, Duncan N, Corbett R, Innes AJ, Pavlu J, Thursz MR, Davies F, Marchesi JRet al., 2021, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, Vol: 72, Pages: 1444-1447, ISSN: 1058-4838

Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.

Journal article

Jaggard MKJ, Boulange CL, Graca G, Akhbari P, Vaghela U, Bhattacharya R, Williams HRT, Lindon JC, Gupte CMet al., 2021, The influence of sample collection, handling and low temperature storage upon NMR metabolic profiling analysis in human synovial fluid, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 197, ISSN: 0731-7085

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Keller JJ, Ooijevaar RE, Hvas CL, Terveer EM, Lieberknecht SC, Hogenauer C, Arkkila P, Sokol H, Gridnyev O, Megraud F, Kump PK, Nakov R, Goldenberg SD, Satokari R, Tkatch S, Sanguinetti M, Cammarota G, Dorofeev A, Gubska O, Laniro G, Mattila E, Arasaradnam RP, Sarin SK, Sood A, Putignani L, Alric L, Baunwall SMD, Kupcinskas J, Link A, Goorhuis AG, Verspaget HW, Ponsioen C, Hold GL, Tilg H, Kassam Z, Kuijper EJ, Gasbarrini A, Mulder CJJ, Williams HRT, Vehreschild MJGTet al., 2021, A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group, UNITED EUROPEAN GASTROENTEROLOGY JOURNAL, Vol: 9, Pages: 229-247, ISSN: 2050-6406

Journal article

Ghani R, Mullish B, Innes A, Szydlo RM, Apperley JF, Olavarria E, Palanicawandar R, Kanfer E, Milojkovic D, McDonald JAK, Brannigan E, Thursz MR, Williams HRT, Davies FJ, Pavlu J, Marchesi Jet al., 2021, Faecal microbiota transplant (FMT) prior to allogeneic haematopoietic cell transplantation (HCT) in patients colonised with multidrug-resistant organisms (MDRO) results in improved survival, ECCMID

Conference paper

NICE, 2021, Faecal microbiota transplant for recurrent or refractory Clostridioides difficile infection, Medtech innovation briefing [MIB247]

Report

Akhbari P, Jaggard MK, Boulange CL, Vaghela U, Graca G, Bhattacharya R, Lindon JC, Williams HRT, Gupte CMet al., 2021, Differences between infected and noninfected synovial fluid, BONE & JOINT RESEARCH, Vol: 10, Pages: 85-95, ISSN: 2046-3758

Journal article

Gallagher K, Radhakrishnan ST, Li JV, Thurz MR, Holmes E, Williams HRTet al., 2021, DEVELOPMENT OF A TARGETED METABOLOMIC URINE-BASED PANEL FOR INFLAMMATORY BOWEL DISEASE, Publisher: BMJ PUBLISHING GROUP, Pages: A114-A114, ISSN: 0017-5749

Conference paper

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