Publications
180 results found
Wang Y, Abu-Sbeih H, Tang T, et al., 2022, Endoscopic Severity Score of Immune-Mediated Colitis Is More Effective in Guiding Medical Treatment Than Clinical Severity Grade, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S503-S504, ISSN: 0002-9270
Schreiber S, Powell N, Rieder F, et al., 2022, Efficacy of Deucravacitinib, an Oral, Selective, TYK2 Inhibitor, in Patients With Moderately to Severely Active Ulcerative Colitis and Prior Exposure to Biologic Therapy: Subanalysis From the Phase 2 LATTICE-UC Study, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S632-S633, ISSN: 0002-9270
Pavlidis P, Tsakmaki A, Treveil A, et al., 2022, Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease, Cell Reports, Vol: 40, Pages: 1-19, ISSN: 2211-1247
Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different cytokines responsible for mediating canonical mucosal immune responses. By profiling the transcriptome of human colonic organoids treated with the canonical cytokines interferon gamma, interleukin-13, -17A, and tumor necrosis factor alpha with next-generation sequencing, we unveil shared and distinct regulation patterns of epithelial function by different cytokines. An integrative analysis of cytokine responses in diseased tissue from patients with IBD (n = 1,009) reveals a molecular classification of mucosal inflammation defined by gradients of cytokine-responsive transcriptional signatures. Our systems biology approach detected signaling bottlenecks in cytokine-responsive networks and highlighted their translational potential as theragnostic targets in intestinal inflammation.
Alexander J, Powell N, Ibraheim H, et al., 2022, Oral Beclomethasone Dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis, Journal for ImmunoTherapy of Cancer, Vol: 10, Pages: 1-10, ISSN: 2051-1426
IntroductionSystemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically-acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesised that BD would be an effective treatment for CPI-induced colitis.MethodsWe performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centres between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment.ResultsTwenty-two patients (fourteen male) with a median age of 64 (range 45-84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (CTCAE grade diarrhoea = 2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo endoscopic score [MES] = 2) in two patients (9%), mild inflammation (MES = 1) in nine patients (41%) and normal findings (MES = 0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhoea = 0). 10 patients (45%) had symptomatic relapse on cessation of BD, half within seven days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD.ConclusionsTopical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflamma
Alexander J, Kennedy NA, Lees CW, et al., 2022, SARS-CoV-2 vaccination for patients with inflammatory bowel disease – Authors' reply, The Lancet Gastroenterology and Hepatology, Vol: 6, Pages: 523-524, ISSN: 2468-1253
Constable L, Iqbal N, Cozzetto D, et al., 2022, IL22 PRODUCING INKT AND CD4+T-CELLS DRIVE DYSREGULATION OF THE EXTRACELLULAR MATRIX IN PERIANAL FISTULAS, Publisher: BMJ PUBLISHING GROUP, Pages: A23-A23, ISSN: 0017-5749
Lo J, Cozzetto D, Stolarczyk E, et al., 2022, NKP46+TRAIL-CD49B+GROUP 1 INNATE LYMPHOID CELLS MEDIATE HEPATITIS IN AN INTERFERON-γ DEPENDENT MANNER, Publisher: BMJ PUBLISHING GROUP, Pages: A80-A80, ISSN: 0017-5749
Lo J, Cozzetto D, Liu Z, et al., 2022, IMMUNE CHECKPOINT INHIBITOR-INDUCED COLITIS IS MEDIATED BY CXCR6+POLYFUNCTIONAL LYMPHOCYTES AND DEPENDENT ON IL23/IFNG AXIS, Publisher: BMJ PUBLISHING GROUP, Pages: A56-A56, ISSN: 0017-5749
Liu Z, Lo J, Alexander J, et al., 2022, DYSREGULATED GUT MICROBIOTA-HOST METABOLISM UNDERPINS IMMUNE ACTIVATION IN A MICROBIOTA-DEPENDENT MODEL OF ULCERATIVE COLITIS, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A19-A20, ISSN: 0017-5749
Alexander J, Mullish B, Danckert N, et al., 2022, COVID-19 VACCINATION RESPONSE IN IMMUNOSUPPRESSED PATIENTS WITH IBD IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, Publisher: BMJ PUBLISHING GROUP, Pages: A36-A36, ISSN: 0017-5749
Lees CW, Ahmad T, Lamb CA, et al., 2022, Withdrawal of the British Society of Gastroenterology IBD risk grid for COVID-19 severity, GUT, ISSN: 0017-5749
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, 2022, Su1485: COVID-19 VACCINE-INDUCED ANTIBODY RESPONSES ARE IMPAIRED IN IBD PATIENTS TREATED WITH INFLIXIMAB, USTEKINUMAB OR TOFACITINIB, BUT NOT THIOPURINES OR VEDOLIZUMAB, Gastroenterology, Vol: 162, ISSN: 0016-5085
, 2022, Su1611: POOR RESPONSE TO ANTI-SARS-COV-2 VACCINATION IN IMMUNOSUPPRESSED INFLAMMATORY BOWEL DISEASE PATIENTS IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, Gastroenterology, Vol: 162, ISSN: 0016-5085
Alexander JL, Kennedy NA, Ibraheim H, et 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·
Lamb CA, Saifuddin A, Powell N, et al., 2022, The Future of Precision Medicine to Predict Outcomes and Control Tissue Remodeling in Inflammatory Bowel Disease, GASTROENTEROLOGY, Vol: 162, Pages: 1525-1542, ISSN: 0016-5085
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- Citations: 15
Pavlidis P, Joshi D, El Sherif Y, et al., 2022, Faecal calprotectin is a surrogate marker of biliary inflammation in primary sclerosing cholangitis associated inflammatory bowel disease, FRONTLINE GASTROENTEROLOGY, ISSN: 2041-4137
Lin S, Kennedy NA, Saifuddin A, et al., 2022, Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab, Nature Communications, Vol: 13, ISSN: 2041-1723
Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 – 27.5] vs 47.6 days [45.5 – 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 – 36.8] vs 58.0 days [55.0 – 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.
Chanchlani N, Lin S, Chee D, et al., 2022, Adalimumab and infliximab impair SARS-CoV-2 antibody responses: results from a therapeutic drug monitoring study in 11422 biologic-treated patients., Journal of Crohns & Colitis, Vol: 16, Pages: 389-397, ISSN: 1873-9946
BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-TNF level influences serological responses, remains unknown. METHODS: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11422 (53.3% (6084) male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between 29 th January and 30 th September 2020. Data were linked to nationally-held SARS-CoV-2 PCR results to 4 th May 2021. RESULTS: Rates of PCR confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% (178/5893), adalimumab: 3.0% (152/5074), vedolizumab: 6.7% (25/375), p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index (COI) (1.94 - 9.96) vs 5.02 (2.18 - 18.70), p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI (4.39 - 68.10, p< 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels (<0.8 mg/L) were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were anti-TNF treated. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% (12/152) patients after a median time of 183.5 days (129.8 - 235.3), without differences between drugs. CONCLUSION: Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels supports a causal relationship, although confounding factors, such as combination therapy with immunomodulator, may have
Lo JW, de Mucha MV, Henderson S, et al., 2022, A population of naive-like CD4(+) T cells stably polarized to the T(H)1 lineage, European Journal of Immunology, Vol: 52, Pages: 566-581, ISSN: 0014-2980
T-bet is the lineage-specifying transcription factor for CD4+ TH1 cells. T-bet has also been found in other CD4+ T cell subsets, including TH17 cells and Treg, where it modulates their functional characteristics. However, we lack information on when and where T-bet is expressed during T cell differentiation and how this impacts T cell differentiation and function. To address this, we traced the ontogeny of T-bet-expressing cells using a fluorescent fate-mapping mouse line. We demonstrate that T-bet is expressed in a subset of CD4+ T cells that have naïve cell surface markers and transcriptional profile and that this novel cell population is phenotypically and functionally distinct from previously described populations of naïve and memory CD4+ T cells. Naïve-like T-bet-experienced cells are polarized to the TH1 lineage, predisposed to produce IFN-γ upon cell activation, and resist repolarization to other lineages in vitro and in vivo. These results demonstrate that lineage-specifying factors can polarize T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T-helper response.
Thomas JP, Modos D, Rushbrook SM, et al., 2022, The emerging role of bile acids in the pathogenesis of inflammatory bowel disease, Frontiers in Immunology, Vol: 13, ISSN: 1664-3224
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that arises due to complex interactions between host genetic risk factors, environmental factors, and a dysbiotic gut microbiota. Although metagenomic approaches have attempted to characterise the dysbiosis occurring in IBD, the precise mechanistic pathways interlinking the gut microbiota and the intestinal mucosa are still yet to be unravelled. To deconvolute these complex interactions, a more reductionist approach involving microbial metabolites has been suggested. Bile acids have emerged as a key class of microbiota-associated metabolites that are perturbed in IBD patients. In recent years, metabolomics studies have revealed a consistent defect in bile acid metabolism with an increase in primary bile acids and a reduction in secondary bile acids in IBD patients. This review explores the evolving evidence that specific bile acid metabolites interact with intestinal epithelial and immune cells to contribute to the inflammatory milieu seen in IBD. Furthermore, we summarise evidence linking bile acids with intracellular pathways that are known to be relevant in IBD including autophagy, apoptosis, and the inflammasome pathway. Finally, we discuss how novel experimental and bioinformatics approaches could further advance our understanding of the role of bile acids and inform novel therapeutic strategies in IBD.
Lo J, Cozzetto D, Madgwick M, et al., 2022, Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on the IL23/IFNg axis, Publisher: Research Square
Immune checkpoint inhibitors (CPIs) have revolutionised cancer treatment, with previously untreatable disease now amenable to potential cure. Combination regimens of anti-CTLA-4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. CPI-induced colitis is a common and serious complication. To probe the impact of immune checkpoints on intestinal homeostasis, mice were challenged with combination anti-CTLA-4/anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. Colonic immune responses were profiled using bulk and single-cell RNA-sequencing and flow cytometry. CPI-colitis was dependent on the composition of the intestinal microbiota and was characterized by remodelling of mucosal lymphocytes with induction of polyfunctional lymphocyte responses characterized by increased expression of interferon-γ (IFNγ), other pro-inflammatory cytokines/chemokines (Il22, Il17a Ccl3, Ccl4 and Ccl9), cytotoxicity molecules (Gzmb, Gzma, Prf1, Nkg7) and the chemokine receptor Cxcr6. In comparison with mucosal lymphocytes in the steady state, polyfunctional lymphocytes from both CD4+ and CD8+ lineages upregulated costimulatory molecules and checkpoint molecules in CPI-colitis, indicating that these cells are tightly regulated. CPI-colitis was attenuated following depletion of effector lymphocytes or following blockade of the IL23/IFNγ axis. This study provides new mechanistic insights into CPI-colitis, identifying polyfunctional, cytotoxic lymphocytes as key mediators of disease. Therapeutic targeting of their effector response or regulatory networks, including the IL23/IFNγ axis likely holds the key to preventing and reversing CPI-colitis.
Iqbal N, Constable L, Tozer P, et al., 2022, Can Mesenchymal Stem Cell (MSC) apoptosis be used as a biomarker for treatment success in perianal fistulising Crohn's Disease (pCD)? Findings from a prospective pilot study, Publisher: OXFORD UNIV PRESS, Pages: I353-I353, ISSN: 1873-9946
Liu Z, Lo J, Alexander J, et al., 2022, Unravelling the microbial-derived metabolic alterations in a T-bet-/- x RAG2-/- mouse colitis model, Publisher: OXFORD UNIV PRESS, Pages: I168-I168, ISSN: 1873-9946
Steere B, Powell N, Higgs R, et al., 2022, Mirikizumab-induced upregulation of colonic transcripts correlates with improvements in stool frequency in a phase 2 study of patients with moderately to severely active Ulcerative Colitis, Publisher: OXFORD UNIV PRESS, Pages: I129-I129, ISSN: 1873-9946
Alexander J, Kennedy N, Ibraheim H, et al., 2022, COVID-19 vaccine-induced antibody responses are impaired in Inflammatory Bowel Disease patients treated with infliximab, ustekinumab or tofacitinib, but not thiopurines or vedolizumab, Publisher: OXFORD UNIV PRESS, Pages: I022-I023, ISSN: 1873-9946
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Lin S, Kennedy NA, Saifuddin A, et al., 2022, Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients, Publisher: OXFORD UNIV PRESS, Pages: I023-I025, ISSN: 1873-9946
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Lin S, Kennedy NA, Saifuddin A, et al., 2022, OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients, Journal of Crohn's & colitis, Vol: 16, Pages: i023-i025, ISSN: 1873-9946
Abstract <h4>Background</h4> Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody. Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination. <h4>Methods</h4> Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine. <h4>Results</h4> Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 – 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2). There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumab-treated patients after one or two doses of either vaccine. Antibody half-life was shorter in infliximab- than vedolizumab-treated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 – 4.1] vs 7.2 weeks [95% CI 6.8 – 7.6]) and ChAdOx1 nCoV-19 (5.3 weeks [95% CI 5.1 – 5.5] vs 9.3 weeks
Alexander J, Kennedy N, Ibraheim H, et al., 2022, OP21 COVID-19 vaccine-induced antibody responses are impaired in Inflammatory Bowel Disease patients treated with infliximab, ustekinumab or tofacitinib, but not thiopurines or vedolizumab, Journal of Crohn's & colitis, Vol: 16, Pages: i022-i023, ISSN: 1873-9946
Abstract <h4>Background</h4> Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. <h4>Methods</h4> We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) Ab assay, 53–92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15U/mL, which correlated with 20% viral neutralization). <h4>Results</h4> Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07–0.14], p<0.0001), tofa (0.36 [95% CI 0.19–0.69],p=0.002) and uste (0.56 [95% CI 0.31–1.00],p=0.049), but not with thiopurine (0.77 [95% CI
Radhakrishnan ST, Alexander JL, Mullish BH, et 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.
Iqbal N, Constable L, Tozer P, et al., 2022, Can Mesenchymal Stem Cell (MSC) apoptosis be used as a biomarker for treatment success in perianal fistulising Crohn's Disease (pCD)? Findings from a prospective pilot study, Publisher: OXFORD UNIV PRESS, Pages: I353-I353, ISSN: 1873-9946
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