Browsing by Subject "ACTIVE ULCERATIVE-COLITIS"

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  • Holster, Savanne; Hooiveld, Guido J.; Repsilber, Dirk; de Vos, Willem M.; Brummer, Robert J.; König, Julia (2019)
    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.
  • Koulaouzidis, Anastasios; Sipponen, Taina; Nemeth, Artur; Makins, Richard; Kopylov, Uri; Nadler, Moshe; Giannakou, Andry; Yung, Diana E.; Johansson, Gabriele Wurm; Bartzis, Leonidas; Thorlacius, Henrik; Seidman, Ernest G.; Eliakim, Rami; Plevris, John N.; Toth, Ervin (2016)
    Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images. Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels. Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months. Overall, correlation between FC and LS was weak (r (s): 0.232, P <0.001). When two clinically significant FC thresholds (100 and 250 mu g/g) were examined, the r (s) between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS a parts per thousand yen 135) or negative (LS <135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 mu g/g with sensitivity 0.59 and specificity 0.41. Limitations: Retrospective design. LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level a parts per thousand yen 76 mu g/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.
  • Koenig, J.; Siebenhaar, A.; Hoegenauer, C.; Arkkila, P.; Nieuwdorp, M.; Noren, T.; Ponsioen, C. Y.; Rosien, U.; Rossen, N. G.; Satokari, R.; Stallmach, A.; de Vos, W.; Keller, J.; Brummer, R. J. (2017)
    Background Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. Aim To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. Methods Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. Results Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. Conclusions Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
  • Holster, S.; Repsilber, D.; Geng, D.; Hyotylainen, T.; Salonen, A.; Lindqvist, C. M.; Rajan, S. K.; de Vos, W. M.; Brummer, R. J.; König, J. (2021)
    Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
  • Cammarota, Giovanni; Ianiro, Gianluca; Tilg, Herbert; Rajilic-Stojanovic, Mirjana; Kump, Patrizia; Satokari, Reetta; Sokol, Harry; Arkkila, Perttu; Pintus, Cristina; Hart, Ailsa; Segal, Jonathan; Aloi, Marina; Masucci, Luca; Molinaro, Antonio; Scaldaferri, Franco; Gasbarrini, Giovanni; Lopez-Sanroman, Antonio; Link, Alexander; De Groot, Pieter; de Vos, Willem M.; Hoegenauer, Christoph; Malfertheiner, Peter; Mattila, Eero; Milosavljevic, Tomica; Nieuwdorp, Max; Sanguinetti, Maurizio; Simren, Magnus; Gasbarrini, Antonio; European FMT Working Grp (2017)
    Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
  • Lahtinen, Perttu; Mattila, Eero; Anttila, Veli-Jukka; Tillonen, Jyrki; Teittinen, Matti; Nevalainen, Pasi; Salminen, Seppo; Satokari, Reetta; Arkkila, Perttu (2017)
    Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli (E. coli) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.
  • Cammarota, Giovanni; Ianiro, Gianluca; Kelly, Colleen R.; Mullish, Benjamin H.; Allegretti, Jessica R.; Kassam, Zain; Putignani, Lorenza; Fischer, Monika; Keller, Josbert J.; Costello, Samuel Paul; Sokol, Harry; Kump, Patrizia; Satokari, Reetta; Kahn, Stacy A.; Kao, Dina; Arkkila, Perttu; Kuijper, Ed J.; Vehreschild, Maria J. G. T.; Pintus, Cristina; Lopetuso, Loris; Masucci, Luca; Scaldaferri, Franco; Terveer, E. M.; Nieuwdorp, Max; Lopez-Sanroman, Antonio; Kupcinskas, Juozas; Hart, Ailsa; Tilg, Herbert; Gasbarrini, Antonio (2019)
    Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres. Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice, Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.
  • Lahtinen, Perttu; Jalanka, Jonna; Hartikainen, Anna; Mattila, Eero; Hillilä, Markku; Punkkinen, Jari; Koskenpato, Jari; Anttila, Veli-Jukka; Tillonen, Jyrki; Satokari, Reetta; Arkkila, Perttu (2020)
    Summary Background Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis. Aim To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS. Methods Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight. Results The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms. Conclusions FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.
  • Holster, Savanne; Lindqvist, Carl Mårten; Repsilber, Dirk; Salonen, Anne; de Vos, Willem M.; König, Julia; Brummer, Robert J. (2019)
    OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota. METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing. RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P=0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P <0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group. CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.