Secretory IgA (SIgA) is critical for maintaining the intestinal barrier. A dysregulated B-cell compartment and altered Ig secretion have been well documented in Crohn's disease (CD) patients, although their origin is unknown. To unravel the role of mucosal humoral immunity in CD pathogenesis, we in-depth phenotype colonic plasma cell (PC) differentiation in CD at the single-cell level, linked to ex vivo functional characterization and experimental mouse models with a congenital mitochondrial defect or under glucose-free high-protein dietary intervention. Here, we demonstrate that despite expanded colonic B cells, CD patients in remission present significantly diminished mucosal dimeric IgA and fecal SIgA. Colonic plasmablasts and immature CD19+CD45+ PCs are increased at the expense of the mature CD19-CD45- phenotype. Accordingly, CD-derived ex vivo differentiated PCs display impaired maturation into dimeric IgA-secreting PCs. In this study, patient-derived data from colonic RNA-seq, spatial single-cell proteomics, and plasma metabolomics are combined with data from both mouse models and highlight the crucial role of mitochondrial oxidative phosphorylation in colonic IgA+-PC differentiation, suggesting promising directions for future therapeutic strategies.

Background Clostridioides difficile (C. difficile) remains the leading cause of healthcare-associated diarrhoea, posing treatment challenges due to antibiotic resistance and high relapse rates. Fecal microbiota transplantation (FMT) is a novel treatment strategy to prevent relapses of C. difficile infection (CDI), however the exact components conferring colonisation resistance are unknown, hampering its translation to a medicinal product. Development of novel products independent of antibiotics, which increase colonisation resistance or induce protective immune mechanisms are urgently needed. Objectives To establish a framework for a Controlled Human Infection Model (CHIM) for C. difficile, in which healthy volunteers are exposed to toxigenic C. difficile spores, offering the possibility to test novel approaches and identify microbiota and immunological targets. Whereas experimental exposure to non-toxigenic C. difficile (NTCD) has been done before, a toxigenic C. difficile CHIM faces ethical, scientific, logistical and biosafety challenges. Sources Specific challenges in developing a C. difficile CHIM were discussed by a group of international experts during a workshop organized by Inno4Vac, an IHI-funded consortium. Content The experts agreed that the main challenges are: developing a clinically relevant CHIM which induces mild to moderate CDI symptoms but no severe CDI, determining optimal C. difficile inoculum dose and understanding the timing and duration of antibiotic pre-treatment in inducing susceptibility to CDI in healthy volunteers. Implications Should these challenges be tackled, a C. difficile CHIM not only provides a way forward for the testing of novel products but also offers a framework for better understanding of the pathophysiology, pathogenesis and immunology of C. difficile colonisation and infection.

ZusammenfassungDie Ösophagogastroduodenoskopie (ÖGD), die endoskopische retrograde Cholangiopankreatikografie (ERCP) sowie die Koloskopie (KOLO) bergen stets das Risiko einer Transmission von Erregern. Leider gibt es bislang nur wenige Daten zu den Ursachen und Erregerspektren für diese Ereignisse.In einer systematischen Literaturrecherche der Worldwide Outbreak Database, der PubMed und der Embase wurden entsprechende Ausbrüche hinsichtlich der Ausbruchsursache, des Erregerspektrums, der Attack Rate und Letalität sowie der daraufhin eingeleiteten Hygienemaßnahmen evaluiert.Es wurden insgesamt 73 Ausbrüche (ÖDG: 24; ERCP: 42; KOLO: 7) eingeschlossen mit Attack Rates in Höhe von 3,5%, 7,1% und 12,8%. Die zugehörigen Letalitäten betrugen 6,3%, 12,7% und 10,0%. Im Rahmen der ÖGD ereigneten sich vor allem Transmissionen von Enterobakterien mit einem großen Anteil multiresistenter Isolate. Via ERCP wurden überwiegend Nonfermenter übertragen. Die häufigste Ursache für die akzidentelle Verwendung kontaminierter Endoskope war menschliches Versagen während der Endoskopaufbereitung.Dem Anwender sollte das Risiko einer Übertragung stets bewusst sein, um diese frühestmöglich erkennen und fortan unterbinden zu können. Darüber hinaus müssen Mitarbeiter regelmäßig in der Aufbereitung von Medizinprodukten geschult werden. Die Verwendung von Einmalendoskopen senkt zwar das Übertragungsrisiko von Erregern, erhöht jedoch andererseits die Abfallmenge und ggf. auch die Kosten.

Objectives: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study. Methods: The IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. Results: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (4 4.6%) metronidazole patients and 150/ 219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33-0.65]; non-severe: HR 0.39; [95% CI, 0.24-0.60]; severe: HR 0.52; [95% CI, 0.28-0.95]). Discussion: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels. Jana Conrad, Clin Microbiol Infect 2024;30:1433

Primary sclerosing cholangitis (PSC) is an inflammatory disease of the biliary tract eventually leading to bile duct destruction, liver failure, cholangiocellular adenocarcinoma and/or death. No disease modifying treatments are available. Especially cytotoxicity of bile acids, are discussed as potential driver of disease progression. Cholangiocytes are protected by a bicarbonate umbrella formed by the glycocalyx, a dense layer of membrane bound polyglycans extending into the extracellular space. Bile of PSC patients harbors a unique microbiome. Here we identified a new factor in the pathogenesis of PSC. The bacterial degradation of sialic acid and galactose are associated with a poor event free survival of PSC patients and could identify bacterial liberation of sialic acid as crucial element in cholangiocyte damage using cell culture experiments, individualized organoid models and liver biopsies. With this study the view on bacteria-host interactions in bile duct associated diseases is widened. Functional patterns of the bacterial community are crucial for bile duct destruction in PSC patients. This opens a new field of diagnostic tools, disease modifying treatment options and identification of patients at risk. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by the Deutsche Forschungsgemeinschaft (DFG German Research Foundation) under Germany Excellence Strategy EXC 2155 RESIST Project ID 390874280 and by the German Centre for Infection Research (DZIF e.V.). This work was supported by a grant from the German Federal Ministry of Education and Research (reference number: 01EO1302) and by the Helmholtz Association Initiative on Aging and Metabolic Programming. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study had been approved by the ethics committee of the Hannover Medical School (approval no. 220- 2007, approval no. 3241- 2016, approval no. 9660\_BO\_K\_2021 and approval no. 10183\_BO\_K\_2022). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Raw data from 16S amplicon sequencing, metagenomic sequence data, bacterial genome data and data from mass spectrometry will be available upon publication after peer-review. All additional data in the present study are available upon reasonable request to the authors.

BackgroundAdenoma detection with polypectomy during total colonoscopy reduces the incidence of colorectal cancer (CRC) and colorectal cancer-associated mortality. The adenoma detection rate (ADR) is an established quality indicator, which is associated with a decreased risk for interval cancer. An increase in ADR could be demonstrated for several artificially intelligent, real-time computer-aided detection (CADe) systems in selected patients. Most studies concentrated on outpatient colonoscopies. This sector often lacks funds for applying costly innovations like CADe. Hospitals are more likely to implement CADe and information about the impact of CADe in the distinct patient cohort of hospitalized patients is scarce.MethodsIn this prospective, randomized-controlled study, we compared colonoscopies performed with or without computer-aided detection (CADe) system (GI Genius, Medtronic) performed at University Medical Center Schleswig-Holstein, Campus Luebeck. The primary endpoint was ADR.ResultsOverall, 232 patients were randomized with n = 122 patients in the CADe arm and n = 110 patients in the control arm. Median age was 66 years (interquartile range 51-77). Indication for colonoscopy was most often workup for gastrointestinal symptoms (88.4%) followed by screening, post-polypectomy and post-CRC surveillance (each 3.9%). Withdrawal time was significantly prolonged (11 vs. 10 min, p = 0.039), without clinical relevance. Complication rate was not different between the arms (0.8% vs. 4.5%; p = 0.072). The ADR was significantly increased in the CADe arm compared to the control (33.6% vs. 18.1%, p = 0.008). ADR increase was particularly strong for the detection in elderly patients aged >= 50 years (OR 6.3, 95% CI 1.7 - 23.1, p = 0.006).ConclusionThe use of CADe is safe and increases ADR in hospitalized patients.

Esophagogastroduodenoscopy (EGD), endoscopic retrograde cholangiopancreatography (ERCP) and colonoscopy (CLN) come with a potential risk of pathogen transmission. Unfortunately, up to now data on the causes and the distribution of pathogens is rather sparse.We performed a systematic review of the medical literature using the Worldwide Outbreak Database, the PubMed, and Embase. We then checked so-retrieved articles for potential sources of the outbreak, the spectrum of pathogens, the attack rates, mortality and infection control measures.In total 73 outbreaks (EGD: 24, ERCP: 42; CLN: 7) got included. The corresponding attack rates were 3.5%, 7.1% and 12.8% and mortality rates were 6.3%, 12.7% and 10.0% respectively. EGD was highly associated with transmission of enterobacteria including a large proportion of multi-drug resistant strains. ERCP led primarily to transmission of non-fermenting gram-negative rods. The most frequent cause was human failure during reprocessing regardless of the type of endoscope.Staff working in the field of endoscopy should always be aware of the possibility of pathogen transmission in order to detect and terminate those events at the early most time point. Furthermore, proper ongoing education of staff involved in the reprocessing and maintenance of endoscopes is crucial. Single-use devices may be an alternative option and lower the risk of pathogen transmission, but on the downside may also increase costs and waste.

INTRODUCTION:Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease.OBJECTIVES:To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease.METHODOLOGY:To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019.RESULTS:There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; n = 556), followed by patients with primary sclerosing cholangitis (PSC; n = 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P  < 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P  = 0.02, P  < 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P  < 0.001).CONCLUSION:Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future.

Question: A 28-year-old white man with diffuse large B-cell lymphoma developed sudden weight gain and jaundice 2 weeks after autologous stem cell transplantation. The patient complained about abdominal pain and fatigue. He had no prior history of chronic liver disease or cholecystolithiasis but had initially displayed hepatic manifestation of lymphoma. On examination, he presented with an extended abdomen, leg edema, jaundice, and signs of hepatic encephalopathy. Lab results showed beginning liver failure with abrupt rise of liver enzymes (glutamate-oxaloacetate transaminase 3617 U/L, glutamate-pyruvate transaminase 1283 U/I) and hyperbilirubinemia (bilirubin 96.7 μmol/L) as well as deranged coagulation (international normalized ratio 2.5).

A 67-year-old male patient underwent atypical hepatic resection of segments 2, 3, and 7 with hepaticojejunostomy due to Caroli disease. Two months later, the patient presented with cholestasis and cholangitis most likely due to anastomotic stricture. The patient was treated with 8.5 French (F), Yamakawa type, percutaneous transhepatic cholangiodrainage (PTCD) (PerkuBil, Pflugbeil) as the hepaticojejunostomy could not be reached via endoscopy using colonoscope, balloon, and motorized power spiral scope (Figure A). Percutaneous cholangioscopy revealed a stricture and biopsies were obtained (SpyGlass Discover, Boston Scientific). Histopathologic analysis revealed reactive polypoid granulation tissue with no evidence of malignancy. The PTCD was sequentially expanded to 18F. Two PTCD withdrawal attempts failed, resulting in recurrent cholangitis and the need for reinterventions. In total, the patient was treated with PTCD for 36 months. To improve the quality of life without repeated interventions, a custom-built, biliary, biodegradable stent (BDS) made of polydioxanone was inserted under radiological and cholangioscopic guidance (SX-ELLA, 10 mm/60 mm; 3 radiopaque markers, ELLA-CS/Leufen Medical GmbH) (Figure B–C). To avoid intervention-related cholangitis, an 8.5F PTCD (Cook Medical) was inserted through the BDS (Figure D). On the third day, cholangioscopy revealed early decomposition of the BDS. A shortened 12F Yamakawa PTCD was placed proximal of the BDS to maintain percutaneous access (Figure E). During an observation period of 4 weeks, the patient showed no clinical or laboratory signs of cholangitis. On day 28, contrast imaging by PTCD showed slender bile ducts without stricture and rapid drainage of the contrast into the jejunum (Figure F). Cholangioscopy showed a wide hepaticojejunostomy with remnants of the BDS. Video 1 shows the cholangioscopic findings before placement of the BDS and its degradation during the observation period. This case demonstrates the treatment success of a biliary BDS in a patient with PTCD-refractory stenosis. The authors thank Professor Jens U. Marquardt and Carlos Maass for their support. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI1OWVkODVlYTRhMWQxMWYxODRkMWE1ZGYwOTI5NTM1NiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzAyNzAyMTQ5fQ.Kx9kwVlAJ4XmZuugYFyKxjO53tGkelZ9KU4n4aelLYi8uI04Eo7CqsFvEqFJWMEVz5RGGOfzcswB4keex23LwCP70ZiCTr2WvsY0rqBd4zJ6s82vtVPgg-ZQgfAd0xnGMTY-hS52mky_3UOCIk_xxOzeT5fTkdIidEmn8yGzSNXqISjTNrmbQwAvds_UehMzKxKBG9pENQMEyQjRSx3GLO3KOhP70J2Zq8SQSUXAieSTDhlBUd17BuXZvi-iehSmlYUkNMALvn9z1FktOQTCRUXKhvSlfcqpKoJZyLIGac_prwkzpXI6HZ7PtCvGxe9c3hEE-dffiaT6Gz8VJHWQZw Download .mp4 (15.18 MB) Help with .mp4 files Video 1Cholangioscopy showing the stricture prior intervention and the placement of the BDS at day 0, as well as the findings on day 3 and day 28.

Zusammenfassung Einführung Der Fäkale Mikrobiota-Transfer (FMT) ist eine Behandlung zur Modulation der gastrointestinalen Mikrobiota. Der Einsatz bei rezidivierender Clostridioides-difficile-Infektion (rCDI) ist europaweit etabliert und wird in nationalen und internationalen Leitlinien empfohlen. Der FMT ist in Deutschland im Fallpauschalensystem der Krankenhäuser kodierfähig. Eine auf dieser Kodierung basierende umfassende Erhebung zur Häufigkeit des Einsatzes fehlt bislang. Material und Methodik Berichte des Instituts für das Entgeltsystem im Krankenhaus (InEK), des Statistischen Bundesamtes (DESTATIS) und Qualitätsberichte der Krankenhäuser 2015–2021 wurden auf FMT-Kodierung hin untersucht und im Rahmen einer strukturierten Expertenkonsultation bewertet. Ergebnisse Zwischen 2015 und 2021 wurden von 175 Krankenhäusern 1.645 FMT-Verfahren kodiert. Von 2016 bis 2018 waren dies jährlich im Median 293 (274–313) FMT, gefolgt von einem konstanten Rückgang in den folgenden Jahren auf 119 FMT im Jahr 2021. Patienten/-innen mit FMT waren zu 57,7% weiblich, im Median 74 Jahre alt und der FMT wurde zu 72,2% koloskopisch appliziert. Bei 86,8 % der Fälle wurde eine CDI als Hauptdiagnose genannt, gefolgt von 7,6% eine Colitis ulcerosa. Diskussion In Deutschland wird der FMT seltener eingesetzt als im europäischen Vergleich. Eine Anwendungshürde ist die behördliche Einordnung des FMT als nicht zugelassenes Arzneimittel, die zu erheblich höherem Aufwand bei Herstellung und Verabreichung führt und eine Erstattung erschwert. Die Europäische Kommission hat kürzlich eine Verordnung vorgeschlagen, den FMT als Transplantation einzuordnen. Dies könnte die regulatorische Situation des FMT in Deutschland perspektivisch verändern und so zu einem flächendeckenden Angebot eines in Leitlinien empfohlenen Therapieverfahrens beitragen.

Introduction Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far.Material and methodology Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation.Results Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%.Discussion In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.

Background Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease. Methods Serum samples were obtained from 55 patients with Crohn’s disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale. Results Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2. Conclusions Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.

Background and aims:Bacterial cholangitis is a common complication in patients with ischemic type biliary lesions and/or anastomotic strictures after liver transplantation (LTX). Patients frequently need antibiotics and endoscopic retrograde cholangiography (ERC) to improve the bile flow. Antibiotic treatment is based on findings in standard microbiological cultivation (SMC) of bile. However, the cultivation techniques are limited to a subset of bacteria easy-to-cultivate. Therefore, the aim of our study was to evaluate the value of next generation sequencing as an additional diagnostic tool to SMC in ischemic type biliary lesions and/or anastomotic strictures. Methods:We sequenced the V1-V2 region of the 16S rRNA gene in 242 stored bile samples in patients after LTX and compared the results with findings of SMC. SMC was performed in n = 135 (56%) fresh bile samples in addition to NGS. SMC was part of the clinical routine in these patients. Results:NGS detected bacterial genera in bile samples more often than SMC (P = 5.42 × 10-74). SMC showed insufficient discovery of bacterial genera compared to NGS with better performance in patients receiving antibiotics prior to ERC. SMC missed many bacterial genera detected by NGS. Conclusions:NGS was more sensitive in detecting bacteria in bile than SMC, no clinical parameters could be used to improve discovery rates in SMC and many genera were missed by SMC. Therefore, NGS should be used in a combined approach with SMC for improved diagnostics to achieve more specific and targeted antibiotic treatments.

This study aims to characterize the biliary microbiome as neglected factor in patients with ischaemic-type biliary lesions (ITBL) after liver transplantation. Therefore, the V1-V2 region of the 16S rRNA gene was sequenced in 175 bile samples. Samples from patients with anastomotic strictures (AS) served as controls. Multivariate analysis and in silico metagenomics were applied cross-sectionally and longitudinally. The microbial community differed significantly between ITBL and AS in terms of alpha and beta diversity. Both, antibiotic treatment and stenting were associated independently with differences in the microbial community structure. In contrast to AS, in ITBL stenting was associated with pronounced differences in the biliary microbiome, whereas no differences associated with antibiotic treatment could be observed in ITBL contrasting the pronounced differences found in AS. Bacterial pathways involved in the production of antibacterial metabolites were increased in ITBL with antibiotic treatment. After liver transplantation, the biliary tract harbours a complex microbial community with significant differences between ITBL and AS. Fundamental changes in the microbial community in ITBL can be achieved with biliary stenting. However, the effect of antibiotic treatment in ITBL was minimal. Therefore, antibiotics should be administered wisely in order to reduce emerging resistance of the biliary microbiome towards external antibiotics.

A 75-year-old male patient was admitted to the emergency department with febrile temperature. The patient presented with multiple, very dark nevi all over his face and body, previously diagnosed as benign.

We describe the case of a 40-year-old patient with active Crohn’s Disease (CD)-who developed neurological symptoms and was subsequently diagnosed with cerebral demyelination shortly after re-exposure to a therapy with Adalimumab. Based on the current state of scientific knowledge, we here discuss whether concurrent diagnosis of demyelinating disease and the anti-tumor-necrosis-factor (TNF)-alpha-therapy develop independently or whether direct causality is more likely. Basis for this purpose are the diseases´ incidence rates and the different pathophysiological hypotheses for demyelination under anti-TNF-alpha-therapy. Due to high incidence of cerebral demyelination and lack of laboratory or clinical markers to differentiate the underlying influences, a definite conclusion cannot be drawn. Based on the presented findings and state of the literature, we finally deduce recommendations for clinical practice and research gaps.

Background: Fecal microbiota transfer (FMT) has become a standard of care in the prevention of multiple recurrent Clostridioides difficile (rCDI) infection. Aim: While primary cure rates range from 70-80% following a single treatment using monodirectional approaches, cure rates of combination treatment remain largely unknown. Methods: In a retrospective case-control study, outcomes following simultaneous bidirectional FMT (bFMT) with combined endoscopic application into the upper and lower gastrointestinal tract, compared to standard routes of application (endoscopy via upper or lower gastrointestinal tract and oral capsules; abbreviated UGIT, LGIT and CAP) on day 30 and 90 after FMT were assessed. Statistical matching partners were identified using number of recurrences ( < 3; >= 3), age and gender. Results: Primary cure rates at D30 and D90 for bFMT were 100% ( p = .001). The matched control groups showed cure rates of 81.3% for LGIT ( p = .010), 62.5% for UGIT ( p = .0 0 0) and 78.1% for CAP ( p = .005) on D30 and 81.3% for LGIT ( p = .010), 59.4% for UGIT ( p = .0 0 0) and 71.9% for CAP ( p = .001) on D90. Conclusion: In our analysis, bFMT on the same day significantly increased primary cure rate at D30 and D90. These data require prospective confirmation but suggest that route of application may play a signif-icant role in optimizing patient outcomes. ClinicalTrials.gov no: NCT026 8106 8 (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Background. Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on colonization with C. difficile are largely unavailable. Methods. C. difficile status was assessed by GDH EIA and real-time PCR targeting the toxin A (tcdA) and B (tcdB) genes. 16S V3 and V4 gene sequencing results from fecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta diversity, LefSe, and the Piphillin functional inference approach to estimate functional capacity. Results. 1506 patients were recruited into a prospective observational study (DRKS00005335) upon admission into one of five academic hospitals. 936 of them provided fecal samples on admission and at discharge and were thus available for longitudinal analysis. Upon hospital admission, 5.5% (83/1506) and 3.7% (56/1506) of patients were colonized with toxigenic (TCD) and nontoxigenic C. difficile (NTCD), respectively. During hospitalization, 1.7% (16/936) acquired TCD. Risk factors for acquisition of TCD included pre-existing lung diseases, lower GI endoscopy and antibiotics. Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococcus spp. Metagenomic pathway analysis identified steroid biosynthesis as the most underrepresented metabolic pathway in patients who later acquire C. difficile colonization. Conclusions. Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition.