The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BACKGROUND: Faecal 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. METHODS: We 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. FINDINGS: In 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. INTERPRETATION: FMT 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. FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment.

Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes in the human gut microbiome are often investigated in cohorts with preexisting health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologs did not significantly change, antibiotic-specific gene homologs with presumed resistance toward the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed an expansion of antibiotic-specific resistance gene homologs even 3 months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.Abbreviation: ARG - Antibiotic resistance gene homolog; AsRG - Antibiotic-specific resistance gene homolog; AZY - Azithromycin; CFX - Cefuroxime; CIP - Ciprofloxacin; DOX - Doxycycline; FDR - False discovery rate; GRiD - Growth rate index value; HGT - Horizontal gene transfer; NMDS - Non-metric multidimensional scaling; qPCR - Quantitative polymerase chain reaction; RPM - Reads per million mapped reads; TA - Transcriptional activity; TE - Transposable element; TPM - Transcripts per million mapped reads.

Establishing a donor stool bank for faecal microbiota transplantation: methods and feasibility.

Faecal microbiota transplantation (FMT) is a promising treatment, but donor selection and implementation in clinical practice are difficult. Here, we describe the establishment of a donor stool bank based on the Tissue Act. Stool donors were recruited among blood donors and asked to donate five times in a month. A screening questionnaire, a medical interview and testing of blood and stool were conducted before and after donations. Donations were made at home and transported to the lab, where 50 g of stool was suspended and filtered in saline and 20-mL glycerol (final concentration of 10%) to a volume of 170 mL. The processed stool was assigned a batch number, frozen within 2 h after defecation and stored at - 80 °C for up to 1 year. All steps were documented and cross-checked before donor stool were released for clinical use. Thirteen donors were eligible at the first interview and started donations. Two donors were excluded due to a positive Helicobacter pylori test, two withdrew consent and one was lost to follow-up. One donor took a single dose of NSAIDs 2 days prior to a donation, which was discarded. There were no other excluding findings at the second interview or testing. Eight of the 13 donors were approved as stool donors. All donated five times with each donation yielding 1-6 portions. Eighty-four portions were released for clinical use. Recruiting stool donors among blood donors is safe and effective. The Tissue Act yields an appropriate regulative framework for FMT.

Mining, analyzing, and integrating viral signals from metagenomic data.

BACKGROUND: Viruses are important components of microbial communities modulating community structure and function; however, only a couple of tools are currently available for phage identification and analysis from metagenomic sequencing data. Here we employed the random forest algorithm to develop VirMiner, a web-based phage contig prediction tool especially sensitive for high-abundances phage contigs, trained and validated by paired metagenomic and phagenomic sequencing data from the human gut flora. RESULTS: VirMiner achieved 41.06% ± 17.51% sensitivity and 81.91% ± 4.04% specificity in the prediction of phage contigs. In particular, for the high-abundance phage contigs, VirMiner outperformed other tools (VirFinder and VirSorter) with much higher sensitivity (65.23% ± 16.94%) than VirFinder (34.63% ± 17.96%) and VirSorter (18.75% ± 15.23%) at almost the same specificity. Moreover, VirMiner provides the most comprehensive phage analysis pipeline which is comprised of metagenomic raw reads processing, functional annotation, phage contig identification, and phage-host relationship prediction (CRISPR-spacer recognition) and supports two-group comparison when the input (metagenomic sequence data) includes different conditions (e.g., case and control). Application of VirMiner to an independent cohort of human gut metagenomes obtained from individuals treated with antibiotics revealed that 122 KEGG orthology and 118 Pfam groups had significantly differential abundance in the pre-treatment samples compared to samples at the end of antibiotic administration, including clustered regularly interspaced short palindromic repeats (CRISPR), multidrug resistance, and protein transport. The VirMiner webserver is available at http://sbb.hku.hk/VirMiner/ . CONCLUSIONS: We developed a comprehensive tool for phage prediction and analysis for metagenomic samples. Compared to VirSorter and VirFinder-the most widely used tools-VirMiner is able to capture more high-abundance phage contigs which could play key roles in infecting bacteria and modulating microbial community dynamics. TRIAL REGISTRATION: The European Union Clinical Trials Register, EudraCT Number: 2013-003378-28 . Registered on 9 April 2014.

[Faecal microbiota transplantation for the treatment of bowel disease].

Faecal microbiota transplantation (FMT) is the transferral of faeces from a healthy donor to a patient with a disease linked to disturbances in the gut microbiota. The treatment has been implemented at several hospitals in Denmark, and banks with frozen donor stool material have been established. The effect of FMT for recurrent Clostridium difficile infection is well-documented. FMT cannot be recommended for routine clinical use for inflammatory bowel disease and irritable bowel syndrome because of lack of data from clinical trials.

[Autoimmune pancreatitis is a differential diagnosis to pancreatic cancer].

Autoimmune pancreatitis is a rare benign inflammatory disease, treated with steroids. It consists of two clinical and histological distinct types, type 1 and type 2. Type 1 is part of an IgG4-related multiorgan disease, while type 2 is pancreas-specific. We here present a case of each type illustrating the difficult diagnostic process and how it can be misinterpreted as pancreatic carcinoma or cholangiocarcinoma. Though autoimmune pancreatitis is rare it should be considered as a differential diagnosis to pancreatic cancer.