A standardised model for stool banking for faecal microbiota transplantation : a consensus report from a multidisciplinary UEG working group

Background Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council. Objective Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document. Methods Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation. Results A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening. Conclusion The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.Peer reviewe

Contrasting patterns of population structure and gene flow facilitate exploration of connectivity in two widely distributed temperate octocorals

This is the final version of the article. Available from Springer Nature via the DOI in this record.Connectivity is an important component of metapopulation dynamics in marine systems and can influence population persistence, migration rates and conservation decisions associated with Marine Protected Areas (MPAs). In this study, we compared the genetic diversity, gene flow and population structure of two octocoral species, Eunicella verrucosa and Alcyonium digitatum, in the northeast Atlantic (ranging from the northwest of Ireland and the southern North Sea, to southern Portugal), using two panels of thirteen and eight microsatellite loci, respectively. Our results identified regional genetic structure in E. verrucosa partitioned between populations from southern Portugal, northwest Ireland, and Britain/France; subsequent hierarchical analysis of population structure also indicated reduced gene flow between southwest Britain and northwest France. However, over a similar geographical area, A. digitatum showed little evidence of population structure, suggesting high gene flow and/or a large effective population size; indeed, the only significant genetic differentiation detected in A. digitatum occurred between North Sea samples and those from the English Channel/northeast Atlantic. In both species the vast majority of gene flow originated from sample sites within regions, with populations in southwest Britain being the predominant source of contemporary exogenous genetic variants for the populations studied. Unsurprisingly, historical patterns of gene flow appeared more complex, though again southwest Britain appeared an important source of genetic variation for both species. Our findings have major conservation implications, particularly for E. verrucosa, a protected species in UK waters and listed by the IUCN as ‘Vulnerable’, and for the designation and management of European MPAs.We thank Natural England (project No. RP0286, contract No. SAE 03-02-146), the NERC (grant No. NE/L002434/1) and the University of Exeter for funding this research. Additional funding for sample collection, travel and microsatellite development was provided by the EU Framework 7 ASSEMBLE programme, agreement no. 227799, and NERC grant No. NBAF-362

A concept for biological valuation in the marine environment

In order to develop management strategies for sustainable use and conservation in the marine environment, reliable and meaningful, but integrated ecological information is needed. Biological valuation maps that compile and summarize all available biological and ecological information for a study area, and that allocate an overall biological value to subzones, can be used as baseline maps for future spatial planning at sea. This paper provides a concept for marine biological valuation which is based on a literature review of existing valuation criteria and the consensus reached by a discussion group of experts

Temporal Regulation of Immune Response during GvHD via IL-33/ST2 axis

Similar abstract has been appporved for a conference (OAK22720). IL-33 binding to the receptor suppression of tumorigenicity 2 (ST2) produces proinflammatory and anti-inflammatory effects. Increased levels of soluble ST2 (sST2) are a biomarker for steroid-refractory GVHD and mortality. However, whether sST2 has a role as an immune modulator or only as a biomarker during GVHD was unclear. We show increased IL-33 production by non-hematopoietic cells in the GI tract in mice postconditioning and patients during GVHD. Exogenous IL-33 administration during the peak inflammatory response worsened GVHD. Conversely, GVHD lethality and TNF-α production was significantly reduced in il33-/- recipients. ST2 was upregulated on murine and human alloreactive T cells and sST2 increased as experimental GVHD progressed. Concordantly, st2-/- versus wildtype donor T cells had a marked reduction in GvHD lethality and GI histopathology. Alloantigen-induced IL-18 receptor upregulation was lower in st2-/- T cells, and linked to reduced IFN-γ production by st2-/- versus wildtype T cells during GVHD. Blockade of IL-33/ST2 interactions during allo-hematopoietic cell transplantation by exogenous ST2-Fc infusions had a marked reduction in GVHD lethality indicating a role of ST2 as a decoy receptor modulating GVHD. Together, these studies point to targeting of the IL-33/ST2 axis as a novel and potent target for GVHD therapy