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International audience; Fecal microbiota transplantation (FMT) or donor feces infusion is a therapy that aims to restore a perturbed gut microbiota composition and function. FMT is effective for treatment of patients with (multiple) recurrent Clostridioides difficile infections1–3 and recommended by current guidelines.4–6 In the near future, FMT may also become an accepted treatment option for other intestinal or extra-intestinal diseases.7FMT is performed using suspensions made of donor stool from carefully selected and screened healthy individuals.1,7 Donor screening is time consuming and costly. Before the establishment of stool banks, physicians and patients had to find their own donors. This resulted in uncontrolled application of FMT, and the logistical challenge made physicians reluctant to offer FMT to their patients. To overcome these problems, stool banks have been established.8,9 The mission of those stool banks is :to produce ready-to-use donor feces suspensions for treatment of patients,to improve the quality and safety of FMT by centralization and standardization,to increase the cost effectiveness of FMT, andto facilitate research.Stool banks are built in concordance with the model of blood banks and should follow quality standards applied to other transplantation products. Most stool banks are non-profit institutions, operating at a local (institution-based), national or international level. Recently, a UEG-funded working group was initiated to define quality standards for stool banking and FMT, which will result in further standardization of this new treatment approach. The current costs to deliver a ready-to-use stool suspension are €1050–1700 in Europe.9,10 There are also commercial initiatives,11 which may aim for much higher prices.Driven by the needs of patients, stool banks have emerged as new entities in a landscape without existing regulatory boundaries. This lack of guidance and National or European legislation may become a serious threat to providing the treatment for severely ill patients. This is also illustrated by the recent safety alert in the US about the transmission of multi-drug resistant organisms through FMT,12 which underlines the need for standardization, quality assurance, and a regulatory framework supporting the activities of stool banks. Legislation requires classification of stool as a product to treat patients. We strongly believe that stool should be considered a transplant product, or be regarded equivalent in status to blood products used for transplantation or transfusion purposes. The EU Tissue and Cells Directive (2004/23/EC) is best suited to guide FMT. Currently, this Directive does not cover FMT because the mechanism of action is not mediated by human cells. An adjustment to align this directive with the new reality of fecal transplantation is thus urgently needed. Only in the case of modification to the donated feces, other than those necessary for the conservation of the microbial community, does the product made of the donated feces become comparable to a drug and is best covered within the European directive for medicinal products intended for human use (2001/83/EC).Unfortunately, the misclassification of donor feces suspensions as a drug or pharmaceutical product, although difficult to imagine, is still one of the possible outcomes of the current discussion about classification. Currently, stool has already been classified as a drug in countries such as France, Germany, and the United Kingdom. Recently, companies have formed the “Pharmabiotic Research Institute” in Europe and the “Microbiome Therapeutics Innovation Group (MTIG)” in the US. The mission of those groups is “to improve market access,” and to “enhance the regulatory, investment, and commercial environment for microbiome therapeutic drug product development.” Both groups have published statements about the classification of FMT as a drug.13,14 MTIG actively collaborates with the Food and Drug Administration for the evaluation of safety parameters related to microbiota-based therapeutic products. Concern has been raised by the MTIG that the existence and accessibility of material from stool banks limits enrollment into clinical trials for microbiome therapeutics. This illustrates how companies are active to influence the current discussion about classification and regulation of FMT. In fact, this discussion has already been troubled by commercial interest in the US some years ago.15In this regard, it is important to mention the overall major disadvantages of classification as a drug, which will result in time-consuming and costly registration processes, and a sharp and unjustified rise in costs. Most importantly, this will negatively impact availability and innovation, obstructing, for example, the future development of single-donor individualized solutions due to the requirements for standardization of active substances. We postulate that stool treatment defined as drug treatment is counterproductive. Stool is not a standardized product that is produced in a factory, but a highly diverse and donor-specific substance of human origin (SoHO) delivered by healthy, usually unpaid, volunteer donors. Therefore, stool suspensions require suitable guidance of quality and safety measures comparable to guidance of other SoHO (blood, tissues, cells and organs) within the EU.If government authorities seek affordable and quality-assured FMT, a supportive regulatory framework, in combination with appropriate funding or reimbursement, is required for stool banks. This will not only guarantee broad access and safety of FMT, but also enable the future innovation of this new treatment strategy targeting the gut microbiota. If eventually future research results in the replacement of FMT by standardized mixtures of bacteria (or another yet undiscovered stool extract that could theoretically underly the clinical effects of FMT), these should indeed be regulated as a drug or pharmaceutical product.

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

Objectives To predict the occurrence of inactive disease in JIA in the first 2 years of disease. Methods An inception cohort of 152 treatment-naïve JIA patients with disease duration

Introduction: Wines have been traditionally produced by natural fermentations caused by the development of yeasts and lactic acid bacteria originating from the grapes and winery equipment, hence the wine quality is closely related to the microbial ecology of grape and fermentation as well as to the used of selected strains to guide the winemaking. The importance of microbial species that develop during fermentation determine the types and concentrations of many substances that may contribute to the good fermentation, aroma and flavor characteristics, and also the safety of wine. Results and Discussion: The main goal of this study was to characterize the yeast populations of grape musts produced from biodynamic or organic agriculture by two approaches: genomics and proteomics. The suitability of MALDI-TOF-MS Biotyper for the identification of non-clinical samples was verified. The genomics was performed by using PCR reaction (Sanger sequencing) with the amplification of ITS region and the proteomics was carried out through MALDI-TOF-MS Biotyper. About 130 isolated strains from fermenting must were identified and both MALDI-TOF MS Biotyper and sequencing showed a more complex yeast population of spontaneously fermented products compared to driven fermentation. The sequencing identified all the tested strains while the MALDI TOF MS Biotyper identified up to the 70-80% of the isolated yeasts, probably due to the incomplete libraries of the instruments. Indeed, this study could support the widening of the libraries with peptide profiles of food interest microorganisms in order to increase the potential applications of the proteomic approach currently limited to clinical areas.

In cystic fibrosis (CF) patients the normal community of commensal bacteria in the gut can be affected by intestinal exocrine alfunction, antibiotic usage and swallowing of infected respiratory mucus. However, CFrelated gut dysbiosis has only recently been subjected to detailed investigation. Herein we report on the integrated metaproteomic, metagenomic and metabolomic workflow for monitoring gut microbiota composition. Twenty-four faecal samples were collected from cystic fibrosis young patients (age range 0-6 years) and 6 faecal samples from healthy children. All samples were processed for peptide, DNA and metabolite analysis. Protein content was analyzed with a shotgun metaproteomic approach by a nano-scale LC-MS2 set-up (Bruker amaZon-ETD) and filtered for operational taxon units (OTUs) assignment. OTUs were corroborated by hybridization of the small subunit ribosomal RNA (SSU rRNA) gene variable regions against the human intestinal tract microarray platform HITChip. In order to evaluate the volatile metabolites a gas-chromatographic (GC)–mass spectrometer (MS)/solid-phase microextraction (SPME) analysis was performed. 1H-NMR spectra were acquired on a Varian 400 MHz Mercury-plus NMR. Pre-analytical steps of the metaproteomics workflow were devised to improve hit coverage, while the OTUs repository was guaranteed by metagenomics entries. 1H-NMR and GC-MS/SPME were used to identify and quantify fecal metabolites. The application of integrated meta-omics-based approaches to the characterization of the membership and dynamics of the polymicrobial communities colonizing the gut is expected to have important predictive potential in translational medicine, specially in CF-related gut dysbiosis.