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      The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease

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          Abstract

          Background

          Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors.

          Objective

          To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices.

          Design

          An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines.

          Results and conclusions

          Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.

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          Most cited references67

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          Human gut microbiome viewed across age and geography

          Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ between human populations when viewed from the perspective of component microbial lineages, encoded metabolic functions, stage of postnatal development, and environmental exposures, we characterized bacterial species present in fecal samples obtained from 531 individuals representing healthy Amerindians from the Amazonas of Venezuela, residents of rural Malawian communities, and inhabitants of USA metropolitan areas, as well as the gene content of 110 of their microbiomes. This cohort encompassed infants, children, teenagers and adults, parents and offspring, and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the representation of genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial species assemblages and functional gene repertoires were noted between individuals residing in the USA compared to the other two countries. These distinctive features are evident in early infancy as well as adulthood. In addition, the similarity of fecal microbiomes among family members extends across cultures. These findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of Westernization.
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            Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.

            A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
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              The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

              A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.
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                Author and article information

                Journal
                Gut
                Gut
                gutjnl
                gut
                Gut
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                September 2023
                20 June 2023
                : 72
                : 9
                : 1642-1650
                Affiliations
                [1 ] departmentIBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche , Ringgold_18654Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Roma, Italy
                [2 ] departmentDepartment of Medicine and Ageing Sciences , ”G. d'Annunzio” University of Chieti-Pescara , Chieti, Italy
                [3 ] departmentCenter for Advanced Studies and Technology (CAST) , “G. d'Annunzio” University of Chieti-Pescara , Chieti, Italy
                [4 ] departmentDepartment of Chronic Diseases & Metabolism (CHROMETA) , Ringgold_26657KU Leuven , Leuven, Belgium
                [5 ] departmentDivision of Gastroenterology , Ringgold_36632Rabin Medical Center , Petah Tikva, Israel
                [6 ] departmentDipartimento di Medicina e Chirurgia Traslazionale , Università Cattolica del Sacro Cuore , Roma, Italy
                [7 ] departmentDipartimento di Biotecnologie e Bioscienze , Ringgold_9305University of Milan-Bicocca , Milano, Italy
                [8 ] departmentINSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department , Ringgold_27063Sorbonne Universite , Paris, France
                [9 ] departmentUOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche , Ringgold_18654Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Roma, Italy
                [10 ] departmentDepartment of Laboratory Sciences and Infectious Diseases , Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Roma, Italy
                [11 ] departmentDepartment of Medicine, Division of Gastroenterology, Crohn's and Colitis Center , Ringgold_12235University of Miami Miller School of Medicine , Miami, Florida, USA
                [12 ] departmentDepartment of Gastroenterology , Ringgold_8703The Queen Elizabeth Hospital , Adelaide, South Australia, Australia
                [13 ] departmentIBD Unit , Ringgold_3749Saint Mark's Hospital , Harrow, UK
                [14 ] departmentMicrobiome Treatment Center , Ringgold_1724University of Birmingham , Birmingham, UK
                [15 ] departmentGastroenterology and Liver Services , Concord Repatriation General Hospital , Sydney, New South Wales, Australia
                [16 ] departmentGastroenterology and Endoscopy , IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele , Milano, Italy
                [17 ] departmentDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism , Ringgold_27280Medizinische Universitat Innsbruck , Innsbruck, Austria
                [18 ] departmentDivision of Gastroenterology and Liver Diseases , Ringgold_12304Case Western Reserve University School of Medicine , Cleveland, Ohio, USA
                [19 ] departmentDepartment of Pathology , Ringgold_12304Case Western Reserve University School of Medicine , Cleveland, Ohio, USA
                [20 ] departmentDeparment of Biomedical Sciences , Humanitas University , Pieve Emanuele, Milano, Italy
                [21 ] departmentIBD Center , IRCCS Humanitas Research Hospital , Rozzano, Milano, Italy
                Author notes
                [Correspondence to ] Professor Loris Riccardo Lopetuso, Department of Medicine and Ageing Sciences, ”G. d'Annunzio” University of Chieti-Pescara, Chieti, Italy; lopetusoloris@ 123456gmail.com

                LRL and SD are joint first authors.

                SV and FS are joint senior authors.

                Author information
                http://orcid.org/0000-0002-5747-2055
                http://orcid.org/0000-0001-7758-6466
                http://orcid.org/0000-0003-4396-1613
                http://orcid.org/0000-0003-0935-8853
                http://orcid.org/0000-0002-2914-1822
                http://orcid.org/0000-0002-8318-0515
                http://orcid.org/0000-0002-2857-1812
                http://orcid.org/0000-0001-7341-1351
                http://orcid.org/0000-0002-4235-2579
                http://orcid.org/0000-0002-1571-1548
                http://orcid.org/0000-0002-3626-6148
                http://orcid.org/0000-0001-9942-3019
                http://orcid.org/0000-0001-8334-7541
                Article
                gutjnl-2023-329948
                10.1136/gutjnl-2023-329948
                10423477
                37339849
                0ce23146-4ca2-43a7-aaf9-093f65008709
                © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 27 March 2023
                : 16 May 2023
                Funding
                Funded by: CCF Clinical Research Investigator-Initiated Award;
                Award ID: N/A
                Categories
                Guideline
                1506
                2312
                1507
                Custom metadata
                unlocked
                editors-choice
                free

                Gastroenterology & Hepatology
                inflammatory bowel disease,intestinal microbiology,ulcerative colitis

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