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      Gut Microbiota between Environment and Genetic Background in Familial Mediterranean Fever (FMF)

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          Abstract

          The gastrointestinal tract hosts the natural reservoir of microbiota since birth. The microbiota includes various bacteria that establish a progressively mutual relationship with the host. Of note, the composition of gut microbiota is rather individual-specific and, normally, depends on both the host genotype and environmental factors. The study of the bacterial profile in the gut demonstrates that dominant and minor phyla are present in the gastrointestinal tract with bacterial density gradually increasing in oro-aboral direction. The cross-talk between bacteria and host within the gut strongly contributes to the host metabolism, to structural and protective functions. Dysbiosis can develop following aging, diseases, inflammatory status, and antibiotic therapy. Growing evidences show a possible link between the microbiota and Familial Mediterranean Fever (FMF), through a shift of the relative abundance in microbial species. To which extent such perturbations of the microbiota are relevant in driving the phenotypic manifestations of FMF with respect to genetic background, remains to be further investigated.

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          Most cited references191

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          Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.

          Inflammatory caspases (caspase-1, -4, -5 and -11) are critical for innate defences. Caspase-1 is activated by ligands of various canonical inflammasomes, and caspase-4, -5 and -11 directly recognize bacterial lipopolysaccharide, both of which trigger pyroptosis. Despite the crucial role in immunity and endotoxic shock, the mechanism for pyroptosis induction by inflammatory caspases is unknown. Here we identify gasdermin D (Gsdmd) by genome-wide clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 nuclease screens of caspase-11- and caspase-1-mediated pyroptosis in mouse bone marrow macrophages. GSDMD-deficient cells resisted the induction of pyroptosis by cytosolic lipopolysaccharide and known canonical inflammasome ligands. Interleukin-1β release was also diminished in Gsdmd(-/-) cells, despite intact processing by caspase-1. Caspase-1 and caspase-4/5/11 specifically cleaved the linker between the amino-terminal gasdermin-N and carboxy-terminal gasdermin-C domains in GSDMD, which was required and sufficient for pyroptosis. The cleavage released the intramolecular inhibition on the gasdermin-N domain that showed intrinsic pyroptosis-inducing activity. Other gasdermin family members were not cleaved by inflammatory caspases but shared the autoinhibition; gain-of-function mutations in Gsdma3 that cause alopecia and skin defects disrupted the autoinhibition, allowing its gasdermin-N domain to trigger pyroptosis. These findings offer insight into inflammasome-mediated immunity/diseases and also change our understanding of pyroptosis and programmed necrosis.
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            • Record: found
            • Abstract: found
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            Is Open Access

            A human gut microbial gene catalogue established by metagenomic sequencing.

            To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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              Microbial ecology: human gut microbes associated with obesity.

              Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                03 September 2020
                September 2020
                : 11
                : 9
                : 1041
                Affiliations
                [1 ]Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari BA, Italy; agostinodiciaula@ 123456tiscali.it (A.D.C.); leonildebnf@ 123456gmail.com (L.B.)
                [2 ]Section of Medical Genetics, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari BA, Italy; alessandro.stella@ 123456uniba.it
                [3 ]Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; david.wang@ 123456einsteinmed.org
                Author notes
                [* ]Correspondence: piero.portincasa@ 123456uniba.it ; Tel.: +39-80-5478-893
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-5476-7376
                https://orcid.org/0000-0002-9035-6267
                https://orcid.org/0000-0002-5439-7651
                https://orcid.org/0000-0001-5359-1471
                Article
                genes-11-01041
                10.3390/genes11091041
                7563178
                32899315
                76b9d28a-57bb-48e9-98a6-47bf81db06c7
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 July 2020
                : 31 August 2020
                Categories
                Review

                amyloidosis,colchicine,inflammasome,interleukin-1b,mefv
                amyloidosis, colchicine, inflammasome, interleukin-1b, mefv

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