title: Altered gut microbiota in Rett syndrome.
abstract: The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status.
  
  
  
  Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles.
  
  
  
  We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT subjects and contribute to RTT gastrointestinal physiopathology.
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.|Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123, Trento, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Strati
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.|Department of Biology, University of Florence, Via Madonna del Piano 6, 50019, Sesto Fiorentino, Florence, Italy.
authors.forename: Duccio
authors.initials: D
authors.lastname: Cavalieri
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Albanese
authors.affiliation: Neonatal Intensive Care Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Donati
authors.affiliation: Child Neuropsychiatry Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
authors.affiliation: Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123, Trento, Italy.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jousson
authors.affiliation: Child Neuropsychiatry Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.affiliation: Department of Genomics and Biology of Fruit Crop, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pindo
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Renzi
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rizzetto
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Stefanini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139, Florence, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Calabrò
authors.affiliation: Institute of Biometeorology (IBIMET), National Research Council (CNR), Via Giovanni Caproni 8, I-50145, Florence, Italy. c.de.filippo@ibimet.cnr.it.
authors.forename: Carlotta
authors.initials: C
authors.lastname: De Filippo
mesh_terms: D001419:Bacteria / Q000145:classification* / Q000235:genetics; D044822:Biodiversity; D003248:Constipation / Q000473:pathology; D064806:Dysbiosis / Q000382:microbiology*; D005227:Fatty Acids / Q000378:metabolism; D005658:Fungi / Q000145:classification* / Q000235:genetics; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007422:Intestines / Q000382:microbiology*; D055432:Metabolomics / Q000379:methods; D056186:Metagenomics / Q000379:methods; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics / Q000382:microbiology* / Q000503:physiopathology*
chemical_list: D005227:Fatty Acids; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Constipation; Gut microbiota; Intestinal dysbiosis; Metataxonomics; Mycobiota; Rett syndrome; SCFAs