Francesco Strati1,2, Duccio Cavalieri1,3, Davide Albanese1, Claudio De Felice4, Claudio Donati1, Joussef Hayek5, Olivier Jousson2, Silvia Leoncini5, Massimo Pindo6, Daniela Renzi7, Lisa Rizzetto1, Irene Stefanini1, Antonio Calabrò7, Carlotta De Filippo8. 1. Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all' Adige, Italy. 2. Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123, Trento, Italy. 3. Department of Biology, University of Florence, Via Madonna del Piano 6, 50019, Sesto Fiorentino, Florence, Italy. 4. Neonatal Intensive Care Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy. 5. Child Neuropsychiatry Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy. 6. 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. 7. Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139, Florence, Italy. 8. Institute of Biometeorology (IBIMET), National Research Council (CNR), Via Giovanni Caproni 8, I-50145, Florence, Italy. c.de.filippo@ibimet.cnr.it.
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
Constipation; Gut microbiota; Intestinal dysbiosis; Metataxonomics; Mycobiota; Rett syndrome; SCFAs
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