title: Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder.
abstract: Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.
authors.affiliation: Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Coretti
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cristiano
authors.affiliation: Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Florio
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Napoli, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scala
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lama
authors.affiliation: Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Keller
authors.affiliation: Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Cuomo
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Pero
authors.affiliation: Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Napoli, Italy.
authors.forename: Orlando
authors.initials: O
authors.lastname: Paciello
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mattace Raso
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
authors.affiliation: Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy.|Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cocozza
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Calignano
authors.affiliation: Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy.|Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Chiariotti
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lembo
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000378:metabolism / Q000473:pathology*; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D001522:Behavior, Animal; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000069196:Gastrointestinal Microbiome; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D010641:Phenotype; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: D016207:Cytokines; D012336:RNA, Ribosomal, 16S