Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder

被引:138
作者
Coretti, Lorena [1 ]
Cristiano, Claudia [2 ]
Florio, Ermanno [3 ]
Scala, Giovanni [4 ]
Lama, Adriano [2 ]
Keller, Simona [3 ]
Cuomo, Mariella [3 ]
Russo, Roberto [2 ]
Pero, Raffaela [3 ]
Paciello, Orlando [5 ]
Raso, Giuseppina Mattace [2 ]
Meli, Rosaria [2 ]
Cocozza, Sergio [1 ,3 ]
Calignano, Antonio [2 ]
Chiariotti, Lorenzo [1 ,3 ]
Lembo, Francesca [2 ]
机构
[1] CNR, IEOS, Via S Pansini, I-80131 Naples, Italy
[2] Univ Naples Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy
[3] Univ Naples Federico II, Dept Med Mol & Biotecnol Med, Via S Pansini 5, I-80131 Naples, Italy
[4] Ist Nazl Fis Nucl, Sez Napoli, Naples, Italy
[5] Univ Naples Federico II, Dept Vet Med & Anim Prod, Naples, Italy
关键词
T PLUS TF/J; PSYCHOLOGICAL STRESS; MURINE MODEL; CHILDREN; BRAIN; FECES; FLEXIBILITY; PHENOTYPES; C57BL/6J; STRAINS;
D O I
10.1038/srep45356
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 BTBRT + 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.
引用
收藏
页数:10
相关论文
共 51 条
[1]   Differences in BTBR T plus tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors [J].
Amodeo, Dionisio A. ;
Jones, Joshua H. ;
Sweeney, John A. ;
Ragozzino, Michael E. .
BEHAVIOURAL BRAIN RESEARCH, 2012, 227 (01) :64-72
[2]   The Role of Psychological Stress in Inflammatory Bowel Disease: Quality Assessment of Methods of 18 Prospective Studies and Suggestions for Future Research [J].
Camara, Rafael J. A. ;
Ziegler, Roger ;
Begre, Stefan ;
Schoepfer, Alain M. ;
von Kaenel, Roland .
DIGESTION, 2009, 80 (02) :129-139
[3]   Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability [J].
Cani, P. D. ;
Possemiers, S. ;
Van de Wiele, T. ;
Guiot, Y. ;
Everard, A. ;
Rottier, O. ;
Geurts, L. ;
Naslain, D. ;
Neyrinck, A. ;
Lambert, D. M. ;
Muccioli, G. G. ;
Delzenne, N. M. .
GUT, 2009, 58 (08) :1091-1103
[4]   QIIME allows analysis of high-throughput community sequencing data [J].
Caporaso, J. Gregory ;
Kuczynski, Justin ;
Stombaugh, Jesse ;
Bittinger, Kyle ;
Bushman, Frederic D. ;
Costello, Elizabeth K. ;
Fierer, Noah ;
Pena, Antonio Gonzalez ;
Goodrich, Julia K. ;
Gordon, Jeffrey I. ;
Huttley, Gavin A. ;
Kelley, Scott T. ;
Knights, Dan ;
Koenig, Jeremy E. ;
Ley, Ruth E. ;
Lozupone, Catherine A. ;
McDonald, Daniel ;
Muegge, Brian D. ;
Pirrung, Meg ;
Reeder, Jens ;
Sevinsky, Joel R. ;
Tumbaugh, Peter J. ;
Walters, William A. ;
Widmann, Jeremy ;
Yatsunenko, Tanya ;
Zaneveld, Jesse ;
Knight, Rob .
NATURE METHODS, 2010, 7 (05) :335-336
[5]   NONPARAMETRIC MULTIVARIATE ANALYSES OF CHANGES IN COMMUNITY STRUCTURE [J].
CLARKE, KR .
AUSTRALIAN JOURNAL OF ECOLOGY, 1993, 18 (01) :117-143
[6]  
Crawley Jacqueline N, 2012, Dialogues Clin Neurosci, V14, P293
[7]   Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour [J].
Cryan, John F. ;
Dinan, Timothy G. .
NATURE REVIEWS NEUROSCIENCE, 2012, 13 (10) :701-712
[8]   Peroxisome proliferator-activated receptor alpha plays a crucial role in behavioral repetition and cognitive flexibility in mice [J].
D'Agostino, Giuseppe ;
Cristiano, Claudia ;
Lyons, David J. ;
Citraro, Rita ;
Russo, Emilio ;
Avagliano, Carmen ;
Russo, Roberto ;
Raso, Giuseppina Mattace ;
Meli, Rosaria ;
De Sarro, Giovambattista ;
Heisler, Lora K. ;
Calignano, Antonio .
MOLECULAR METABOLISM, 2015, 4 (07) :528-536
[9]   Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified [J].
De Angelis, Maria ;
Piccolo, Maria ;
Vannini, Lucia ;
Siragusa, Sonya ;
De Giacomo, Andrea ;
Serrazzanetti, Diana Isabella ;
Cristofori, Fernanda ;
Guerzoni, Maria Elisabetta ;
Gobbetti, Marco ;
Francavilla, Ruggiero .
PLOS ONE, 2013, 8 (10)
[10]   Alterations of the Intestinal Barrier in Patients With Autism Spectrum Disorders and in Their First-degree Relatives [J].
de Magistris, Laura ;
Familiari, Valeria ;
Pascotto, Antonio ;
Sapone, Anna ;
Frolli, Alessandro ;
Iardino, Patrizia ;
Carteni, Maria ;
De Rosa, Mario ;
Francavilla, Ruggiero ;
Riegler, Gabriele ;
Militerni, Roberto ;
Bravaccio, Carmela .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2010, 51 (04) :418-424