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Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism
- Source :
- EBioMedicine, Vol 24, Iss C, Pp 166-178 (2017), EBioMedicine
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.<br />Highlights • BTBR mice display a reduced abundance of bile-metabolizing Bifidobacterium and Blautia bacterial species in the intestine. • BTBR mice demonstrate deficient bacterial metabolism of bile moieties in the gut. • Changes in the gut microbiota are associated with marked gastrointestinal distress and reduced sociability in BTBR mice. There is growing awareness that the gut microbiome may contribute to gastrointestinal and behavioral symptomatology of autism spectrum disorder (ASD). However, the exact mechanisms by which intestinal bacteria can affect gut-brain axis signaling in autism are as yet poorly understood. Here we explore interactions between intestinal microbiota, gut physiology and behavior in a mouse model of ASD. We show that a reduction in the abundance of particular intestinal bacteria in “autistic” mice is associated with gastrointestinal distress and social behavior deficits. This work supports the concept of targeting the gut microbiota for reversing gastrointestinal symptoms in ASD, and identifies specific plausible targets for microbiota-based interventions.
- Subjects :
- Male
0301 basic medicine
Autism Spectrum Disorder
Gastrointestinal Diseases
Autism
lcsh:Medicine
Disease
Gut flora
Mice
0302 clinical medicine
Gene Regulatory Networks
BTBR
Bifidobacterium
lcsh:R5-920
Bile acid
biology
Gastrointestinal Dysfunction
Microbiota
Tryptophan
General Medicine
Intestines
Autism spectrum disorder
autism spectrum disorder (ASD)
Intestinal transit
lcsh:Medicine (General)
Research Paper
Serotonin
medicine.drug_class
Gut microbiota
BTBR mouse
Intestinal permeability
digestive system
General Biochemistry, Genetics and Molecular Biology
social behavior
Mouse model
Bile Acids and Salts
03 medical and health sciences
mental disorders
medicine
Animals
gut physiology
Autistic Disorder
Bacteria
Serotonin (5-HT)
Gene Expression Profiling
lcsh:R
Intestinal physiology
medicine.disease
biology.organism_classification
Bile acids
Gastrointestinal Tract
Disease Models, Animal
030104 developmental biology
Gene Expression Regulation
Immunology
Commentary
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- EBioMedicine, Vol 24, Iss C, Pp 166-178 (2017), EBioMedicine
- Accession number :
- edsair.doi.dedup.....77fe8520bf1e1205d9abc721142fd153