GW4064 Alters Gut Microbiota Composition and Counteracts Autism-Associated Behaviors in BTBR T+tf/J Mice
Autism spectrum disorder (ASD) is considered a heterogeneous neurodevelopmental disorder characterized by significant social, communication, and behavioral impairments. The gut microbiota is increasingly considered a promising therapeutic target in ASD. Farnesoid X receptor (FXR) has recently been s...
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Published in | Frontiers in cellular and infection microbiology Vol. 12; p. 911259 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
22.06.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Autism spectrum disorder (ASD) is considered a heterogeneous neurodevelopmental disorder characterized by significant social, communication, and behavioral impairments. The gut microbiota is increasingly considered a promising therapeutic target in ASD. Farnesoid X receptor (FXR) has recently been shown to modulate the gut microbiota. We hypothesized that FXR agonist GW4064 could ameliorate behavioral deficits in an animal model for autism: BTBR T
+
Itpr3
tf
/J (BTBR) mouse. As expected, administration of GW4064 rescued the sociability of BTBR mice in the three-chamber sociability test and male-female social reciprocal interaction test, while no effects were observed in C57BL/6J mice. We also found that GW4064 administration increased fecal microbial abundance and counteracted the common ASD phenotype of a high Firmicutes to Bacteroidetes ratio in BTBR mice. In addition, GW4064 administration reversed elevated
Lactobacillus
and decreased
Allobaculum
content in the fecal matter of BTBR animals. Our findings show that GW4064 administration alleviates social deficits in BTBR mice and modulates selective aspects of the composition of the gut microbiota, suggesting that GW4064 supplementation might prove a potential strategy for improving ASD symptoms. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Andreas Martin Grabrucker, University of Limerick, Ireland Reviewed by: Lorena Coretti, University of Naples Federico II, Italy; Jared Schwartzer, Mount Holyoke College, United States This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology |
ISSN: | 2235-2988 2235-2988 |
DOI: | 10.3389/fcimb.2022.911259 |