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Brain, Behavior, and Immunity
Volume 110, 2023, Pages 140-151

Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome

Peifeng Guoa, Xinyu Yanga, Xiaomeng Guob

Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.


Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by a lack of the fragile X mental retardation protein (FMRP). Individuals with neurodevelopmental disorders frequently experience gastrointestinal problems that are primarily linked to gut microbial dysbiosis, inflammation, and increased intestinal permeability. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are non-pharmacological agents that exert potential therapeutic effects against neurological disorders. However, it is unclear whether omega-3 PUFAs improve autistic behaviors in fragile X syndrome (FXS) by altering the gut microbial composition. Here, we describe gastrointestinal problems in Fmr1 knockout (KO) mice. FMRP deficiency causes intestinal homeostasis dysfunction in mice. Fish oil (FO) as a source of omega-3 PUFAs reduces intestinal inflammation but increases the mRNA and protein levels of TJP3 in the colon of juvenile Fmr1 KO mice. Fecal microbiota transplantation from FO-fed Fmr1 KO mice increased the gut abundance of Akkermansia and Gordonibacter in recipient Fmr1 KO mice and improved gut homeostasis and autistic behaviors. Our findings demonstrate that omega-3 PUFAs improve autistic behaviors and gut homeostasis in FMRP-deficient mice by suppressing gut microbiota dysbiosis, thereby presenting a novel therapeutic approach for juvenile FXS treatment.

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