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

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

  • Brain Behav Immun. 2023 Feb 27;S0889-1591(23)00050-8. doi: 10.1016/j.bbi.2023.02.019.
Peifeng Guo 1 Xinyu Yang 1 Xiaomeng Guo 2 Huaien Yang 1 Jiao Pan 3 Yue Li 4
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
  • 2 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
  • 3 Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China; Institute of cultural heritage and history of Science & Technology, University of Science and Technology Beijing, Beijing 100083, China.
  • 4 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China. Electronic address: lyue2006@163.com.
Abstract

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.

Keywords

Fragile X syndrome; Gastrointestinal problems; Gut microbes; Omega-3 polyunsaturated fatty acids.

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