Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.

Fang LI; Haoran KE; Siqi Wang; Wei Mao; Cexiong FU; Xi Chen; Qingqing FU; Xiaori Qin; Yonghua Huang; Bidan LI; Shibing LI; Jingying Xing; Minhui Wang; Wenlin Deng

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Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.

Author: Fang LI ¹ ; Haoran KE ² ; Siqi WANG ³ ; Wei MAO ¹ ; Cexiong FU ⁴ ; Xi CHEN ⁵ ; Qingqing FU ⁶ ; Xiaori QIN ¹ ; Yonghua HUANG ¹ ; Bidan LI ⁴ ; Shibing LI ⁷ ; Jingying XING ⁸ ; Minhui WANG ⁹ ; Wenlin DENG ¹⁰
Author Information

1. Department of Gastroenterology, Gastroenterology Endoscopy Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
2. Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
3. Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China.
4. Department of Hepatopancreatobiliary Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
5. Otolaryngology-Head and Neck Surgery, Hospital of Hainan Province, Department of Otorhinolaryngology, Head and Neck Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
6. Department of Radiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
7. Department of Pediatric Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
8. Department of Gastroenterology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
9. Department of Nephrology, Department of Nephrology, Hainan Affiliated Hospital of Hainan Medical College, Hainan General Hospital, Haikou, 570311, China.
10. Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China. dengwl3@mail.sysu.edu.cn.
Publication Type:Journal Article
Keywords: Autism; Gut; Lipopolysaccharide; Metformin; Toll-like receptor 4
MeSH: Mice; Animals; NF-kappa B; Myeloid Differentiation Factor 88/metabolism*; Lipopolysaccharides/pharmacology*; Toll-Like Receptor 4/metabolism*; Autistic Disorder/metabolism*; Signal Transduction/physiology*
From: Neuroscience Bulletin 2023;39(6):911-928
CountryChina
Language:English
Abstract: Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T⁺tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.