Zhong Jiu-Gen, Lan Wan-Ting, Feng Yan-Qing, Li Yin-Hua, Shen Ying-Ying, Gong Jia-Heng, Zou Zhi, Hou Xiaohui
School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China.
School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Front Physiol. 2023 Mar 22;14:1077821. doi: 10.3389/fphys.2023.1077821. eCollection 2023.
The microbiota-gut-brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats. The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC). The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and . Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with , and at the genus level, and they were also related to the decrease of short-chain fatty acids. According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota-gut-brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.
微生物群-肠-脑轴在自闭症谱系障碍的病理生理学中起着重要作用，但其具体机制仍不清楚。本研究旨在探讨丙戊酸模型大鼠中神经递质和短链脂肪酸的变化与肠道微生物群改变之间的关联。通过产前暴露于丙戊酸（VPA）建立自闭症模型大鼠。进行莫里斯水迷宫试验、旷场试验和三室试验以评估大鼠的行为。从粪便样本中提取的16S rRNA基因序列用于评估肠道微生物组成。采用气相色谱-质谱联用和液相色谱-质谱联用技术鉴定粪便样本中的短链脂肪酸和前额叶皮质（PFC）中的神经递质。结果显示，鉴定出丙戊酸模型大鼠和对照大鼠之间有28个细菌分类群，丙戊酸模型大鼠和对照大鼠中差异最大的细菌分类群属于宏基因组物种。与对照大鼠相比，丙戊酸模型大鼠中的乙酸、丁酸、戊酸、异丁酸和异戊酸显著降低。与对照大鼠相比，丙戊酸模型大鼠前额叶皮质中的五种神经递质（苏氨酸、犬尿氨酸、色氨酸、5-羟吲哚乙酸，记为5-HIAA，以及氯化甜菜碱醛，记为BAC）显著降低，而甜菜碱增加。多种神经递质（≥4种）与属水平的 和 相关，并且它们也与短链脂肪酸的减少有关。根据本研究，我们可以初步推断肠道微生物群或其代谢产物（如短链脂肪酸）可能通过肠-脑轴的相关途径影响中枢神经递质代谢。这些结果为理解微生物群-肠-脑轴在自闭症谱系障碍中的作用提供了微生物和短链脂肪酸（SCFA）框架，并为自闭症谱系障碍的治疗提供了新的思路。
