Zhang Yangyang, Li Hang, Li Bolin, Li Yizhuang, Chai Xuejun, Li Sheng, Xue Xia, Li Honglei, Zhao Yonghong, Tang Youcai, Yin Baoqi, Zhao Pengju, Li Enyao, Feng Pengya
Department of Children Rehabilitation, Henan Key Laboratory of Rehabilitation Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory for Helicobacter Pylori and Digestive Tract Microecology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Microbiol. 2025 Feb 13;16:1535451. doi: 10.3389/fmicb.2025.1535451. eCollection 2025.
Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder, usually accompanied by gut microbiota dysregulation. Gut microbiota homeostasis is considered effective for ASD. Reportedly, decoction (DCHD) can efficiently regulate gut microbiota and inflammation. However, the mechanisms underlying the effects of DCHD in the treatment of ASD remain unclear.
This study investigated the potential effects and mechanisms of DCHD in treating ASD.
In the animal experiment, propionic acid was administered to construct an ASD rat model. The ASD rats were treated with DCHD, and the efficacy was assessed using the behavioral detections, such as open field test, elevated plus maze test, novel object recognition test. Additionally, the levels of IL-6, TNF-, IL-10, T-SOD, MDA, GSH and CAT were determined using kits, and histological staining was used to evaluate brain morphology. Moreover, tight junction proteins (ZO-1 and occludin) expression levels were evaluated using RT-qPCR, whereas Iba1 expression level was assessed by immunofluorescence staining. The 16S rRNA sequencing and metabolomic analysis of feces revealed the potential targets of DCHD against ASD. In a small human trail, the clinical scales ADOS-2 and Autism Behavior Checklist (ABC) assessed autism severity. Gastrointestinal problems and brain function were evaluated based on food intolerance and event-related potential, respectively.
DCHD significantly improved autism-like behaviors and increased antioxidant enzyme activity, decreased inflammation and enhanced the intestinal barrier by the animal experiment. Furthermore, the DCHD treatment altered the gut microbiota profile, with increased probiotics , , , and Further, DCHD increased the beneficial metabolite indole-3-acetate and decreased the cognitive impairment-related metabolites asymmetric dimethylarginine and homogentisic acid. Meanwhile, the small clinical trial revealed that DCHD significantly alleviated the core symptoms of ASD, with decreased ADOS-2 and ABC scale scores. DCHD also decreased the levels of specific egg white/yolk and milk IgG antibodies and shortened the MMN and P3b latencies.
This study demonstrated that DCHD may alleviate ASD via inhibiting oxidative stress, reducing inflammation, and modulating the gut microbiota in rats. Combined with human trial, DCHD may be a promising drug for treating ASD. This study provides a scientific rationale for treating mental disorders related to gut microbiota dysbiosis.
自闭症谱系障碍（ASD）是一种早发性神经发育障碍，通常伴有肠道微生物群失调。肠道微生物群稳态被认为对ASD有效。据报道，柴胡汤（DCHD）可以有效调节肠道微生物群和炎症。然而，DCHD治疗ASD的潜在机制仍不清楚。
本研究探讨DCHD治疗ASD的潜在作用及机制。
在动物实验中，给予丙酸构建ASD大鼠模型。用DCHD治疗ASD大鼠，并通过旷场试验、高架十字迷宫试验、新物体识别试验等行为检测评估疗效。此外，使用试剂盒测定白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、总超氧化物歧化酶（T-SOD）、丙二醛（MDA）、谷胱甘肽（GSH）和过氧化氢酶（CAT）的水平，并采用组织学染色评估脑形态。此外，使用实时定量聚合酶链反应（RT-qPCR）评估紧密连接蛋白（闭合蛋白和闭锁蛋白）的表达水平，而通过免疫荧光染色评估离子钙结合衔接分子1（Iba1）的表达水平。粪便的16S核糖体RNA测序和代谢组学分析揭示了DCHD治疗ASD的潜在靶点。在一项小型人体试验中，使用临床量表孤独症诊断观察量表第二版（ADOS-2）和儿童自闭症行为量表（ABC）评估自闭症严重程度。分别基于食物不耐受和事件相关电位评估胃肠道问题和脑功能。
动物实验表明，DCHD显著改善了自闭症样行为，提高了抗氧化酶活性，减轻了炎症，并增强了肠道屏障。此外，DCHD治疗改变了肠道微生物群谱，益生菌、、、和增加。此外，DCHD增加了有益代谢物吲哚-3-乙酸，并降低了与认知障碍相关的代谢物不对称二甲基精氨酸和尿黑酸。同时，小型临床试验表明，DCHD显著缓解了ASD的核心症状，降低了ADOS-2和ABC量表评分。DCHD还降低了特异性蛋清/蛋黄和牛奶IgG抗体水平，并缩短了失匹配负波（MMN）和P3b潜伏期。
本研究表明，DCHD可能通过抑制氧化应激、减轻炎症和调节大鼠肠道微生物群来缓解ASD。结合人体试验，DCHD可能是一种有前景的治疗ASD的药物。本研究为治疗与肠道微生物群失调相关的精神障碍提供了科学依据。
