Yadav Akanksha, Tadas Manasi, Kale Mayur, Wankhede Nitu, Umekar Milind, Kotagale Nandkishor, Taksande Brijesh
Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur M.S. 441 002, India.
Government College of Pharmacy, Kathora Naka, VMV Road, Amravati M.S. 444604, India.
Physiol Behav. 2025 Jun 10;299:114989. doi: 10.1016/j.physbeh.2025.114989.
Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by deficits in social communication, repetitive behaviors, and restricted interests. Emerging evidence suggests that gut-brain axis a dynamic, bidirectional communication network between gut microbiota and central nervous system, is critical in shaping behavioral ontogeny in ASD. Dysbiosis of gut microbiota, commonly observed in individuals with ASD, has been associated with alterations in neurodevelopmental trajectories and symptom severity. Furthermore, disturbances in maternal microbiome during pregnancy are increasingly recognized as key factors influencing fetal brain development, potentially heightening risk of ASD and behavioral manifestations. Mechanistic research reveals that gut-derived metabolites modulate blood-brain barrier integrity, neuroinflammatory processes, and neuronal circuit formation, contributing to behavioral outcomes. These findings emphasize gut microbiota's profound influence on emergence and progression of ASD-related behaviors. Promising therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, have demonstrated potential in modulating the gut microbiome and improving behavioral symptoms in ASD. However, challenges such as individual variability in microbiome composition, limited clinical evidence, and an incomplete understanding of causative mechanisms remain significant barriers to clinical translation. This review explores the interplay between gut microbiota and ASD-associated behaviors, focusing on key mechanisms such as microbial regulation of neurotransmitter production, immune signaling, and neuroinflammation. It further highlights gut microbiota's potential as a modifiable factor influencing neurodevelopmental and behavioral outcomes in ASD. By advancing our understanding of gut-brain axis, we can pave the way for personalized and targeted interventions aimed at improving behavioral ontogeny and developmental trajectories in individuals with ASD.
自闭症谱系障碍（ASD）是一种多方面的神经发育病症，其特征在于社交沟通缺陷、重复行为和兴趣受限。新出现的证据表明，肠-脑轴作为肠道微生物群与中枢神经系统之间的动态双向通信网络，在塑造ASD的行为个体发育中至关重要。肠道微生物群失调在ASD个体中普遍存在，与神经发育轨迹改变和症状严重程度相关。此外，孕期母体微生物组的紊乱越来越被认为是影响胎儿大脑发育的关键因素，可能会增加患ASD和行为表现的风险。机制研究表明，肠道衍生的代谢产物可调节血脑屏障完整性、神经炎症过程和神经元回路形成，从而影响行为结果。这些发现强调了肠道微生物群对ASD相关行为的出现和进展具有深远影响。包括益生菌、益生元、粪便微生物群移植和饮食干预在内的有前景的治疗策略已显示出调节肠道微生物群和改善ASD行为症状的潜力。然而，诸如微生物组组成的个体差异、有限的临床证据以及对致病机制的不完全理解等挑战仍然是临床转化的重大障碍。本综述探讨了肠道微生物群与ASD相关行为之间的相互作用，重点关注微生物对神经递质产生、免疫信号传导和神经炎症等关键机制的调节。它进一步强调了肠道微生物群作为影响ASD神经发育和行为结果的可调节因素的潜力。通过增进我们对肠-脑轴的理解，我们可以为旨在改善ASD个体行为个体发育和发育轨迹的个性化和靶向干预铺平道路。
