Introduction: 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.Methods: 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).Results: 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 Lactobacillus intestinalis. 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 Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids.Discussion: 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.

BackgroundNeuroinflammation is closely associated with the occurrence and development of autism spectrum disorder (ASD). This study aims to describe the global development history and current status of neuroinflammation in ASD from 2004 to 2021 and reveal the research hotspots and frontiers to provide a reference for scholars in related fields to carry out further research.MethodsJournal articles on ASD and neuroinflammation-related research were obtained from the Web of Science Core Collection (WOSCC) database from its inception to 2021. Literature was analyzed visually by VOSviewer, CiteSpace, and R language, including publication analysis, author, institution, national/regional cooperative network analysis, and keyword analysis. We screened the most accumulatively cited 10 experimental papers in the field and the most cited 10 experimental papers in the last 2 years (2020 and 2021) for combing.ResultsA total of 620 publications were included in this study, and the number of publications has increased in recent years. The United States (256, 41.29%) was the country with the largest number of publications. King Saud University (40, 6.45%) was the most published institution; Laila Al-Ayadhi Yousef was the most published researcher; the Brain Behavior and Immunity was the main journal for the study of neuroinflammation in autism, having published 22 related articles. Keyword co-occurrence analysis showed that short chain fatty acid, mast cells, and glial cells have been the focus of recent attention. Burst keywords show that gut microbiota and immune system are the future research trends.ConclusionThis bibliometric study describes the basic framework for the development in the field of neuroinflammation and ASD through an exploration of key indicators (countries, institutions, journals, authors, and keywords). We found that the key role of neuroinflammation in the development of ASD is attracting more and more researchers’ attention. Future studies can investigate the changes in cytokines and glial cells and their related pathways in ASD neuroinflammation. Immunotherapy to inhibit neuroinflammation may be intensively studied as a direction for ASD treatment or intervention.