Sex-specific differences in the gut microbiota and fecal metabolites in an adolescent valproic acid-induced rat autism model

Gu, You-Yu; Han, Ying; Liang, Jingjing; Cui, Yanan; Zhang, Bi; Zhang, Ying; Zhang, Shaobin; Qin, Jiong

doi:10.52586/5051

Cited by 10 publications

(6 citation statements)

References 65 publications

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“…In this way, the effect of SMPS on the VPA-induced intestinal flora of model rats can be more accurately explored. Through 16S rRNA gene sequencing analysis, we found that the richness and diversity of the GM showed significant differences among the SMPS, VPA and control rats, which is consistent with the findings of a previous study (Gu et al, 2021). A recent report found that the richness and diversity of gut microbiota did not differ between VPA and control groups, while the overall composition of gut microbiota was significantly different (Gu et al, 2022).…”

Section: Discussionsupporting

confidence: 90%

Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats

Yang

Zhang

et al. 2022

Front. Microbiol.

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Stigma maydis polysaccharide (SMPS) is a plant polysaccharide that participates in immune regulation and gastrointestinal motility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders, and ASD patients often present intestinal microflora imbalance problems; however, there is no effective treatment method. This study explores the effect of SMPS intervention on the gut microbiota in autism model rats as well as the potential action pathways. Female Wistar rats were intraperitoneally injected with sodium valproic acid (VPA) or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. The offspring prenatally exposed to VPA were randomly assigned to the VPA and the SMPS groups. The SMPS group was administered SMPS from E0.5 to postnatal day (PND) 21. We performed 16S rRNA and transcriptomics analyses to reveal the gut microbiota (GM) and differentially expressed genes in the autism model rats in response to SMPS intervention. SMPS intervention significantly improved the diversity and structure of the GM in autism model rats compared with the VPA rats. Moreover, the relative abundance of Prevotellaceae and Lachnospiraceae_NK4A136_group was increased after SMPS intervention. Transcriptome sequencing showed that 496 differentially expressed genes (DEGs) were identified after SMPS administration compared with the VPA group. Meanwhile, gene ontology (GO) enrichment analysis of DEGs was showed that the SMPS group had significant 653 GO terms. SMPS intervention had a major influence on oxidative phosphorylation, retrograde endocannabinoid signaling, thermogenesis, ribosome, protein digestion and absorption, renin-angiotensin system, calcium signaling pathway, glycosphingolipid biosynthesis-ganglio series, and propanoate metabolism pathways. Overall, this study suggests that SMPS interventions in early life may have an impact on gut microbiota, and then affect the transcriptomics levels of the hippocampal tissue in the VPA-induced autism model rats. It provides scientific evidence for the role of the microbe-gut-brain axis in ASD research.

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Section: Discussionsupporting

confidence: 90%

Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats

Yang

Zhang

et al. 2022

Front. Microbiol.

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“…A strong correlation between gut microbiota and fatty acids has been reported in autistic rats [98]. In terms of specific fatty acid, mice injected with valproic acid showed higher abundance of Candidatus_Saccharimonas which suggests a direct link between gut microbiota and fecal metabolites [99]. In line with our results, a positive regulation between Parabacteroides and SCFAs has been demonstrated in human fecal microbiota identified by in vitro fermentation [100].…”

Section: Discussionsupporting

confidence: 89%

Annexin-A1 deficiency attenuates stress-induced tumor growth via fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis

Cui¹,

Sachaphibulkij²,

Teo³

et al. 2022

Theranostics

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Background: High emotional or psychophysical stress levels have been correlated with an increased risk and progression of various diseases. How stress impacts the gut microbiota to influence metabolism and subsequent cancer progression is unclear. Methods: Feces and serum samples from BALB/c ANXA1 +/+ and ANXA1 -/-mice with or without chronic restraint stress were used for 16S rRNA gene sequencing and GC-MS metabolomics analysis to investigate the effect of stress on microbiome and metabolomics during stress and breast tumorigenesis. Breast tumors samples from stressed and non-stressed mice were used to perform Whole-Genome Bisulfite Sequencing (WGBS) and RNAseq analysis to construct the potential network from candidate hub genes. Finally, machine learning and integrated analysis were used to map the axis from chronic restraint stress to breast cancer development. Results:We report that chronic stress promotes breast tumor growth via a stress-microbiomemetabolite-epigenetic-oncology (SMMEO) axis. Chronic restraint stress in mice alters the microbiome composition and fatty acids metabolism and induces an epigenetic signature in tumors xenografted after stress. Subsequent machine learning and systemic modeling analyses identified a significant correlation among microbiome composition, metabolites, and differentially methylated regions in stressed tumors. Moreover, silencing Annexin-A1 inhibits the changes in the gut microbiome and fatty acid metabolism after stress as well as basal and stress-induced tumor growth. Conclusions: These data support a physiological axis linking the microbiome and metabolites to cancer epigenetics and inflammation. The identification of this axis could propel the next phase of experimental discovery in further understanding the underlying molecular mechanism of tumorigenesis caused by physiological stress.

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“…To investigate sexual dimorphism of VPA effects, several studies have compared gender-specific alterations in maternally VPA-treated offspring [19][20][21][22][23]. Evidence shows gender-specific changes in the immune responses [19,20,22,24], cell density of cerebellum [23,25], network connectivity [26], anandamide signaling [27], attentional processing [28], and composition of gut microbiota [29] in maternally VPA-treated animal offspring. These sexual dimorphisms may be related to histone deacetylase (HDAC) inhibition by VPA, as Konopko et al have reported differential epigenetic modification of Bdnf genes in maternally VPA-treated fetal brains of different genders [24].…”

Section: Vpa-induced Asd-like Animal Modelsmentioning

confidence: 99%

Pathophysiological Studies of Monoaminergic Neurotransmission Systems in Valproic Acid-Induced Model of Autism Spectrum Disorder

Kuo

Liu

2022

Biomedicines

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology. The core syndromes of ASD are deficits in social communication and self-restricted interests and repetitive behaviors. Social communication relies on the proper integration of sensory and motor functions, which is tightly interwoven with the limbic function of reward, motivation, and emotion in the brain. Monoamine neurotransmitters, including serotonin, dopamine, and norepinephrine, are key players in the modulation of neuronal activity. Owing to their broad distribution, the monoamine neurotransmitter systems are well suited to modulate social communication by coordinating sensory, motor, and limbic systems in different brain regions. The complex and diverse functions of monoamine neurotransmission thus render themselves as primary targets of pathophysiological investigation of the etiology of ASD. Clinical studies have reported that children with maternal exposure to valproic acid (VPA) have an increased risk of developing ASD. Extensive animal studies have confirmed that maternal treatments of VPA include ASD-like phenotypes, including impaired social communication and repetitive behavior. Here, given that ASD is a neurodevelopmental disorder, we begin with an overview of the neural development of monoaminergic systems with their neurochemical properties in the brain. We then review and discuss the evidence of human clinical and animal model studies of ASD with a focus on the VPA-induced pathophysiology of monoamine neurotransmitter systems. We also review the potential interactions of microbiota and monoamine neurotransmitter systems in ASD pathophysiology. Widespread and complex changes in monoamine neurotransmitters are detected in the brains of human patients with ASD and validated in animal models. ASD animal models are not only essential to the characterization of pathogenic mechanisms, but also provide a preclinical platform for developing therapeutic approaches to ASD.

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Sex-specific differences in the gut microbiota and fecal metabolites in an adolescent valproic acid-induced rat autism model

Cited by 10 publications

References 65 publications

Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats

Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats

Annexin-A1 deficiency attenuates stress-induced tumor growth via fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis

Pathophysiological Studies of Monoaminergic Neurotransmission Systems in Valproic Acid-Induced Model of Autism Spectrum Disorder

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