Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats

Zhong, Jiugen; Lan, Wan-Ting; Feng, Yanqing; Li, Yinhua; Shen, Yingying; Gong, Jia-Heng; Zou, Zhiyong; Hou, Xiaohui

doi:10.3389/fphys.2023.1077821

Cited by 11 publications

(4 citation statements)

References 57 publications

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“…For example, Liu et al found that acetic acid and butyric acid were decreased in children with ASD ( 8 ). Besides, acetic acid, butyric acid, and valeric acid were significantly decreased in the fecal sample of a valproic acid model of ASD compared to those in the control group ( 31 ). However, the role of SCFAs in ASD pathology remains controversial.…”

Section: Discussionmentioning

confidence: 89%

Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition

et al. 2023

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Short-chain fatty acids (SCFAs, especially butyric acid) have been demonstrated to play a promising role in the development of autism spectrum disorders (ASD). Recently, the hypothalamic–pituitary–adrenal (HPA) axis is also suggested to increase the risk of ASD. However, the mechanism underlying SCFAs and HPA axis in ASD development remains unknown. Here, we show that children with ASD exhibited lower SCFA concentrations and higher cortisol levels, which were recaptured in prenatal lipopolysaccharide (LPS)-exposed rat model of ASD. These offspring also showed decreased SCFA-producing bacteria and histone acetylation activity as well as impaired corticotropin-releasing hormone receptor 2 (CRHR2) expression. Sodium butyrate (NaB), which can act as histone deacetylases inhibitors, significantly increased histone acetylation at the CRHR2 promoter in vitro and normalized the corticosterone as well as CRHR2 expression level in vivo . Behavioral assays indicated ameliorative effects of NaB on anxiety and social deficit in LPS-exposed offspring. Our results imply that NaB treatment can improve ASD-like symptoms via epigenetic regulation of the HPA axis in offspring; thus, it may provide new insight into the SCFA treatment of neurodevelopmental disorders like ASD. IMPORTANCE Growing evidence suggests that microbiota can affect brain function and behavior through the “microbiome–gut–brain’’ axis, but its mechanism remains poorly understood. Here, we show that both children with autism and LPS-exposed rat model of autism exhibited lower SCFA concentrations and overactivation of HPA axis. SCFA-producing bacteria, Lactobacillus , might be the key differential microbiota between the control and LPS-exposed offspring. Interestingly, NaB treatment contributed to the regulation of HPA axis (such as corticosterone as well as CRHR2) and improvement of anxiety and social deficit behaviors in LPS-exposed offspring. The potential underlying mechanism of the ameliorative effect of NaB may be mediated via increasing histone acetylation to the CRHR2 promoter. These results enhance our understanding of the relationship between the SCFAs and the HPA axis in the development of ASD. And gut microbiota-derived SCFAs may serve as a potential therapeutic agent to neurodevelopmental disorders like ASD.

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Section: Discussionmentioning

confidence: 89%

Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition

et al. 2023

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“…Also, many strains of Lactobacillus species are known to produce GABA, ACh and histamine [74] as well as tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in the synthesis of serotonin. Further proof of associations between dysbiosis and changes in neurotransmitters and short-chain fatty acids were observed in a prenatal valproic acid model of ASD [75].…”

Section: Gut Microbiota -Neurotransmittersmentioning

confidence: 79%

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

Tizabi¹,

Bennani²,

Kouhen³

et al. 2023

Preprint

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Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and social communication manifests in early childhood and is followed by significant impairment in social and occupational functions in adolescence and adulthood. Although genetics have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes including anemia, encephalopathy, gastroenteric diseases and more importantly cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as “Gut-Brain Axis (GBA).” In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. Potential exploitation of this interaction for therapeutic purposes is also touched upon.

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“…Also, many strains of Lactobacillus species are known to produce GABA, ACh, and histamine [81], as well as tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in the synthesis of serotonin. Further proof of associations between dysbiosis and changes in neurotransmitters and short-chain fatty acids was observed in a prenatal valproic acid model of ASD [82].…”

Section: Gut Microbiota-neurotransmittersmentioning

confidence: 82%

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

Tizabi,

Bennani,

El Kouhen

et al. 2023

Biomolecules

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Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and communication, manifests in early childhood and is followed by restricted and stereotyped behaviors, interests, or activities in adolescence and adulthood (DSM-V). Although genetics and environmental factors have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes, including anemia, encephalopathy, gastroenteric diseases, and, more importantly, cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as the “Gut–Brain Axis (GBA)”. In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. The potential exploitation of this interaction for therapeutic purposes is also touched upon.

show abstract

Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats

Cited by 11 publications

References 57 publications

Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition

Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

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