Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long–Evans rat: Further development of a rodent model of autism

Shultz, Sandy R.; MacFabe, Derrick F.; Martin, Samantha; Jackson, Jordana; Taylor, Roy; Boon, Francis; Ossenkopp, Klaus‐Peter; Cain, Donald P.

doi:10.1016/j.bbr.2008.12.023

Cited by 124 publications

(84 citation statements)

References 55 publications

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“…Furthermore, they found increased oxidative stress markers in the brain and reported the presence of neuroinfl ammation indicators. Similar experimental setups support these fi ndings and provide more evidence for abnormalities in brain and behavior [172][173][174]. These data fi t well to the observation that the fecal SCFA concentrations are elevated in children with autism spectrum disorder [124].…”

Section: Propionic Acidsupporting

confidence: 81%

Reevaluating the hype: four bacterial metabolites under scrutiny

Fröhlich

Mayerhofer

Holzer

2015

European Journal of Microbiology and Immunology

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With microbiome research being a fiercely contested playground in science, new data are being published at tremendous pace. The review at hand serves to critically revise four microbial metabolites widely applied in research: butyric acid, flagellin, lipoteichoic acid, and propionic acid. All four metabolites are physiologically present in healthy humans. Nevertheless, all four are likewise involved in pathologies ranging from cancer to mental retardation. Their inflammatory potential is equally friend and foe. The authors systematically analyze positive and negative attributes of the aforementioned substances, indicating chances and dangers with the use of pre-and probiotic therapeutics. Furthermore, the widespread actions of microbial metabolites on distinct organs and diseases are reconciled. Moreover, the review serves as critical discourse on scientific methods commonly employed in microbiome research and comparability as well as reproducibility issues arising thereof.

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Section: Propionic Acidsupporting

confidence: 81%

Reevaluating the hype: four bacterial metabolites under scrutiny

Fröhlich

Mayerhofer

Holzer

2015

European Journal of Microbiology and Immunology

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“…As a weak acid, PPA exists in both aqueous and lipid soluble forms; it crosses the blood-brain barrier both passively and actively through specific monocarboxylate transporters (Thomas et al 2010). Intracerebroventricular injection of PPA in adult rats produced behavioral, biochemical, electrophysiological, and neuropathological effects similar to those observed in autism (MacFabe et al 2007Shultz et al 2009Shultz et al , 2008. Following intracerebroventricular infusions of PPA, there was an evidence of a relationship between changes in brain lipid profiles and the occurrence of autistic behaviors (Thomas et al 2010).…”

Section: Discussionmentioning

confidence: 85%

Autism Spectrum Disorder in a Child with Propionic Acidemia

et al. 2012

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Autism is a neurodevelopmental disorder characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interests. While autism does not have an identifying cause in most of the cases, it is associated with known medical conditions in at least 10% of cases. Although uncommon, cases of autism have also been reported in association with metabolic disorders. In this brief report, we describe the occurrence of autism in a 7-year-old girl with propionic acidemia (PA), a common form of organic aciduria resulting from the deficiency of propionyl-CoA carboxylase and characterized by frequent and potentially lethal episodes of metabolic acidosis often accompanied by hyperammonemia. It is particularly common in countries with high rates of consanguinity. Early diagnosis of autism in patients with metabolic disorders is important since autistic features are sometimes the most disruptive of all the child's problems. This facilitates providing the needed behavioral services not otherwise available for children with metabolic disorders.

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“…Neuroinflammation (astrogliosis) was evident in these animals (Shultz et al, 2008). This same treatment also impaired cognition and sensorimotor ability in Long-Evans rats (Shultz et al, 2009;Shultz et al, 2015).…”

Section: Asd and Gut Microbiome Animal Model Studiesmentioning

confidence: 85%

Microbiome Disturbances and Autism Spectrum Disorders

2015

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Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined.

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Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long–Evans rat: Further development of a rodent model of autism

Cited by 124 publications

References 55 publications

Reevaluating the hype: four bacterial metabolites under scrutiny

Reevaluating the hype: four bacterial metabolites under scrutiny

Autism Spectrum Disorder in a Child with Propionic Acidemia

Microbiome Disturbances and Autism Spectrum Disorders

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