Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders

MacFabe, Derrick F.; Cain, Donald P.; Rodríguez-Capote, Karina; Franklin, Andrew E.; Hoffman, Jennifer; Boon, Francis; Taylor, Alison R.; Kavaliers, Martin; Ossenkopp, Klaus‐Peter

doi:10.1016/j.bbr.2006.07.025

Cited by 425 publications

(439 citation statements)

References 183 publications

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“…While the etiologic factors in most patients with symptoms in the autistic disorder spectrum are not fully understood, changes in amino acid metabolism and organic acid concentrations have been reported in animal models mimicking autistic symptoms [6,7]. Furthermore, amino acid levels in autistic patients have been reported as significantly different from non-autistic control groups [3,5,14].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, studies evaluating the effects of elevated propionic acid in rats have suggested a possible connection with autism [6,7]. Propionic acid administered systemically or by intracebro-ventricular injection to adult rats produced a rapid induction of repetitive movements, hyperactive activity, and seizure activity along with neuro-pathological and biochemical similarities to human ASD [6].…”

Section: Introductionmentioning

confidence: 99%

“…Propionic acid administered systemically or by intracebro-ventricular injection to adult rats produced a rapid induction of repetitive movements, hyperactive activity, and seizure activity along with neuro-pathological and biochemical similarities to human ASD [6]. The mechanisms by which elevated levels of propionic acid affect the CNS are unknown, but possible candidates include interference with cellular metabolism, increased inflammatory cytokines and the reduction of intercellular gap-junctional communication.…”

Section: Introductionmentioning

confidence: 99%

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Autism in patients with propionic acidemia

Witters

Debbold

Crivelly

et al. 2016

Molecular Genetics and Metabolism

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Certain inborn errors of metabolism have been suggested to increase the risk of autistic behavior. In an animal model, propionic acid ingestion triggered abnormal behavior resembling autism. So far only a few cases were reported with propionic acidemia and autistic features. From a series of twelve consecutively diagnosed cases with propionic acidemia, we report on eight patients with autistic features. The patients were followed 2-4 times a year and underwent regular clinical, dietary and laboratory investigations. Psychological evaluation was performed every second to fourth year. All patients were compliant with the standard diet and carnitine supplementation. None of the patients had frequent metabolic decompensations. From the metabolic factors known to impact neuropsychological outcome we detected chronically decreased valine levels and altered valine to leucine ratios in five out of the eight patients. Recurrent lactic acid elevations were present in six out of the eight patients. Five of the eight patients were diagnosed with Autism Spectrum Disorder, four of them had pathogenic variants in PCCB. Disorder according to DSM-IV and/or DSM-5 criteria. One of the patients diagnosed with propionic acidemia by newborn screening had the most significant behavioral features and another was diagnosed with Autism Spectrum Disorder prior to propionic acidemia. We hypothesize that chronic suboptimal intracellular metabolic balance may be responsible for the increased risk for autistic features in propionic acidemia. We propose that patients diagnosed with propionic acidemia should be screened for Autism Spectrum Disorder.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autism in patients with propionic acidemia

Witters

Debbold

Crivelly

et al. 2016

Molecular Genetics and Metabolism

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“…43,49 Interestingly, short-term treatment with antibiotics has been reported to improve behavioral symptoms in some patients with autism. 50 Probiotics and novel therapies targeted at gut dysbiosis show promise for treatment of ASD, however, more studies are needed to better define these novel therapeutic strategies.…”

Section: The Association Between Intestinal Microbiome and The Brain-mentioning

confidence: 99%

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

Saulnier¹,

et al. 2013

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The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro-and prebiotics.

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“…Their study showed that interruption in the normal composition of native gut flora resulted colonization of some neurotoxin producing bacteria, contributing to the autistic symptom. As the importance of gut microbiota in gut-brain function came emerging; probable role of diet, bacteria and enzyme became a field of important study in autism research [180]. It has been proved that there is a significant difference between the stool sample from autistic and normal children in terms of frequency of occurrence of four bacterial phyla specifically viz.…”

Section: B) Neurodegenerative Illnessmentioning

confidence: 99%

Commensal Bugs from the Gut-Shaping Human Health and Disease

Chowdhury¹

2014

JIG

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Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders

Cited by 425 publications

References 183 publications

Autism in patients with propionic acidemia

Autism in patients with propionic acidemia

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

Commensal Bugs from the Gut-Shaping Human Health and Disease

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