Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder

MacFabe, Derrick F.; Cain, Nathan E.; Boon, Francis; Ossenkopp, Klaus‐Peter; Cain, Donald P.

doi:10.1016/j.bbr.2010.10.005

Cited by 316 publications

(250 citation statements)

References 62 publications

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“…40 Butyric acid also acts as a potent inhibitor of histone deacetylase (HDAC) activity, 41 and in rats, propionic acid treatments result in ASD behaviors. [42][43][44] Previously, several neurological effects of propionic acid in rats have been reported by Finegold et al 14,21 The correlations between metabolically active bacterial genera and the metabolomic data are described and reported in Figure 3. Bifidobacterium is negatively and positively correlated with propionic and butyric acids, respectively.…”

Section: Short Chain Fatty Acid (Scfa) Profiling In Asdsmentioning

confidence: 88%

Autism spectrum disorders and intestinal microbiota

et al. 2015

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Section: Short Chain Fatty Acid (Scfa) Profiling In Asdsmentioning

confidence: 88%

Autism spectrum disorders and intestinal microbiota

et al. 2015

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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%

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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“…129 Propionic acid, a SFCA that is produced by gut microbiota can also induce significant changes in social development and behavior and create a similar picture to ASD. 130,131 Intraventricular administration of propionic acids to rats can cause structural abnormalities similar to those found in patients with ASD. 132,133 Some of these findings have parallels in humans.…”

Section: Emerging Areasmentioning

confidence: 97%

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Yarandi

Peterson

Treisman

et al. 2016

J Neurogastroenterol Motil

223

134

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Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

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Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder

Cited by 316 publications

References 62 publications

Autism spectrum disorders and intestinal microbiota

Autism spectrum disorders and intestinal microbiota

Autism in patients with propionic acidemia

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

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