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Propionic acid metabolism, ASD, and vitamin B12: Is there a role for environmental nitrous oxide?
1Institute of Health and Environmental Research, Cleveland, OH 44118, USA.
Insights
Prenatal exposure to propionic acid (PPA) in rats alters behavior, potentially modeling autism spectrum disorder (ASD). This study suggests environmental nitrous oxide (N2O) may trigger PPA overproduction, linking environmental factors to ASD pathogenesis.
Area of Science:
- Neuroscience
- Environmental Health
- Microbiology
Background:
- Prenatal exposure to propionic acid (PPA) in rats has been proposed as an animal model for autism spectrum disorder (ASD).
- Altered gut microbiome composition, favoring PPA-producing microbes, is implicated in ASD, but the underlying cause remains unclear.
- Environmental factors are increasingly recognized for their role in neurodevelopmental disorders.
Purpose of the Study:
- To explore the potential role of environmental nitrous oxide (N2O) in the etiopathogenesis of ASD.
- To investigate the link between N2O exposure, PPA metabolism, and observed behavioral alterations in an ASD animal model.
Main Methods:
- Review and synthesis of existing research on PPA, ASD animal models, and environmental exposures.
- Hypothesizing a mechanism linking N2O exposure to endogenous opioid release and microbial virulence.
- Connecting altered PPA metabolism to N2O-induced changes.
Main Results:
- PPA-treated rat pups exhibit subtle behavioral differences, including in nest seeking, novel object recognition, and locomotor activity.
- Environmental N2O exposure may induce endogenous opioid peptides, conferring a virulence advantage to microbes like Pseudomonas aeruginosa.
- Pathogenic PPA overproduction in ASD may be a compensatory response to N2O-induced microbial virulence.
Conclusions:
- Altered PPA metabolism in ASD may be a consequence of environmental N2O exposure.
- Future research on the PPA model of ASD should consider the impact of environmental N2O.
- N2O represents a novel environmental factor in the etiopathogenesis of ASD and related neuropathology.
Abstract:
Foley et al. (2014) published their findings in this journal on the role of prenatal exposure to propionic acid (PPA) and behavioral outcomes in treated rat pups. The authors show that PPA treated pups displayed subtle differences in behavior including nest seeking, novel object recognition, and locomotor activity. Others have previously proposed that PPA infusion in rat could represent a valid animal model of ASD since many of the diagnostic criteria for the disorder spectrum manifest under such conditions. A pathogenic makeover of gut microbiome to facilitate the growth of microbes capable of producing PPA, like Clostridia species, has been proposed as an infectious contributing etiology to the PPA model of ASD, however the reason for this pathogenic microbial overgrowth is not clear. This discussion highlights a previously identified novel environmental factor (i.e., nitrous oxide, N2O) in the etiopathogenesis of ASD and related neuropathology and posits that altered PPA metabolism in ASD may represent a key manifestation of this particular exposure. Trace environmental exposure to N2O may induce release of endogenous opioid peptides that have been shown to confer a virulence advantage to certain microbes, like Pseudomonas aeruginosa. Pathogenic overproduction of PPA in ASD may be a compensatory mechanism to curb this enhanced virulence potential. Therefore, future research on the PPA model of ASD should consider its role as a consequence of environmental exposure to N2O.
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