Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders.

Clinical observations suggest that gut and dietary factors transiently
worsen and, in some cases, appear to improve behavioral symptoms in a
subset of persons with autism spectrum disorders (ASDs), but the reason
for this is unclear. Emerging evidence suggests ASDs are a family of
systemic disorders of altered immunity, metabolism, and gene expression.
Pre- or perinatal infection, hospitalization, or early antibiotic
exposure, which may alter gut microbiota, have been suggested as
potential risk factors for ASD. Can a common environmental agent link
these disparate findings? This review outlines basic science and
clinical evidence that enteric short-chain fatty acids (SCFAs), present
in diet and also produced by opportunistic gut bacteria following
fermentation of dietary carbohydrates, may be environmental triggers in
ASD. Of note, propionic acid, a major SCFA produced by ASD-associated
gastrointestinal bacteria (clostridia, bacteroides, desulfovibrio) and
also a common food preservative, can produce reversible behavioral,
electrographic, neuroinflammatory, metabolic, and epigenetic changes
closely resembling those found in ASD when administered to rodents.
Major effects of these SCFAs may be through the alteration of
mitochondrial function via the citric acid cycle and carnitine
metabolism, or the epigenetic modulation of ASD-associated genes, which
may be useful clinical biomarkers. It discusses the hypothesis that ASDs
are produced by pre- or post-natal alterations in intestinal microbiota
in sensitive sub-populations, which may have major implications in ASD
cause, diagnosis, prevention, and treatment.

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