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.