Microbiome Disturbances and Autism Spectrum Disorders

Abstract

Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined.

Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?

“…Interestingly, a diverse number of metabolites generated by the gut microbiota can impact serotonin production and, in this manner, participate in the gut-brain axis to form the microbiota-gut-brain axis. As described in this issue (Rosenfeld, 2015), however, the gut microbiota also generates metabolites, such as 4-ethylphenylsulfate, SCFA, and ammonia, which may exert adverse neurobehavioral effects. With this in mind, Rosenfeld examines the interplay that exists within the microbiota-gut-brain axis and queries whether gut dysbiosis and aberrant gut metabolism may lead to autism-like disturbances.…”

From Epidemiology to Epigenetics: Evidence for the Importance of Nutrition to Optimal Health Development Across the Life Course

“…Patients with various mental health disorders appear to experience alterations in the stability, structure, and composition of fecal microbiota (Jiang et al 2015;Mayer et al 2014a), which in turn affect the severity of their disease. Scientists speculate that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain through bidirectional signaling between the brain and the gut microbiome involving multiple neurocrine and endocrine signaling mechanisms (Mayer et al 2014b;Wang and Kasper 2014;Rosenfeld 2015). This research starts to bring together the effects that the microbiome has not only on physical health but also on mental and emotional health.…”

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“…At the genus level, significant reductions were found between children with ASD compared with non affected controls in the relative abundance of Prevotella, Coprococcus, Enterococcus, Lactobacillus, Streptococcus, Lactococcus, Staphylococcu , Ruminococcus, and Bifidobacterium species in [38][39][40][41][42][43][44]. Conversely, especially Clostridia spp.…”

“…Thus, food influences the composition of the microbiome, which affects the production of SCFAs and thereby the intestinal membrane integrity. SCFA-producing bacteria, e.g., Clostridia, Desulfovibrio, and Bacteroides, are increased in feces of children with ASD [39][40][41][42][43][44]. Clostridium species and Lactobacillus species were increased in the stool of affected children and these bacterial species are known to influence serotonin (5-HT) and catecholamines metabolism with increased 5-HT levels in whole blood and platelets, and together altered function and metabolism of neurotransmitters, and dysfunction of the serotonergic system have been reported to contribute to symptomatology of ASD [5,8,15,19,25,26,35].…”

“…The microbiota profiles from healthy siblings of ASD patients are generally found to be an intermediate between the ASD cases and unaffected controls [45]. Associations were found between long-term diets and the presence of different enterotypes.For example, the presence of Bacteroides spp, a bacterial species is linked to a diet high in fat and animal protein [35,[38][39][40][41][42][43][44]. Thus, food influences the composition of the microbiome, which affects the production of SCFAs and thereby the intestinal membrane integrity.…”