Early Disruption of the Microbiome Leading to Decreased Antioxidant Capacity and Epigenetic Changes: Implications for the Rise in Autism

Currently, 1 out of every 59 children in the United States is diagnosed with autism. While initial research to find the possible causes for autism were mostly focused on the genome, more recent studies indicate a significant role for epigenetic regulation of gene expression and the microbiome. In this review article, we examine the connections between early disruption of the developing microbiome and gastrointestinal tract function, with particular regard to susceptibility to autism. The biological mechanisms that accompany individuals with autism are reviewed in this manuscript including immune system dysregulation, inflammation, oxidative stress, metabolic and methylation abnormalities as well as gastrointestinal distress. We propose that these autism-associated biological mechanisms may be caused and/or sustained by dysbiosis, an alteration to the composition of resident commensal communities relative to the community found in healthy individuals and its redox and epigenetic consequences, changes that in part can be due to early use and over-use of antibiotics across generations. Further studies are warranted to clarify the contribution of oxidative stress and gut microbiome in the pathophysiology of autism. A better understanding of the microbiome and gastrointestinal tract in relation to autism will provide promising new opportunities to develop novel treatment modalities

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder

Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). Subsequent in vivo studies have demonstrated the direct role of altered gut microbes and metabolites in the progression of neurodevelopmental diseases. This review will discuss the most recent advancements in our understanding of the gut microbiome’s clinical significance in regulating blood-brain barrier (BBB) integrity, immunological function, and neurobiological development. In particular, we address the potentially causal role of GBA dysregulation in the pathophysiology of autism spectrum disorder (ASD) through compromising the BBB and immunological abnormalities. A thorough understanding of the complex signaling interactions between gut microbes, metabolites, neural development, immune mediators, and neurobiological functionality will facilitate the development of targeted therapeutic modalities to better understand, prevent, and treat ASD

Central Auditory Processing Disorders in Individuals with Autism Spectrum Disorders

The etiology and the underlying pathogenetic mechanisms of autism spectrum disorders are still largely unknown. This article provides a comprehensive review of the studies that are relevant to autism spectrum disorders and central auditory processing disorders and also discusses the relationship between autism spectrum disorders and central auditory processing disorders in the light of recent studies on this subject, which may provide new pathways in a therapeutic perspective. Several studies confirm that most of the individuals with an autism spectrum disorder have some degree of sensory dysfunction related to disorders of processing auditory, visual, vestibular, and/or tactile stimuli. Among these studies, some have addressed central auditory processing disorders. There is an increasing amount of effort for studies regarding the link between autism spectrum disorders and central auditory processing disorders. Most of the studies investigating central auditory processing disorders in patients with autism spectrum disorders have used electrophysiological measurements such as mismatch negativity and P300 event-related potentials. In addition to these, several studies have reported deterioration in speech perception and expression in patients with autism spectrum disorders, which may also be related to central auditory processing disorders in this unique group of individuals

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder

Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). Subsequent in vivo studies have demonstrated the direct role of altered gut microbes and metabolites in the progression of neurodevelopmental diseases. This review will discuss the most recent advancements in our understanding of the gut microbiome's clinical significance in regulating blood-brain barrier (BBB) integrity, immunological function, and neurobiological development. In particular, we address the potentially causal role of GBA dysregulation in the pathophysiology of autism spectrum disorder (ASD) through compromising the BBB and immunological abnormalities. A thorough understanding of the complex signaling interactions between gut microbes, metabolites, neural development, immune mediators, and neurobiological functionality will facilitate the development of targeted therapeutic modalities to better understand, prevent, and treat ASD

Beneficial Effects of Milk Having A2 β-Casein Protein: Myth or Reality?

ABSTRACT Diet has been shown to play an important role in maintaining normal homeostasis in the human body. Milk and milk products are a major component of the Western diet, but their consumption may predispose sensitive individuals to adverse health outcomes. Current literature about milk products recognizes various bioactive components including lactate, whey protein, and β-casein protein. Specifically, cow milk has 2 major subvariants of its β-casein protein, A1 and A2, due to a single nucleotide difference that changes the codon at position 67. Whereas the A2 polymorphism is unlikely to undergo enzymatic cleavage during digestion, the A1 polymorphism is more likely to undergo enzymatic cleavage resulting in the product peptide β-casomorphin-7, a known μ-opioid receptor agonist. The objective of this article is to review the current understanding of the 2 major β-casein subvariants and their effects on various organ systems that may have an impact on the health of an individual. Synthesis of the current existing literature on this topic is relevant given the increased association of milk consumption with adverse effects in susceptible individuals resulting in a rising interest in consuming milk alternatives. We discuss the influence of the β-casein protein on the gastrointestinal system, endocrine system, nervous system, and cardiovascular system as well as its role in antioxidants and methylation. A1 milk consumption has been associated with enhanced inflammatory markers. It has also been reported to have an opioid-like response that can lead to manifestations of clinical symptoms of neurological disorders such as autism spectrum disorder. On the other hand, A2 milk consumption has been associated with beneficial effects and is easier to digest in sensitive individuals. Further research is warranted to investigate the short- and long-term effects of consumption of A1 β-casein in comparison with milk with A2 β-casein proteins

Altering the gut microbiome to potentially modulate behavioral manifestations in autism spectrum disorders: A systematic review

•An association between autism spectrum disorders (ASD) and gastrointestinal severity has been suggested.•Intervention along the gut-brain-microbiome axis via probiotics and prebiotics is hypothesized to modulate behavior.•Diverse probiotic supplementation with prebiotics performed better than single strain probiotic supplementation.•Multi-pronged interventions are needed to develop preventive and therapeutic strategies for ASD. There is a potential association between gastrointestinal (GI) symptoms and the severity of autism spectrum disorder (ASD). Given this correlation, the possible impact of probiotics and prebiotics have been explored in research studies to modify the gut microbiome and ameliorate behavioral manifestations of ASD via modulating the gut-brain-microbiome axis. This systematic review focuses on the interplay between these factors in altering the behavioral manifestations of ASD. Probiotic supplementation tended to mitigate some of the behavioral manifestations of ASD, with less of a discernible trend on the microbiome level. Studies supplementing multiple probiotic species, such as microbiota transfer therapy, or including prebiotics performed better than single strain supplementation. Our analysis suggests that gut dysbiosis may increase intestinal permeability, leading to more severe GI symptoms and a systemic inflammatory response, which can alter permeability across the blood-brain barrier and synaptogenesis in the brain. Future studies are warranted to understand the precise contribution of altering gut microbiome on clinical manifestations of ASD that will open up avenues to develop preventive and treatment modalities

Transition to Adulthood for Women on the Spectrum: A Brief Narrative Review

Research in the field of autism spectrum disorders (ASD) focuses mainly on school-aged children and male participants. This has left substantial gaps in our understanding of the life course of autistic individuals, particularly autistic females, once they reach adulthood. The objective of this concise narrative review is to discuss the current literature on autistic women with a focus on transitioning to adulthood, specifically in the areas of quality of life, post-secondary education and employment. Given that the evidence so far suggests widely inconsistent findings, we conclude that future research is needed to more carefully elucidate the unique needs of women on the spectrum during the process of transitioning to adulthood, and to identify evidence-based practices that could better support this population