(digestive system) Group of organs stretching from the mouth to the anus, serving to breakdown foods, assimilate nutrients, and eliminate waste; in humans, the digestive system includes the gastrointestinal tract (mouth, esophagus, stomach, intestines, anus) and the accessory glands (liver, biliary tract, pancreas), and associated hormones and secretions. – National Institutes of Health
Excerpt:
“intensifying evidence confirms that much of what ASD involves is related not to a static encephalopathy-based model of autism but rather to the consequences of environmental insult and complex and dynamic psychological and physiological processes involving the interdependence of the nervous, immune, and host microbiome.”
Conclusion: The totality of evidence supports a multifactorial model of ASD in which genetic predisposition, neuroimmune biology, environmental toxicants, perinatal stressors, and iatrogenic exposures converge to produce the phenotype of a post-encephalitic state. Combination and early-timed routine childhood vaccination constitutes the most significant modifiable risk factor for ASD, supported by convergent mechanistic, clinical, and epidemiologic findings, and characterized by intensified use, the clustering of multiple doses during critical neurodevelopmental windows, and the lack of research on the cumulative safety of the full pediatric schedule. As ASD prevalence continues to rise at an unprecedented pace, clarifying the risks associated with cumulative vaccine dosing and timing remains an urgent public health priority.
Excerpts:
“We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles.”
“We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.”
Excerpts:
“Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms.”
“Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.”
Abstract
The gut microbiome profile of a child with autism spectrum disorder (ASD) and co-occurring gastrointestinal (GI) symptoms was compared to that of her healthy triplet siblings to determine if she exhibited intestinal dysbiosis. Shotgun metagenomic sequencing was performed in individual fecal samples, and relative microbial abundance and diversity was determined. Microbial diversity was lower in sibling #3, coupled with a higher Bacteroidetes/Firmicutes ratio, a lower relative abundance of Actinobacteria, and an increased relative abundance of Proteobacteria. Our findings are suggestive of gut dysbiosis in a child with ASD and co-occurring GI symptoms, compared to her two healthy triplet siblings.
Excerpt:
“Accumulating evidence implies the gut-brain axis as a pathway for MeHg harmful neurotoxic effects and a potential factor for later neurodegenerative disorders. The MeHg may induce a hormesis-related neuronal toxicity. Hormesis is an important redox dependent aging-associated neurodegenerative/ neuroprotective issue (Calabrese et al., 2010). The use of antioxidants, such as plant polyphenols (Calabrese et al., 2010; Leri et al., 2020) and protective nutrients (Oria et al., 2020) may be beneficial in reducing the MeHg-driven neuroinflammatory state and associated cell death with the interplay of the intestinal microbiota.”
“Background: Encephalitis, the inflammation of the brain, may be caused by an infection or an autoimmune reaction.”
“Conclusion: Gut microbiota disruption was observed in encephalitis patients, which manifested as pathogen dominance and health-promoting commensal depletion. Disease severity and brain damage may have associations with the gut microbiota or its metabolites.”
Excerpts:
“Herein, we will discuss the accumulating literature for ASD, giving special attention to the relevant aspects of factors that may be related to the neuroimmune interface in the development of ASD, including changes in neuroplasticity.”
Commentary on the article:
“The authors rightly highlight the newest challenging frontier of autism research: the neuroimmune axis alterations. These alterations are first evident in the cells early responsible for immune responses, as they are the precursors for macrophages, dendritic, and microglial cells: monocytes or peripheral blood mononuclear cells (PBMCs). These cells show strong dysfunctions in ASD children and are committed to a pro-inflammatory state, which in turn result in long-term immune alterations (4). In ASDs, altered PBMCs are responsible for elevated pro-inflammatory cytokine production. The up-regulation of inflammatory cytokines is also reflected in brain centers of autistic patients (5): the consequences are the induction of blood–brain barrier (the immunological interface between peripheral immune system and central nervous system) disruption. Changes in BBB permeability directly influence neural plasticity, connectivity and function, triggering impairments in social interaction, communication, and behavior (3). Immunological abnormalities also influence the gastrointestinal system and the microglial innate immune cells of the central nervous system (6). The authors also discuss the role of autoimmunity in the pathogenesis of autism. Familial or virus/bacteria-infected autoimmunity could be a risk factor for autism. Even if the exact cellular and molecular pathways responsible for the induction of neuroimmune alterations are still to be further clarify, a complex interaction among epigenetic and environmental risk factors (7) could trigger the neuroimmune abnormalities, such as abnormal neuron and glia responses.”
Excerpt:
“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.”
Excerpts:
“The likelihood of the child having ASD more than doubled among children with food allergy compared with those without food allergy; children with respiratory and skin allergy were also significantly more likely to have ASD, but at a lesser magnitude. While no sex difference was found for food allergy, boys with ASD were significantly more likely than girls with ASD to have respiratory and skin allergy.”
” It may be that GI dysfunction, seizures, and sleep disorder, in addition to food, respiratory, and skin allergies, are medical comorbidities that characterize the immune-mediated subtype of ASD.”
“In the Discussion section of their article, Xu and colleagues review other aspects of immune dysfunction reported in ASD, including abnormalities in peripheral immunoglobulins, imbalance of T-cell subsets, and increased levels of proinflammatory cytokines in postmortem brains of patients with ASD. Considering the significant association between food, respiratory, and skin allergy in children with ASD reported by Xu and colleagues, in conjunction with numerous studies documenting aspects of immune dysfunction in patients with ASD and specific animal models of ASD, evidence continues to mount that an immune-mediated subtype of ASD should continue to be pursued and defined.”
