Gastrointestinal symptoms and autism spectrum disorder: links and risks – a possible new overlap syndrome

Abstract

Autism spectrum disorder (ASD) is a genetically determined neurodevelopmental brain disorder presenting with restricted, repetitive patterns of behaviors, interests, and activities, or persistent deficits in social communication and social interaction. ASD is characterized by many different clinical endophenotypes and is potentially linked with certain comorbidities. According to current recommendations, children with ASD are at risk of having alimentary tract disorders – mainly, they are at a greater risk of general gastrointestinal (GI) concerns, constipation, diarrhea, and abdominal pain. GI symptoms may overlap with ASD core symptoms through different mechanisms. These mechanisms include multilevel pathways in the gut–brain axis contributing to alterations in behavior and cognition. Shared pathogenetic factors and pathophysiological mechanisms possibly linking ASD and GI disturbances, as shown by most recent studies, include intestinal inflammation with or without autoimmunity, immunoglobulin E-mediated and/or cell-mediated GI food allergies as well as gluten-related disorders (celiac disease, wheat allergy, non-celiac gluten sensitivity), visceral hypersensitivity linked with functional abdominal pain, and dysautonomia linked with GI dysmotility and gastroesophageal reflux. Dysregulation of the gut microbiome has also been shown to be involved in modulating GI functions with the ability to affect intestinal permeability, mucosal immune function, and intestinal motility and sensitivity. Metabolic activity of the microbiome and dietary components are currently suspected to be associated with alterations in behavior and cognition also in patients with other neurodegenerative diseases. All the above-listed GI factors may contribute to brain dysfunction and neuroinflammation depending upon an individual patient’s genetic vulnerability. Due to a possible clinical endophenotype presenting as comorbidity of ASD and GI disorders, we propose treating this situation as an “overlap syndrome”. Practical use of the concept of an overlap syndrome of ASD and GI disorders may help in identifying those children with ASD who suffer from an alimentary tract disease. Unexplained worsening of nonverbal behaviors (agitation, anxiety, aggression, self-injury, sleep deprivation) should alert professionals about this possibility. This may shorten the time to diagnosis and treatment commencement, and thereby alleviate both GI and ASD symptoms through reducing pain, stress, or discomfort. Furthermore, this may also protect children against unnecessary dietary experiments and restrictions that have no medical indications. A personalized approach to each patient is necessary. Our understanding of ASDs has come a long way, but further studies and more systematic research are warranted.

ASDmiR: A Stepwise Method to Uncover miRNA Regulation Related to Autism Spectrum Disorder

“…Functional enrichment analysis results show that 439 GO terms and 128 KEGG pathways are significantly associated with the target genes of the hub miRNAs. Moreover, several significantly enriched GO biological processes and KEGG pathways, including Cell cycle arrest (GO: 0007050), Regulation of immune response (GO: 0050776) ( Gupta et al, 2014 ) ( Ander et al, 2015 ), Nervous system development (GO:0007399) ( Hu et al, 2017 ), NF-kappa B signaling pathway (hsa04064) ( Malik et al, 2011 ), Long-term depression (hsa04730) ( Monday et al, 2018 ), Wnt signaling pathway (hsa04310) ( Shen et al, 2016 ), and gastric cancer (hsa05226) ( Wasilewska and Klukowski, 2015 ) are closely associated with the progression and development of ASD ( Figure 4B ). As for the identified hub miRNA sponges, functional enrichment analysis results indicate that they are significantly enriched in SMAD binding (GO: 0046332).…”

“…In Table 2 , several GO, KEGG, Reactome, Disease Ontology, DisGeNET, and Network of Cancer Genes terms are closely associated with ASD. For instance, severe depression (umls: C0588008) ( Hedley et al, 2018 ), Mild cognitive disorder (umls: C1270972) ( Leekam, 2016 ), acute gastroenteritis (umls: C0267446) ( Wasilewska and Klukowski, 2015 ), Focal adhesion (GO: 0005925) ( Ander et al, 2015 ), long-term memory (GO: 0007616) ( Toichi and Kamio, 2002 ), and spliceosome (hsa03040) ( Kong et al, 2013 ) are experimentally confirmed to be ASD-related terms. Taken together, the above enrichment analysis results indicate that the identified miRNA-associated modules are functional.…”

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach

“…Expected prevalence of ASD at 18–24 months in first-degree relatives is 14.7% [ 9 ], so in this study we estimate 73 ASD diagnoses. The expected prevalence of GI symptoms in an ASD population is 60% [ 80 ], so we anticipate 44 of the 73 ASD diagnosed infants to also present GI symptoms.…”

Otizm Spektrum Bozukluğuna Moleküler Bakış: Genetik ve İmmünolojik Etmenler ile Bağırsak Mikrobiyotası üzerine Bulgular

“…Otistik çocuklarda GİS bozuklukların ve inflamasyonun görülme sıklığının artmış olduğu 90,91 ; hastaların % 91'inde GİS bozuklukları saptandığı bildirilmiştir 92 . Son çalışmalar bağırsak fonksiyon bozuklukları ile OSB arasında bir ilişki olabileceğini ve hastalık semptomlarının şiddetinde GİS faktörünün önemli olabileceğini öne sürmektedir [93][94][95] . Bazı otistik çocuklarda karın ağrısı, ishal, kabızlık ve şişkinlik gibi GİS bozuklukları sıklıkla görülmektedir.…”