Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders

Zhang, Zhenzhen; Hou, Mengzhuo; Ou, Huaxing; Wang, Daping; Li, Zhifang; Zhang, Huawei; Lu, Jianping

doi:10.3389/fendo.2022.1067529

Cited by 3 publications

(2 citation statements)

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“…This is consistent with the findings of our gene GO analysis. Besides, abnormalities of key genes in the cell junction assembly pathway can cause the development of ASD ( Zhang et al., 2022 ). Through the action of bile acids and SCFAs, gut microbiota can also alter the energy metabolism of intestinal epithelial mitochondria, activate immune system cells, and modulate intestinal epithelial barrier function ( Dunislawska et al., 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota and autism spectrum disorders: a bidirectional Mendelian randomization study

Li,

Liu,

Liu

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundIn recent years, observational studies have provided evidence supporting a potential association between autism spectrum disorder (ASD) and gut microbiota. However, the causal effect of gut microbiota on ASD remains unknown.MethodsWe identified the summary statistics of 206 gut microbiota from the MiBioGen study, and ASD data were obtained from the latest Psychiatric Genomics Consortium Genome-Wide Association Study (GWAS). We then performed Mendelian randomization (MR) to determine a causal relationship between the gut microbiota and ASD using the inverse variance weighted (IVW) method, simple mode, MR-Egger, weighted median, and weighted model. Furthermore, we used Cochran’s Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to identify heterogeneity and pleiotropy. Moreover, the Benjamin-Hochberg approach (FDR) was employed to assess the strength of the connection between exposure and outcome. We performed reverse MR analysis on the gut microbiota that were found to be causally associated with ASD in the forward MR analysis to examine the causal relationships. The enrichment analyses were used to analyze the biological function at last.ResultsBased on the results of IVW results, genetically predicted family Prevotellaceae and genus Turicibacter had a possible positive association with ASD (IVW OR=1.14, 95% CI: 1.00-1.29, P=3.7×10−2), four gut microbiota with a potential protective effect on ASD: genus Dorea (OR=0.81, 95% CI: 0.69-0.96, P=1.4×10−2), genus Ruminiclostridium5 (OR=0.81, 95% CI: 0.69-0.96, P=1.5×10−2), genus Ruminococcus1 (OR=0.83, 95% CI: 0.70-0.98, P=2.8×10−2), and genus Sutterella (OR=0.82, 95% CI: 0.68-0.99, P=3.6×10−2). After FDR multiple-testing correction we further observed that there were two gut microbiota still have significant relationship with ASD: family Prevotellaceae (IVW OR=1.24; 95% CI: 1.09-1.40, P=9.2×10-4) was strongly positively correlated with ASD and genus RuminococcaceaeUCG005 (IVW OR=0.78, 95% CI: 0.67-0.89, P=6.9×10−4) was strongly negatively correlated with ASD. The sensitivity analysis excluded the influence of heterogeneity and horizontal pleiotropy.ConclusionOur findings reveal a causal association between several gut microbiomes and ASD. These results deepen our comprehension of the role of gut microbiota in ASD’s pathology, providing the foothold for novel ideas and theoretical frameworks to prevent and treat this patient population in the future.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota and autism spectrum disorders: a bidirectional Mendelian randomization study

Li,

Liu,

Liu

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Neuroligin, a postsynaptic cell-adhesion molecule, interacts with presynaptic and intracellular partners, such as neurexins and postsynaptic scaffolding proteins, to facilitate synaptic maturation and transmission ( Krueger et al, 2012 ). Patients with ASD have been found to carry mutations in neuroligin-3 ( Nlgn3 ), resulting in an arginine-to-cysteine substitution at the 451st amino acid residue (R451C; Jamain et al, 2003 ; Hosie et al, 2019 ; Zhang et al, 2022 ). GI-related problems, such as diarrhea and chronic gut pain, have also been confirmed in patients with the NL3 R451C genetic mutation ( Hosie et al, 2019 ).…”

Section: Genetic Risk Factors Relevance To Gi Comorbidities In Asdmentioning

confidence: 99%

The enteric nervous system deficits in autism spectrum disorder

Wang,

Tang,

Wei

et al. 2023

Front. Neurosci.

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Gastrointestinal (GI) disorders are common comorbidities in individuals with autism spectrum disorder (ASD), and abnormalities in these issues have been found to be closely related to the severity of core behavioral deficits in autism. The enteric nervous system (ENS) plays a crucial role in regulating various aspects of gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only results in various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, and highlights several high-risk genes for ASD, which are expressed widely in the gut and implicated in gastrointestinal dysfunction among both animal models and human patients with ASD. Furthermore, we provide a brief overview of environmental factors associated with gastrointestinal tract in individuals with autism. This could offer fresh perspectives on our understanding of ASD.

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