Exploring the Association Between Human Blood Metabolites and Autism Spectrum Disorder Risk: A Bidirectional Mendelian Randomization Study

Health Science Reports, Journal Year: 2025, Volume and Issue: 8(3)

Published: March 1, 2025

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with poorly understood etiology. Recent studies have suggested that metabolic dysregulation might be linked to the development of ASD; however, causal relationships remain unclear. This study aimed investigate association between these factors using two-sample Mendelian randomization (TSMR). We conducted TSMR analysis assess relationship blood metabolites and ASD summarized GWAS data. The metabolite dataset from Canadian Longitudinal Study Aging included 1091 309 ratios 7824 European individuals. data Psychiatric Genomics Consortium comprised 18,381 cases 27,969 controls. Blood were set as exposures outcome. primarily used inverse-variance weighted method, supplemented by MR-Egger, median, simple mode, mode methods. also sensitivity analyses confirm robustness. Replication, confounding, reserve performed verify causation. Additionally, pathway network pharmacology explore potential mechanisms. identified 55 known including 13 10 unknown associated ASD. our pathways, among which tryptophan metabolism was most notable (p = 0.0388). Gene Ontology functional Kyoto Encyclopedia Genes Genomes highlighted crucial such cellular glucuronidation, glucuronosyltransferase activity, bile secretion, significance apical part cell. Our findings indicate dodecenedioate, methionine sulfone, cysteine alanine ratio proline glutamate an impact on These results enhance understanding pathways involved in could lead new avenues for intervention prevention. Further research needed mechanisms underlying associations different populations.

Language: Английский

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Synbiotics of encapsulated Limosilactobacillus fermentum K73 promotes in vitro favorable gut microbiota shifts and enhances short-chain fatty acid production in fecal samples of children with autism spectrum disorder

Food Research International, Journal Year: 2025, Volume and Issue: unknown, P. 116227 - 116227

Published: March 1, 2025

Modulation of the gut microbiota has emerged as a promising approach for addressing gastrointestinal and neurodevelopmental symptoms associated with autism spectrum disorder (ASD). Consequently, this study aimed to evaluate impact four formulated synbiotics comprising Limoscilactobacillus fermentum K73, high-oleic palm oil whey, on composition Colombian children without ASD. These components were encapsulated through high-shear emulsification spray drying. The their individual subjected in vitro digestion fermentation using samples microbiota. Short-chain fatty acids (SCFAs), including lactic, acetic, propionic, butyric acids, quantified HPLC-DAD, while serotonin was determined by an ELISA kit after fermentations. Changes microbial structure assessed sequencing 16S rRNA gene via next-generation (NGS). results revealed decrease abundance genera like Bacteroides Dorea ASD-associated treatment synbiotics. Conversely, increase relative probiotic-related genera, Lactobacillus, Streptococcus, Anaerostipes, observed. Furthermore, analysis SCFAs indicated that synbiotic intervention resulted elevated acid synthesis, alongside propionic acid, which is changes considered beneficial context This evidence suggests L. K73 could represent live biotherapeutic strategy modulating

Language: Английский

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Associations of Microbiome Pathophysiology with Social Activity and Behavior are Mediated by Epigenetic Modulations: Avenues for Designing Innovative Therapeutic Strategies

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106208 - 106208

Published: May 1, 2025

Language: Английский

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Aberration of social behavior and gut microbiota induced by cross-fostering implicating the gut-brain axis

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 120, P. 499 - 512

Published: June 27, 2024

Language: Английский

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Behavioral decline in Shank3Δex4–22 mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes

Molecular Autism, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 4, 2024

Abstract Background SHANK3 , a gene encoding synaptic scaffolding protein, is implicated in autism spectrum disorder (ASD) and disrupted Phelan-McDermid syndrome (PMS). Despite evidence of regression or worsening ASD-like symptoms individuals with PMS, the underlying mechanisms remain unclear. Although Shank3 highly expressed cerebellar cortical granule cells, its role function contribution to behavioral deficits ASD models are unknown. This study investigates changes alterations Δex4–22 mice at two developmental stages. Methods wildtype, heterozygous, homozygous knockout lacking exons 4–22 (all functional isoforms) were subjected battery both juvenile (5–7 weeks old) adult (3–5 months mouse cohorts sexes. Immunostaining was used show expression cortex. Spontaneous excitatory postsynaptic currents (sEPSCs) from cells (CGCs) recorded by whole-cell patch-clamp electrophysiology. Results Deletion caused motor function, heightened anxiety, repetitive behaviors. These genotype-dependent more prominent than juveniles. Reduced social preference only identified male mice, while self-grooming uniquely elevated males across age groups. Heterozygous showed little no phenotypes most tests. Immunofluorescence staining indicated presence predominantly dendrite-containing rosette-like structures CGCs, colocalizing presynaptic markers glutamatergic mossy fiber. Electrophysiological findings parallel relationship between age-related exacerbation impairments enhancement sEPSC amplitude CGCs. Limitations Other tests muscle strength (grip test), memory (Barnes/water maze), communication (ultrasonic vocalization), not performed. Further necessary elucidate how modulates fiber-granule cell synapse cerebellum whether these shape phenotype. Conclusions Our reveal an mutant mice. results suggest that may alter receptors fiber-cerebellar as potential mechanism causing disruption ASD.

Language: Английский

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Fecal microbiota transplantation from individual with bipolar disorder and healthy control elicits distinct behaviors and metabolite profiles in mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 16, 2023

Abstract Bipolar disorder (BD) is a chronic mood characterized by recurrent episodes of depression and (hypo-) mania. The gut microbiome potential avenue through which metabolic signaling, inflammatory pathways, environmental factors, genetics influence BD pathogenesis via the gut-brain axis. Fecal microbiota transplantation (FMT) powerful translational tool for investigating connections between BD, there evidence FMT can transfer affective symptoms from humans to mice. In this study, we compared behavior, metabolomic profiles, marker expression in two groups adult female C57BL/6J mice, one receiving human donor with mixed episode ( HAM-D = 20, YMRS 14) another mentally healthy weight age-matched control without (HAM-D 0). Here, demonstrate that mice individuals had an increased abundance Bacteroidota decreased abundances Parabacteroides merdae Akkermansia muciniphila associated altered levels fecal metabolites, short-chain fatty acids, related hormone relative FMT. also exhibited differential regulation several metabolites markers amygdala, glycine being most prominently affected. Furthermore, displayed anxiety-like behavior sociability, indicating aspects behavioral phenotype are transferable Taken together, these findings implicate signaling physiological changes observed our BD-FMT mouse model.

Language: Английский

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Colony-stimulating factor 2 (CSF2) as a gut microbiome dependent immune factor that alters molecular and behavioral responses to cocaine in male mice

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 122, P. 137 - 149

Published: Aug. 3, 2024

Language: Английский

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Gut–brain communication through microbes

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 29 - 66

Published: Jan. 1, 2024

Language: Английский

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Acetate enhances spatial memory in females via sex- and brain region-specific epigenetic and transcriptional remodeling

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Metabolic control of chromatin and gene expression is emerging as a key, but largely unexplored aspect regulation. In the brain, metabolic-epigenetic interactions can influence critical neuronal functions. Here, we use combination behavioral, proteomic genomic approaches to demonstrate that intermediary metabolite acetate enhances memory in brain region- sex-specific manner. We show facilitates formation dorsal hippocampus-dependent spatial memories female not male mice, while having no effect on cortex-dependent non-spatial either sex. Acetate-enhanced driven by increased acetylation histone variant H2A.Z, upregulation genes implicated learning hippocampus mice. line with behavioral outcomes, hippocampal modifications shows marked differences between sexes during windows (consolidation recall). Overall, our findings elucidate novel role for acetate, ubiquitous abundant metabolite, regulating chromatin, learning, outline exposure promising new approach enhance formation.

Language: Английский

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Metataxonomic and Immunological Analysis of Feces from Children with or without Phelan–McDermid Syndrome

Microorganisms, Journal Year: 2024, Volume and Issue: 12(10), P. 2006 - 2006

Published: Oct. 2, 2024

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay and autism spectrum (ASD)-like behaviors. Emerging research suggests link between gut microbiota neuropsychiatric conditions, including PMS. This study aimed to investigate the fecal immune profiles of children with PMS compared healthy controls. Fecal samples were collected from diagnosed age-matched The bacterial composition was analyzed using 16S rRNA gene sequencing, while short-chain fatty acids (SCFAs) quantified through gas chromatography. Immunological profiling conducted multiplex cytokine assay. Significant differences observed in patients controls, lower abundance key genera such as

Language: Английский

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