Host fecal DNA specific methylation signatures mark gut dysbiosis and inflammation in children affected by autism spectrum disorder

Cuomo, Mariella; Coretti, Lorena; Costabile, Davide; Della Monica, Rosa; De Riso, Giulia; Buonaiuto, Michela; Trio, Federica; Bravaccio, Carmela; Visconti, Roberta; Berni Canani, Roberto; Chiariotti, Lorenzo; Lembo, Francesca

doi:10.1038/s41598-023-45132-0

Cited by 4 publications

(1 citation statement)

References 58 publications

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“…The study found that specific epigenetic features in the DNA of gut microbes in human feces, particularly those associated with inflammation, are strongly associated with disease ( 59 ). In our study, we found some possible inflammatory cytokine pathways in the gut microbiota associated with the epigenetic clock.…”

Section: Discussionmentioning

confidence: 99%

Genetic association of the gut microbiota with epigenetic clocks mediated by inflammatory cytokines: a Mendelian randomization analysis

Tian,

Liao,

Chen

et al. 2024

Front. Immunol.

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BackgroundA new aging biomarker epigenetic clock has been developed. There exists a close link between aging and gut microbiota, which may be mediated by inflammatory cytokines. However, the relationship between the epigenetic clock, gut microbiota, and the mediating substances is unclear.MethodsTwo large genome-wide association meta-analyses were analyzed by two-sample Mendelian randomization. The results between gut microbiota and epigenetic clock were investigated using the four methods (Inverse variance weighted, MR-Egger, weighted median, MR-PRESSO). Genetic correlation was measured by Linked disequilibrium score regression (LDSC). The correctness of the study direction was checked by the Steiger test. Cochran’s Q statistic and MR-Egger intercept were used as sensitivity analyses of the study. The two-step method was used to examine the mediating role of inflammatory cytokines. We use the Benjamini-Hochberg correction method to correct the P value.ResultsAfter FDR correction, multiple bacterial genera were significantly or suggestively associated with four epigenetic clocks (GrimAge, HannumAge, IEAA, PhenoAge). And we detected several inflammatory factors acting as mediators of gut microbiota and epigenetic clocks.ConclusionThis study provides genetic evidence for a positive and negative link between gut microbiota and aging risk. We hope that by elucidating the genetic relationship and potential mechanisms between aging and gut microbiota, we will provide new avenues for continuing aging-related research and treatment.

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Section: Discussionmentioning

confidence: 99%

Genetic association of the gut microbiota with epigenetic clocks mediated by inflammatory cytokines: a Mendelian randomization analysis

Tian,

Liao,

Chen

et al. 2024

Front. Immunol.

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Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Zarimeidani,

Rahmati,

Mostafavi

et al. 2024

Inflammation

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder. Graphical Abstract

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Intercontinental insights into autism spectrum disorder: a synthesis of environmental influences and DNA methylation

Kuodza,

Kawai,

LaSalle

2024

Environmental Epigenetics

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by a broad range of symptoms. The etiology of ASD is thought to involve complex gene-environment interactions, which are crucial to understanding its various causes and symptoms. DNA methylation is an epigenetic mechanism that potentially links genetic predispositions to environmental factors in the development of ASD. This review provides a global perspective on ASD, focusing on how DNA methylation studies may reveal gene-environment interactions characteristic of specific geographical regions. It delves into the role of DNA methylation in influencing the causes and prevalence of ASD in regions where environmental influences vary significantly. We also address potential explanations for the high ASD prevalence in North America, considering lifestyle factors, environmental toxins, and diagnostic considerations. Asian and European studies offer insights into endocrine-disrupting compounds (EDC), persistent organic pollutants (POP), maternal smoking, and their associations with DNA methylation alterations in ASD. In areas with limited data on DNA methylation and ASD, such as Africa, Oceania, and South America, we discuss prevalent environmental factors based on epidemiological studies. Additionally, the review integrates global and country-specific prevalence data from various studies, providing a comprehensive picture of the variables influencing ASD diagnoses over region and year of assessment. This prevalence data, coupled with regional environmental variables and DNA methylation studies, provides a perspective on the complexities of ASD research. Integrating global prevalence data, we underscore the need for a comprehensive global understanding of ASD’s complex etiology. Expanded research into epigenetic mechanisms of ASD is needed, particularly in underrepresented populations and locations, to enhance biomarker development for diagnosis and intervention strategies for ASD that reflect the varied environmental and genetic landscapes worldwide.

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Host fecal DNA specific methylation signatures mark gut dysbiosis and inflammation in children affected by autism spectrum disorder

Cited by 4 publications

References 58 publications

Genetic association of the gut microbiota with epigenetic clocks mediated by inflammatory cytokines: a Mendelian randomization analysis

Genetic association of the gut microbiota with epigenetic clocks mediated by inflammatory cytokines: a Mendelian randomization analysis

Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Intercontinental insights into autism spectrum disorder: a synthesis of environmental influences and DNA methylation

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