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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.
Afiliação
  • Cuomo M; Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
  • Coretti L; CEINGE Advanced Biotechnologies "Franco Salvatore", Via G. Salvatore 482, 80145, Naples, Italy.
  • Costabile D; Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.
  • Della Monica R; CEINGE Advanced Biotechnologies "Franco Salvatore", Via G. Salvatore 482, 80145, Naples, Italy.
  • De Riso G; SEMM-European School of Molecular Medicine, University of Naples "Federico II", Naples, Italy.
  • Buonaiuto M; Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
  • Trio F; CEINGE Advanced Biotechnologies "Franco Salvatore", Via G. Salvatore 482, 80145, Naples, Italy.
  • Bravaccio C; Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
  • Visconti R; Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
  • Berni Canani R; CEINGE Advanced Biotechnologies "Franco Salvatore", Via G. Salvatore 482, 80145, Naples, Italy.
  • Chiariotti L; Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
  • Lembo F; CEINGE Advanced Biotechnologies "Franco Salvatore", Via G. Salvatore 482, 80145, Naples, Italy.
Sci Rep ; 13(1): 18197, 2023 10 24.
Article em En | MEDLINE | ID: mdl-37875530
ABSTRACT
The gut-brain axis involves several bidirectional pathway communications including microbiome, bacterial metabolites, neurotransmitters as well as immune system and is perturbed both in brain and in gastrointestinal disorders. Consistently, microbiota-gut-brain axis has been found altered in autism spectrum disorder (ASD). We reasoned that such alterations occurring in ASD may impact both on methylation signatures of human host fecal DNA (HFD) and possibly on the types of human cells shed in the stools from intestinal tract giving origin to HFD. To test this hypothesis, we have performed whole genome methylation analysis of HFD from an age-restricted cohort of young children with ASD (N = 8) and healthy controls (N = 7). In the same cohort we have previously investigated the fecal microbiota composition and here we refined such analysis and searched for eventual associations with data derived from HFD methylome analysis. Our results showed that specific epigenetic signatures in human fecal DNA, especially at genes related to inflammation, associated with the disease. By applying methylation-based deconvolution algorithm, we found that the HFD derived mainly from immune cells and the relative abundance of those differed between patients and controls. Consistently, most of differentially methylated regions fitted with genes involved in inflammatory response. Interestingly, using Horvath epigenetic clock, we found that ASD affected children showed both epigenetic and microbiota age accelerated. We believe that the present unprecedented approach may be useful for the identification of the ASD associated HFD epigenetic signatures and may be potentially extended to other brain disorders and intestinal inflammatory diseases.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Espectro Autista / Microbioma Gastrointestinal Limite: Child / Child, preschool / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Espectro Autista / Microbioma Gastrointestinal Limite: Child / Child, preschool / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article