Fecal DNA methylation signatures marking gut dysbiosis and inflammation in children affected by autism spectrum disorders

ABSTRACT: Gut brain axis involves several bidirectional pathways 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 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 and healthy controls. For the same cohort we have previously investigated the fecal microbiota composition and fecal fatty acids levels, and these data were here utilized for specific correlation analyses. Our results showed that specific epigenetic signatures in human fecal DNA, especially at inflammation-related genes, 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 epigenetic signatures and may be potentially extended to other brain disorders and intestinal inflammatory diseases.

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST1180 | biostudies-other |

REPOSITORIES: biostudies-other