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Microbiome–Epigenome Interactions in Early-Life Molecular Programming

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1386

Editors


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Guest Editor
Institute of Agrochemisty and Food Technology, National Research Council (IATA-CSIC), 46980 Valencia, Spain
Interests: microbiota; pregnancy; breast milk; early life; nutrition; host-microbe interaction

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Guest Editor Assistant
Department of Neonatology, Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Interests: microbiome; epigenome; early life; molecular programming

Special Issue Information

Dear Colleagues,

Early life represents a sensitive developmental window during which environmental cues exert durable molecular effects on human health. Among these cues, the microbiome and the epigenome form a tightly interconnected regulatory axis that shapes gene expression programs essential for immune maturation, metabolic regulation, neurodevelopment, and barrier function. Microbial metabolites and structural components act as molecular signals capable of inducing stable epigenetic modifications, including DNA methylation, histone remodeling, and non-coding RNA–mediated regulation, while host epigenetic landscapes reciprocally influence microbial colonization and functional ecosystem assembly.

This Special Issue focuses on the molecular and mechanistic foundations of microbiome–epigenome interactions driving early-life programming from fetal development through infancy. Core thematic areas include microbiome-driven epigenetic regulation; DNA methylation and histone modifications induced by microbial signaling; non-coding RNAs at the host–microbiome interface; placental microbiome–epigenome communication; epigenetic control of immune and intestinal barrier development; metabolic and neurodevelopmental programming; and integrative multi-omics and systems biology approaches. Both adaptive developmental processes and maladaptive programming associated with adverse intrauterine or early postnatal environments are within scope.

By integrating molecular biology, epigenomics, and microbiome science, this Special Issue aims to elucidate how early environmental signals become biologically embedded at the molecular level, with particular emphasis on molecular biomarkers and translational targets relevant for early preventive strategies.

Dr. Maria Carmen Collado
Guest Editor

Dr. Miljana Zivojin Jovandaric
Guest Editor Assistant

Manuscript Submission Information

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Keywords

  • early-life programming
  • microbiome–epigenome axis
  • DNA methylation
  • histone modification
  • microbial metabolites
  • non-coding RNAs
  • immune maturation
  • placental and postnatal development

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Published Papers (1 paper)

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Research

20 pages, 595 KB  
Article
Microbiome-Derived Short-Chain Fatty Acids and Tryptophan Metabolites in Children with Autism Spectrum Disorder: A Stool–Urine Multi-Omics Analysis
by Joško Osredkar, Teja Fabjan, Uroš Godnov, Maja Jekovec-Vrhovšek, Damjan Osredkar, Petra Finderle, Kristina Kumer, Maša Zorec, Lijana Fanedl and Gorazd Avguštin
Int. J. Mol. Sci. 2026, 27(9), 3988; https://doi.org/10.3390/ijms27093988 - 29 Apr 2026
Viewed by 1044
Abstract
Autism spectrum disorder (ASD) has been associated with alterations in the gut microbiota and its metabolites, particularly short-chain fatty acids (SCFAs) and microbiota-derived tryptophan catabolites, which may influence neurodevelopment through immune and epigenetic mechanisms. We investigated whether stool SCFAs and tryptophan-pathway metabolites differ [...] Read more.
Autism spectrum disorder (ASD) has been associated with alterations in the gut microbiota and its metabolites, particularly short-chain fatty acids (SCFAs) and microbiota-derived tryptophan catabolites, which may influence neurodevelopment through immune and epigenetic mechanisms. We investigated whether stool SCFAs and tryptophan-pathway metabolites differ between children with ASD and typically developing controls, and whether these metabolites associate with ASD severity and systemic biochemical signatures. In this cross-sectional study, we analyzed stool samples from 229 children (160 with ASD, 69 controls) with complete SCFA and tryptophan-metabolite data, while urine metabolomics data were available for a subset and were used for exploratory stool–urine integration analyses. Children with ASD and controls were similar in age, but the ASD group had a higher proportion of males. Absolute concentrations of individual SCFAs, total SCFAs, and derived indices were broadly comparable between groups; nominal differences in propionate/acetate ratio and caproate did not remain significant after false discovery rate correction. Similarly, stool tryptophan-pathway metabolites reported as ng/a.u. based on the NanoDrop-derived proxy (tryptophan, kynurenine, indole-3-acetic, indole-3-lactic, indole-3-propionic, indole-3-aldehyde, N-acetyl-tryptophan, serotonin, melatonin, tryptamine) and functional ratios (kynurenine/tryptophan, indole-derived/tryptophan, serotonin/tryptophan) showed no robust ASD–control differences; N-acetyl-tryptophan was nominally higher in ASD but did not survive multiple-testing correction. In the ASD subgroup with available Childhood Autism Rating Scale (CARS) data (n = 34), SCFA and tryptophan indices showed only weak, non-significant correlations with global ASD severity. In contrast, correlation analyses revealed two coherent metabolic modules, i.e., an SCFA block with very strong internal correlations among individual SCFAs and total SCFAs and a tryptophan block with strong correlations between metabolites and their normalized ratios, while cross-module correlations were modest. These results indicate that stool SCFA and microbiota-derived tryptophan profiles do not robustly distinguish ASD from controls in this cohort, but they form stable metabolic modules compatible with microbiome–epigenome frameworks. Full article
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