Evidence map›Paper›PMID 41260988›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2026

Butyrate modifies epigenetic and immune pathways in peripheral mononuclear cells from children with neurodevelopmental disorders associated with chromatin dysregulation.

Jessica P Hayes, Velda X Han, Brooke A Keating, Hiroya Nishida, Erica Tsang, Xianzhong Lau, Ruwani Dissanayake, Nader Aryamanesh, Wendy Gold, Melanie Wong and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Medicinal cannabis plant extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in paediatric acute-onset neuropsychiatric syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Trial
  2. Article
  3. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Jessica P HayesKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Velda X HanKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Brooke A KeatingKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Hiroya NishidaKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Erica TsangKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Xianzhong LauAustralian Genome Research Facility Ltd, Melbourne, VIC, Australia.
Ruwani DissanayakeAustralian Genome Research Facility Ltd, Westmead, NSW, Australia.
Nader AryamaneshBioinformatics Group, Children's Medical Research Institute, University of Sydney, Westmead, NSW, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Wendy GoldKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Melanie WongThe Children's Hospital at Westmead, Department of Allergy and Immunology, Australia.
Carolyn EllawayThe Children's Hospital at Westmead, Genetic Metabolic Disorders Service, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Brian S GlossWestmead Research Hub, Westmead Institute for Medical Research, Westmead, NSW, Australia.
Shekeeb S MohammadKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Markus J HoferSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Peter ValtchevSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia; School of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW, Australia.
Shrujna PatelKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; The University of Sydney, School of Medical Sciences and Discipline of Child and Adolescent Health, Faculty of Medicine and Health, Sydney, NSW, Australia.
Russell C DaleKids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; The University of Sydney, School of Medical Sciences and Discipline of Child and Adolescent Health, Faculty of Medicine and Health, Sydney, NSW, Australia. Electronic address: russell.dale@sydney.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pathogenic DNA variants in chromatin-related genes constitute an important minority of neurodevelopmental disorders (NDDs). Epigenetic mechanisms, including chromatin regulation driven by genetic or environmental factors, are increasingly recognised as key contributors to pathogenesis of diverse NDDs. We hypothesise that therapeutic strategies targeting chromatin dysregulation, such as histone deacetylase inhibition with butyrate, may be a potential disease modifying therapy for NDDs. We first performed peripheral blood bulk RNA sequencing (RNA-seq) to explore baseline gene regulation in children with chromatin-related NDDs (Kabuki syndrome (KMT2D, n ​= ​4), CHARGE syndrome (CHD7, n ​= ​2), and Rett syndrome (MECP2, n ​= ​5), and children with NDDs but without a monogenic diagnosis (non-monogenic, n ​= ​8), compared with sex-matched healthy controls (total n ​= ​21). Next, to explore the effects of butyrate, single-cell RNA sequencing (scRNA-seq) was performed on 101,539 peripheral immune cells from four selected patients (one per condition) and two controls, before and after butyrate treatment. At baseline, dysregulation of ribosomal and immune pathways was seen in all four NDD cohorts (KMT2D, CHD7, MECP2, non-monogenic) compared to controls. Butyrate largely reversed these pathways, normalising ribosomal and immune pathways in patient and control cells. Butyrate induced up-regulation of ribosome, GTPase, cytoskeletal, mitochondrial pathways, and down-regulation of epigenetic and immune pathways. In conclusion, we identified a common ribosomal-immune RNA signature in chromatin-related NDDs, and a similar signature in non-monogenic NDDs. We showed that butyrate modulates epigenetic and immune gene networks in monogenic and non-monogenic NDDs, positioning butyrate as a promising therapeutic modulator across diverse NDDs.

Indexed as

ButyratesChromatinEpigenesis, GeneticLeukocytes, MononuclearNeurodevelopmental DisordersAdolescentChildChild, PreschoolFemaleHumansMaleButyratesChromatinButyrateChromatinEpigeneticsHistone deacetylase inhibitionNeurodevelopmental disordersNeuroregression

Identifiers

PMID41260988
PMCPMC12976508

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.