In vitro butyrate modifies epigenetic and immune pathways in peripheral mononuclear cells from children with neurodevelopmental disorders associated with chromatin dysregulation

Patient cells also underwent scRNA seq sequencing after in vitro butyrate treatment. Untreated patient cells showed dysregulation of ribosomal and immune pathways compared to controls. Specifically, KMT2D, CHD7, and the non-monogenic patients exhibited downregulation of ribosomal pathways, and upregulation of immune pathways.

In contrast, the MECP2 patient displayed upregulation of ribosomal pathways and mixed regulation of immune pathways. Butyrate treatment largely reversed these pathways, normalizing ribosomal and immune pathways in KMT2D, CHD7, and non-monogenic patient cells, with partial effects in MECP2. Overall, butyrate induced up-regulation of ribosome, GTPase, cytoskeletal, mitochondrial pathways, and down-regulation of epigenetic (histone, transcription factors) and immune pathways.

We propose that chromatin dysregulation is associated with a common RNA signature involving ribosomal pathways and immune dysregulation. Butyrate is a potential modulator of epigenetic and immune dysregulation in NDDs associated with chromatin dysregulation.