{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306671/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306671"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Fasting primes small intestinal regeneration after damage via a microbiome-metabolite-chromatin axis","description":"Fasting protects the small intestine epithelial cells from high-dose radiation injury, yet the mechanisms linking fasting to epithelial regeneration remain incompletely understood. Akkermansia muciniphila (AKK) is both necessary and sufficient for fasting-induced radioprotection. Selective depletion of AKK abolishes fasting-mediated preservation of SI stem cells, while recolonization restores epithelial integrity and survival. AKK produces the short-chain fatty acid propionate, which, together with host-derived β-hydroxybutyrate (β-OHB), induces histone H3 acetylation (H3K27ac, H3K9ac) and β-hydroxybutyrylation (H3K9bhb) in crypt epithelial cells, remodeling enhancer–promoter landscapes. CUT&Tag and single-cell ATAC-seq analyses show that fasting, in an AKK-dependent manner, expands a Clu⁺Olfm4⁺ “revival” stem cell (persister cells) population enriched for HNF, FOXA, GATA and KLF transcription factor motifs, establishing a pro-regenerative chromatin state that persists through injury-repair phases. CTCF and BORIS activities persist, suggesting a role in maintaining epigenetic memory for intestinal regeneration after radiation. This microbiota–metabolite–chromatin axis primes persister cells for rapid regeneration after damage and offers a strategy to protect normal tissues during radiation therapy.","dates":{"publication":"2026/06/08"},"accession":"GSE306671","cross_references":{"GSM":["GSM9205749","GSM9205748","GSM9205750","GSM9205751"],"GPL":["24247"],"GSE":["306671"],"taxon":["Mus musculus"]}}