ArticleGastroenterology2022
Histone Deacetylase Inhibition by Gut Microbe-Generated Short-Chain Fatty Acids Entrains Intestinal Epithelial Circadian Rhythms.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- The modulatory role of short-chain fatty acids on peripheral circadian gene expression: a systematic review.Frontiers in physiology · 2025Pooled it
- Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial.Lipids in health and disease · 2024Trial
- Gut microbiota-regulated glutathione metabolic rhythms restore obesity-induced colonic inflammatory oscillations.Gut microbes · 2026Article
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- Gut dysbiosis‑derived butyrate loss predicts feeding intolerance: Multiomics evidence guiding nurse‑driven microbiota‑supportive interventions (Review).Molecular medicine reports · 2026Review
- Curcumin Pretreatment Alleviates Early Mannheimia Haemolytica-Induced Pulmonary Injury in Mice and Is Associated with Changes in Gut Microbial Composition.Microorganisms · 2026Article
- The impact of microbial metabolites on host chromatin and epigenetic regulation.Nature metabolism · 2026Review
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- Functional effects of rosmarinic acid on gut health and epigenetic regulation in antibiotic-free poultry diets.Poultry science · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Phytochemicals remodel antitumor immunity via the "microbiota-metabolite-receptor" axis: focus on colorectal cancer and immunotherapy.Medical oncology (Northwood, London, England) · 2026Review
- Experimental models for intestinal host-microbe interactions.EMBO molecular medicine · 2026Review
- The importance of meal timing for maintenance of daily rhythms in the gut transcriptome and microbiota.Npj biological timing and sleep · 2026Article
- Letter to the Editor: Circadian and microbial misalignment in metabolic dysfunction-associated steatotic liver disease - mechanistic insights and chronotherapeutic potential.World journal of experimental medicine · 2026Article
- Gut Lactate Boosts Ruminococcus via Histone Lactylation to Mediate Time-Restricted Feeding Protection in Crohn's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circadian Regulation of Gut Microbial Metabolites in Intestinal Epithelial Homeostasis.Metabolites · 2026Review
- Microbiota-Derived Metabolites in Developmental Programming: Bridging Early-Life Gut Microbiota to Childhood Metabolic Disorders.Current medical science · 2026Review
- Gut Microbiome-Sleep Crosstalk: Mechanistic Pathways, Dysbiosis Signatures, and Microbiome-Based Interventions.Brain and behavior · 2026Review
- Gut Microbiota, Metabolic Markers, and Systemic Inflammation in Young Women with Self-Reported Rosacea: An Exploratory Cross-Sectional Study.Journal of clinical medicine · 2026Article
- Lactobacillus-derived indole-3-lactic acid suppresses meningioma malignant phenotypes by direct anti-proliferative effects and macrophage reprogramming.Journal of translational medicine · 2026Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe circadian clock orchestrates ∼24-hour oscillations of gastrointestinal epithelial structure and function that drive diurnal rhythms in gut microbiota. Here, we use experimental and computational approaches in intestinal organoids to reveal reciprocal effects of gut microbial metabolites on epithelial timekeeping by an epigenetic mechanism.
methodsWe cultured enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota. Circadian oscillations of bioluminescent PER2 and Bmal1 were measured in the presence or absence of individual ASF supernatants. Separately, we applied machine learning to ASF metabolomics to identify phase-shifting metabolites.
resultsSterile filtrates from 3 of 7 ASF species (ASF360 Lactobacillus intestinalis, ASF361 Ligilactobacillus murinus, and ASF502 Clostridium species) induced minimal alterations in circadian rhythms, whereas filtrates from 4 ASF species (ASF356 Clostridium species, ASF492 Eubacterium plexicaudatum, ASF500 Pseudoflavonifactor species, and ASF519 Parabacteroides goldsteinii) induced profound, concentration-dependent phase shifts. Random forest classification identified short-chain fatty acid (SCFA) (butyrate, propionate, acetate, and isovalerate) production as a discriminating feature of ASF "shifters." Experiments with SCFAs confirmed machine learning predictions, with a median phase shift of 6.2 hours in murine enteroids. Pharmacologic or botanical histone deacetylase (HDAC) inhibitors yielded similar findings. Further, mithramycin A, an inhibitor of HDAC inhibition, reduced SCFA-induced phase shifts by 20% (P < .05) and conditional knockout of HDAC3 in enteroids abrogated butyrate effects on Per2 expression. Key findings were reproducible in human Bmal1-luciferase enteroids, colonoids, and Per2-luciferase Caco-2 cells.
conclusionsGut microbe-generated SCFAs entrain intestinal epithelial circadian rhythms by an HDACi-dependent mechanism, with critical implications for understanding microbial and circadian network regulation of intestinal epithelial homeostasis.
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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.