ArticleCellular and molecular gastroenterology and hepatology2022
Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- Environmental Microbial Cues Alter Embryonic Development and Stress Responses in Vertebrates: Insights From the Zebrafish (Danio rerio) Model.Molecular ecology · 2025Article
- Dysregulated Intestinal Nutrient Absorption in Obesity Is Associated with Altered Chromatin Accessibility.Organoids · 2025Article
- Early subclinical stages of the inflammatory bowel diseases: insights from human and animal studies.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.Brain, behavior, and immunity · 2024Article
- Transcriptional regulation of metabolism in the intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia.Human genetics · 2023Article
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.Genetics · 2022Article
- Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe intestine constantly interprets and adapts to complex combinations of dietary and microbial stimuli. However, the transcriptional strategies by which the intestinal epithelium integrates these coincident sources of information remain unresolved. We recently found that microbiota colonization suppresses epithelial activity of hepatocyte nuclear factor 4 nuclear receptor transcription factors, but their integrative regulation was unknown.
methodsWe compared adult mice reared germ-free or conventionalized with a microbiota either fed normally or after a single high-fat meal. Preparations of unsorted jejunal intestinal epithelial cells were queried using lipidomics and genome-wide assays for RNA sequencing and ChIP sequencing for the activating histone mark H3K27ac and hepatocyte nuclear factor 4 alpha.
resultsAnalysis of lipid classes, genes, and regulatory regions identified distinct nutritional and microbial responses but also simultaneous influence of both stimuli. H3K27ac sites preferentially increased by high-fat meal in the presence of microbes neighbor lipid anabolism and proliferation genes, were previously identified intestinal stem cell regulatory regions, and were not hepatocyte nuclear factor 4 alpha targets. In contrast, H3K27ac sites preferentially increased by high-fat meal in the absence of microbes neighbor targets of the energy homeostasis regulator peroxisome proliferator activated receptor alpha, neighbored fatty acid oxidation genes, were previously identified enterocyte regulatory regions, and were hepatocyte factor 4 alpha bound.
conclusionsHepatocyte factor 4 alpha supports a differentiated enterocyte and fatty acid oxidation program in germ-free mice, and that suppression of hepatocyte factor 4 alpha by the combination of microbes and high-fat meal may result in preferential activation of intestinal epithelial cell proliferation programs. This identifies potential transcriptional mechanisms for intestinal adaptation to multiple signals and how microbiota may modulate intestinal lipid absorption, epithelial cell renewal, and systemic energy balance.
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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 Socratic graph.