ArticleScientific reports2016
Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 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 Probiotic Supplementation on Circadian Rhythm-Related Gene Expression and Body Weight in Mice With Disturbed Circadian Rhythms.Molecular nutrition & food research · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Grape Seed Proanthocyanidins Enhance Time-Dependent HO-1 Activation and Improve Redox Homeostasis in Obesity-Induced Hepatic Dysfunction.Antioxidants (Basel, Switzerland) · 2026Article
- Timekeepers of the gut: host circadian rhythms and microbial modulators.Life metabolism · 2026Review
- New insights into the skeletal muscle circadian clock in ruminants.Journal of animal science and biotechnology · 2026Review
- Reciprocal oscillation and host-microbial communication in liver metabolic control.Gut microbes · 2025Review
- Bidirectional interactions between circadian rhythms and the gut microbiome.Applied microbiology and biotechnology · 2025Review
- Autophagy and the peroxisome proliferator-activated receptor signaling pathway: A molecular ballet in lipid metabolism and homeostasis.Molecular and cellular biochemistry · 2025Review
- I "Gut" Rhythm: the microbiota as a modulator of the stress response and circadian rhythms.The FEBS journal · 2025Review
- The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research.Nature metabolism · 2025Review
- An overview of basic pathophysiological interactions between gut bacteria and their host.Frontiers in nutrition · 2025Review
- Liver as a nexus of daily metabolic cross talk.International review of cell and molecular biology · 2025Review
- Circadian de(regulation) in physiology: implications for disease and treatment.Genes & development · 2024Review
- Interaction Between Early Meals (Big-Breakfast Diet), Clock Gene mRNA Expression, and Gut Microbiome to Regulate Weight Loss and Glucose Metabolism in Obesity and Type 2 Diabetes.International journal of molecular sciences · 2024Review
- PPARs as Key Transcription Regulators at the Crossroads of Metabolism and Inflammation.International journal of molecular sciences · 2024Article
- The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway.Cells · 2024Article
- Sex-dependent circadian alterations of both central and peripheral clock genes expression and gut-microbiota composition during activity-based anorexia in mice.Biology of sex differences · 2024Article
- Circadian regulation of liver function: from molecular mechanisms to disease pathophysiology.Nature reviews. Gastroenterology & hepatology · 2023Review
- Gut microbes and the liver circadian clock partition glucose and lipid metabolism.The Journal of clinical investigation · 2023Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum: Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.2016 · Maha, Al-Asmakh [corrected to Al-Asmakh, Maha]
Authors and funding
19 authors at 8 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function.
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Registered trials
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.