ArticleeLife2022
Chemogenetics defines a short-chain fatty acid receptor gut-brain axis.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
23 citing papers in PubMed, 39 citations in OpenAlex.
- The Emerging Short Chain Fatty Acid Enriched Metabotype in Irritable Bowel Syndrome and Its Potential Clinical Relevance.Alimentary pharmacology & therapeutics · 2026Trial
- Short-chain fatty acid-producing commensals: Key modulators of AD neuroinflammation via the microbiota-gut-brain axis.Current research in microbial sciences · 2026Review
- Prenatal cigarette exposure induces offspring hyperactivity and affective alterations via gut -brain axis metabolic dysregulation and region-specific neuronal hyperactivation.Brain, behavior, & immunity - health · 2026Article
- Advances in the mechanism of low FODMAP diet in the treatment of irritable bowel syndrome: a review.Frontiers in nutrition · 2026Review
- Microbiota-neuroepithelial signalling across the gut-brain axis.Nature reviews. Microbiology · 2025Review
- Interaction of the Vagus Nerve and Serotonin in the Gut-Brain Axis.International journal of molecular sciences · 2025Review
- The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms.Journal of neuroinflammation · 2025Review
- Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy.Microbial biotechnology · 2025Review
- Microbiome-driven IBS metabotypes influence response to the low FODMAP diet: insights from the faecal volatome.EBioMedicine · 2024Article
- Host-microbe interactions: communication in the microbiota-gut-brain axis.Current opinion in microbiology · 2024Review
- Review
- Gut microbiome affects the response to immunotherapy in non-small cell lung cancer.Thoracic cancer · 2024Article
- Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions.Aging and disease · 2024Review
- Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.eLife · 2023Article
- Breast cancers as ecosystems: a metabolic perspective.Cellular and molecular life sciences : CMLS · 2023Review
- Discovery of Potent Tetrazole Free Fatty Acid Receptor 2 Antagonists.Journal of medicinal chemistry · 2023Article
- Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections.Open biology · 2023Review
- Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management.Nature reviews. Rheumatology · 2023Review
- Communication of gut microbiota and brainFrontiers in microbiology · 2023Review
- GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis.Frontiers in endocrinology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Volatile small molecules, including the short-chain fatty acids (SCFAs), acetate and propionate, released by the gut microbiota from the catabolism of nondigestible starches, can act in a hormone-like fashion via specific G-protein-coupled receptors (GPCRs). The primary GPCR targets for these SCFAs are FFA2 and FFA3. Using transgenic mice in which FFA2 was replaced by an altered form called a Designer Receptor Exclusively Activated by Designer Drugs (FFA2-DREADD), but in which FFA3 is unaltered, and a newly identified FFA2-DREADD agonist 4-methoxy-3-methyl-benzoic acid (MOMBA), we demonstrate how specific functions of FFA2 and FFA3 define a SCFA-gut-brain axis. Activation of both FFA2/3 in the lumen of the gut stimulates spinal cord activity and activation of gut FFA3 directly regulates sensory afferent neuronal firing. Moreover, we demonstrate that FFA2 and FFA3 are both functionally expressed in dorsal root- and nodose ganglia where they signal through different G proteins and mechanisms to regulate cellular calcium levels. We conclude that FFA2 and FFA3, acting at distinct levels, provide an axis by which SCFAs originating from the gut microbiota can regulate central activity.
Indexed as
Identifiers
What OpenQuestion holds
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.