ArticleMicrobiome2021
Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.
Article in Microbiome, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 3 of them syntheses 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
133 citing papers in PubMed, 3 syntheses or guidelines pooled it, 204 citations in OpenAlex.
- Pooled it
- Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Gut microbes in cerebrovascular diseases: Gut flora imbalance, potential impact mechanisms and promising treatment strategies.Frontiers in immunology · 2022Pooled it
- Article
- Review
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Modulating the Gut-Microbiota-Brain Axis in Alzheimer's Disease: Therapeutic Potential of Nutritional and Metabolic Factors.CNS neuroscience & therapeutics · 2026Review
- Maternal and infant gut microbiome.iMeta · 2026Review
- Trimethylamine N-oxide in exercise physiology: a gut microbiota-derived signal linking metabolic stress, redox balance and cardiometabolic health.European journal of applied physiology · 2026Review
- Bidirectional communication between the gut microbiota and the central nervous system.Neural regeneration research · 2026Article
- Gut Microbiota and Ischemic Stroke: From Pre-Stroke Dysbiosis and Acute-Phase Changes to Therapeutic Applications.Brain and behavior · 2026Review
- Intergenerational effects of the microbiota on neurodevelopment: mechanisms and therapeutic perspectives.Acta pharmacologica Sinica · 2026Review
- Is Ergothioneine an Important Source of Plasma TrimethylamineAntioxidants (Basel, Switzerland) · 2026Article
- Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case-control study.IBRO neuroscience reports · 2026Article
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Pathogenesis and therapeutic strategies for neuropsychiatric lupus centered on innate immune activation.Human cell · 2026Review
- Plasma acetic acid mediates the relationship between gut microbiome and various health measures in older adults.Communications medicine · 2026Article
- MEKK3 bridges gut-brain communication and cerebral cavernous malformation pathogenesis.Cell death discovery · 2026Review
- Microbial-Immune Interplay in CNS Autoimmune Diseases: Lessons from Animal Models and Clinical Studies.European journal of immunology · 2026Review
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundCommunication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied.
resultsHere, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner.
conclusionOur findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract.
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.