This molecule links your diet to stroke and Alzheimer's disease.

This molecule links your diet to stroke and Alzheimer's disease.

Red meat and eggs feed gut bacteria that make Tmao - a molecule now linked to stroke, Alzheimer's and heart failure. This new review shows how diet, probiotics and even statins could help stop them in their tracks.

What you feed your gut microbiota can influence your risk of heart disease and neurodegeneration. Recent research has highlighted the role of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite, as a key biomarker of health, metabolism and disease.

Published in a recent review in the JournalMetabolitesA team of scientists in Italy studied the role of diet and gut bacteria in the biosynthesis of TMAO, as well as the effects of this metabolite on the risk of neurodegenerative and cardiovascular diseases.

Gut microbiome metabolites

The human gut microbiota plays a crucial role in processing dietary components, particularly through the production of metabolites that influence health. One such compound, Tmao, forms when gut bacteria break down choline and carnitine, which are found in red meat, eggs and dairy products. These are converted into trimethylamine (TMA), which is then oxidized by the liver enzyme flavin-containing monooxygenase 3 (FMO3) to produce TMAO.

Genetic variation in FMO3 as well as differences in sex hormones and liver function may influence how efficiently TMA is converted to TMAO, thereby influencing individual susceptibility to disease.

TMAO was initially recognized for its osmoprotective role in marine organisms and has received attention due to its strong correlation with cardiovascular disease, atherosclerosis, peripheral artery disease, hypertension, and neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.

Elevated TMAO levels have been linked to increased platelet aggregation, endothelial dysfunction and systemic inflammation - mechanisms that contribute to heart disease and stroke. TMAO also increases intracellular calcium release in platelets, improving their reactivity and promoting thrombus formation.

Furthermore, TMAO promotes oxidative stress and inflammation by activating the NLRP3 inflammasome and impairing the SIRT3-SOD2 mitochondrial defense pathway, contributing to both vascular damage and neuroinflammation.

Schematic representation of TMAO biosynthesis and metabolism.

The current study

The review aimed to bridge knowledge gaps by assessing how dietary components, microbiota composition and potential therapies influence TMAO levels and disease risk.

The researchers analyzed how specific gut bacteria metabolize dietary choline, carnitine, betaine and other precursors into TMA, which is then converted into TMAO in the liver. They also evaluated results from experimental models, clinical trials and epidemiological studies to clarify the involvement of TMAO in disease.

Dietary patterns were examined by comparing TMAO levels in individuals consuming red meat diets with those following plant-based or Mediterranean diets. The team also investigated probiotic interventions, nutraceuticals and even pharmaceutical agents that can modulate TMAO synthesis or metabolism.

Key insights

TMAO levels are strongly shaped by both diet and gut microbiota composition. Red meat, eggs, and dairy intake increase TMAO levels, while plant-based or Mediterranean diets—in fiber and polyphenols—are associated with lower levels.

TMAO contributes to cardiovascular disease by impairing nitric oxide production, disrupting lipid and cholesterol metabolism, promoting foam cell formation, and increasing platelet hyperreactivity. It also impairs endothelial progenitor cell function and alters pathways critical for neovascularization and vascular repair.

Beyond heart disease, the review links TMAO to cognitive decline, blood-brain barrier dysfunction, and beta-amyloid and tau aggregation hallmarks of Alzheimer's disease. It is also involved in Parkinson's disease through mitochondrial dysfunction and chronic inflammation.

Elevated TMAO was associated with poor outcomes in heart failure, increased mortality in peripheral artery disease, and increased risk of stroke and hypertension.

Schematic representation of TMAO transport in endothelial cells via the endothelial TMAO transporter (ETT) and its clinical implications.

Therapeutic and lifestyle interventions

Interventions that reduce TMAO include:

• Ernährungsveränderungen wie das Reduzieren von rotem Fleisch und das Erhöhen von Ballaststoffen/Polyphenolen.
• Probiotika, insbesondere bestimmte Stämme von Lactobacillus Und Bifidobacteriumdie die Mikrobiota modulieren, um die TMA -Produktion zu reduzieren. Allerdings sind nicht alle Probiotika wirksam – Formulationen wie VSL#3 haben keinen Einfluss auf die TMAO -Spiegel in Versuchen gezeigt.
• Nutraceuticals, einschließlich Resveratrol, Quercetin und der polyphenolreichen Ergänzung Taurisolo®, haben vielversprechende Ergebnisse zur Verringerung der TMAO und zur Schutz der Gefäßgesundheit gezeigt.

The review also highlighted the potential role of pharmaceuticals:

• Statine können TMAO durch modulierende Darmmikrobiota und Gallensäurestoffwechsel senken.
• ACE -Inhibitoren und Schleifendiuretika beeinflussen indirekt die TMAO -Clearance oder -Synthese durch Auswirkungen auf die Nierenausscheidung und die Darmflora.
• Die Überwachung von TMAO kann die kardiovaskuläre Risikostratifizierung verbessern, insbesondere bei Patienten mit Komorbiditäten.

Despite these advances, the review acknowledged several limitations, including inconsistent probiotic results, variations in individual microbiomes, and a lack of long-term human studies.

Conclusions

TMAO has emerged as a key metabolite linking diet, gut microbiota, host genetics and disease. The review emphasized that nutritional and probiotic strategies, along with personalized approaches based on microbiome and genetic profiling, could provide powerful tools to mitigate TMAO-associated health risks.

Monitoring TMAO levels may also improve early detection of cardiovascular and neurodegenerative diseases. While research continues, simple changes—such as eating a plant-rich diet, using targeted probiotics, or considering nutraceuticals like Taurisolo®—may provide a preventive benefit in long-term health.

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