Keywords

Parkinson’s Disease, microbiome dysbiosis, trimethylamine N-oxide, trimethylamine, microbial metabolite, hormesis, glymphatic system

Abstract

This review synthesizes recent literature examining trimethylamine N-oxide (TMAO) synthesis and its potential role in Parkinson’s Disease (PD) pathology. An increase in TMAO plasma and CSF concentration is associated with PD progression and severity. TMAO biosynthesis is a two-step process. First, precursors including carnitine and choline are converted to trimethylamine (TMA) by gut microbes. Second, TMAO is oxidized to TMAO in the liver. Once absorbed into circulation TMAO crosses the blood brain barrier and may influence PD disease pathology by increasing neuroinflammation and astrocyte activation and damaging the cerebral lymphatic system. These mechanisms may contribute to the cognitive and motor symptoms of PD, though further work with PD specific animal models is needed to clarify any causal relationship. Some potentially contradictory evidence suggests that low levels of TMAO may be neuroprotective, maintaining the blood-brain barrier (BBB) and reducing harmful responses to infection. The positive and negative and negative observations regarding TMAO in neurological health could be reconciled through a hormesis hypothesis, where some level of TMAO is helpful , but too much is harmful or aggravates PD symptoms. Future experiments that seek to clarify these questions should standardize TMAO dosage and use ranges that match the TMAO concentration reported in healthy individuals and in PwPD (see table 1).

Document Type

Class Project or Paper

Publication Date

2026-05-30

Language

English

College

Life Sciences

Department

Physiology and Developmental Biology

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