Laboratory investigation; a journal of technical methods and pathologyAug 3, 2018

Gut microbe chemical trimethylamine N-oxide linked to heart muscle growth and scarring

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Updated Mar 21, 2026

Abstract

TMAO levels were significantly elevated in rats after 6 weeks of induced cardiac hypertrophy.

TMAO, derived from gut microbes, is associated with increased cardiovascular disease risk.
Induction of cardiac hypertrophy in rats was achieved through transverse aortic constriction (TAC).
TMAO treatment in cultured heart cells stimulated hypertrophy, indicated by larger cell size and increased levels of specific markers.
In rats, TMAO treatment led to both cardiac hypertrophy and fibrosis.
Using antibiotics to reduce TMAO synthesis decreased the cardiac hypertrophy and fibrosis caused by TAC.
Inhibition of Smad3 reduced the effects of TMAO on heart cell size and hypertrophic marker expression.

Simplified

Trimethylamine N-oxide (TMAO), a gut microbe-derived metabolite of dietary choline and other trimethylamine-containing nutrients, has been linked to increased cardiovascular disease risk. It is unknown whether TMAO plays a role in the development of cardiac hypertrophy. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in Sprague-Dawley (SD) rats. We observed that TMAO levels were significantly elevated in SD rats after 6 weeks of TAC, suggesting the potential role of TMAO in regulating cardiac hypertrophy. In cultured cardiomyocytes, TMAO treatment stimulated cardiac hypertrophy, as indicated by increased cell area of cardiomyocytes and expression of hypertrophic markers including atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). Additionally, TMAO treatment induced cardiac hypertrophy and cardiac fibrosis in SD rats. Reducing TMAO synthesis by antibiotics (Abs) attenuated TAC-induced cardiac hypertrophy and fibrosis. Furthermore, pharmacological inhibition of Smad3 by SIS3 significantly reduced the expression of ANP and β-MHC, and cardiomyocyte cell size in TMAO-treated group. These data for the first time demonstrate that gut microbe-derived metabolite TMAO induces cardiac hypertrophy and fibrosis involving Smad3 signaling, suggesting that inhibition of gut microbes or generation of TMAO may become a potential target for the prevention and treatment of cardiac hypertrophy.

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Gut microbe chemical trimethylamine N-oxide linked to heart muscle growth and scarring

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