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High-Fat Diet with Normal Caloric Intake Elevates TMA and TMAO Production and Reduces Microbial Diversity in Rats
Mateusz Szudzik1, Mikołaj Zajdel1, Emilia Samborowska2
1Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, 02-091 Warsaw, Poland.
Nutrients
|July 12, 2025
Summary
A high-fat diet, even with controlled calories, significantly increases trimethylamine (TMA) and trimethylamine N-oxide (TMAO) levels while reducing gut microbial diversity in rats.
Area of Science:
- Microbiology
- Metabolomics
- Nutritional Science
Background:
- Gut microbiota produces trimethylamine (TMA) and trimethylamine N-oxide (TMAO), linked to cardiometabolic diseases.
- The impact of high-fat diets (HFDs) and high-disaccharide diets (HDDs) on TMA/TMAO production under physiological caloric intake is not well understood.
Purpose of the Study:
- To investigate the effects of HFDs and HDDs on gut microbiota composition and TMA/TMAO production in rats at physiological caloric intake.
- To determine how diet composition, independent of caloric excess, influences gut microbiota and cardiometabolic biomarkers.
Main Methods:
- Rats were fed a standard diet, HFD, or HDD for 12 weeks, with caloric intake controlled.
- Gut bacterial diversity was assessed using 16S rRNA gene sequencing.
- Urinary and plasma metabolites (TMA, TMAO) were quantified using HPLC-MS.
Main Results:
- The HFD group exhibited significantly higher urinary TMA and TMAO levels compared to control and HDD groups.
- HFD led to a marked reduction in gut bacterial diversity, including species richness and phylogenetic diversity.
- Specific bacterial taxa (Pasteurellaceae, S24-7) were positively correlated with TMAO levels.
- The HDD group showed increased microbial diversity compared to control and HFD groups.
Conclusions:
- Dietary fat content, not just caloric load, significantly impacts TMA/TMAO production.
- High-fat diets can negatively alter gut microbiota composition and increase cardiometabolic risk factors.
- Understanding diet-microbiota interactions is crucial for managing cardiometabolic health.

