Impact of long-term high dietary fat intake and regular exercise on serum TMAO and microbiome composition in female rats

BACKGROUD: Trimethylamine oxide (TMAO) represents a gut metabolite and it's physiological concentration is proposed to be influenced by the abundance of precursor trimethylamine (TMA)-producing microbiota in the gut. OBJECTIVE: Lifestyle factors, such as diet and exercise, modify the microbiome, but their long-term impact on plasma TMAO and TMA production in the gut is poorly understood. METHODS: Fecal microbiome composition was analyzed and correlated with TMAO serum concentrations in female Sprague-Dawley rats that received either a healthy normal or a high-fat diet (HFD) for 10 months. Half of the animals performed regular running exercise, the other half served as sedentary controls. RESULTS: HFD consumption induced an alteration of the fecal microbiome with increased alpha diversity on ASV levels. More importantly, HFD reduced the abundance of genera containing potential TMA producers, such as certain members of Clostridia and Lachnospiraceae. In line with this observation, serum TMAO concentrations were found to be lower with HFD and to correlate with the abundance of these genera. Regular exercise also induced changes in microbiome beta diversity but had no effect on serum TMAO in female rats. CONCLUSION: A diet containing high amounts of dietary fat reduced serum TMAO, probably through a reduced intestinal abundance of TMA-producing bacteria. In contrast, regular exercise altered beta diversity of the microbiome composition, but without significant effects on serum TMAO concentrations.