Szudzik Mateusz, Zajdel Mikołaj, Samborowska Emilia, Perlejewski Karol, Radkowski Marek, Ufnal Marcin
Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, 02-091 Warsaw, Poland.
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Nutrients. 2025 Jul 5;17(13):2230. doi: 10.3390/nu17132230.
Trimethylamine (TMA), produced by gut microbiota, and its derivative trimethylamine N-oxide (TMAO) are both associated with cardiometabolic diseases. While the effects of high-fat diets (HFDs) and high-disaccharide diets (HDDs) on gut microbiota in the context of obesity have been well studied, their impact on TMA/TMAO production, particularly alongside physiological caloric intake, remains obscure. This study investigates how standard HFDs and HDDs alongside physiological caloric intake influence gut microbiota composition and TMA/TMAO production in rats. Sprague Dawley rats were fed one of three diets a standard diet, an HFD, or an HDD for 12 weeks, with chow availability adjusted by age to maintain physiological caloric intake. Gut bacterial diversity was analyzed using 16S rRNA gene sequencing, and metabolites were quantified via High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) in urine and plasma. The HFD group had significantly higher urinary levels of TMA and TMAO compared to the control and HDD groups. Gut bacterial diversity in the HFD group was markedly reduced, displaying the lowest species richness and phylogenetic diversity among all the groups. Notably, Pasteurellaceae (within the order Pasteurellales) and S24-7 (within the order Bacteroidales) were positively correlated with TMAO levels. The demonstrated HDD group increased microbial diversity compared to both the control and HFD groups. A high-fat diet during controlled and physiological caloric intake increases TMA/TMAO production and reduces gut microbial diversity. This underscores the role of diet composition, beyond caloric excess, in shaping gut microbiota and the related cardiometabolic biomarkers.
由肠道微生物群产生的三甲胺（TMA）及其衍生物氧化三甲胺（TMAO）均与心脏代谢疾病有关。虽然高脂肪饮食（HFDs）和高双糖饮食（HDDs）对肥胖背景下肠道微生物群的影响已得到充分研究，但它们对TMA/TMAO产生的影响，尤其是在生理热量摄入的情况下，仍不清楚。本研究调查了标准HFDs和HDDs以及生理热量摄入如何影响大鼠的肠道微生物群组成和TMA/TMAO产生。将Sprague Dawley大鼠喂食三种饮食之一：标准饮食、HFD或HDD，持续12周，并根据年龄调整食物供应量以维持生理热量摄入。使用16S rRNA基因测序分析肠道细菌多样性，并通过高效液相色谱-质谱联用（HPLC-MS）对尿液和血浆中的代谢物进行定量。与对照组和HDD组相比，HFD组的尿液中TMA和TMAO水平显著更高。HFD组的肠道细菌多样性明显降低，在所有组中显示出最低的物种丰富度和系统发育多样性。值得注意的是，巴斯德氏菌科（巴斯德氏菌目内）和S24-7（拟杆菌目内）与TMAO水平呈正相关。与对照组和HFD组相比，HDD组的微生物多样性增加。在控制和生理热量摄入期间，高脂肪饮食会增加TMA/TMAO的产生并降低肠道微生物多样性。这突出了饮食组成在塑造肠道微生物群和相关心脏代谢生物标志物方面的作用，而不仅仅是热量过剩的影响。
