关键词: Cardiometabolic disease Diabetes Diet Gut microbiota Metabolic syndrome Obesity Trimethylamine-N-oxide

来  源:   DOI:10.1186/s13098-024-01368-y   PDF(Pubmed)

Abstract:
BACKGROUND: Elevations in the gut metabolite trimethylamine-N-oxide (TMAO) have been linked to cardiovascular and metabolic diseases. Whether elevated TMAO levels reflect early mechanistic involvement or a sequela of evolving disease awaits elucidation. The purpose of this study was to further explore these potential associations.
METHODS: We investigated relationships between circulating levels of TMAO and its pre-cursor substrates, dietary factors, gut microbiome profiles and disease risk in individuals with a Healthy BMI (18.5 < BMI < 25, n = 41) or key precursor states for cardiometabolic disease: Overweight (25 < BMI < 30 kg/m2, n = 33), Obese (BMI > 30, n = 27) and Metabolic Syndrome (MetS; ≥ 3 ATPIII report criteria, n = 39).
RESULTS: Unexpectedly, plasma [TMAO] did not vary substantially between groups (means of 3-4 µM; p > 0.05), although carnitine was elevated in participants with MetS. Gut microbial diversity and Firmicutes were also significantly reduced in the MetS group (p < 0.05). Exploratory analysis across diverse parameters reveals significant correlations between circulating [TMAO] and seafood intake (p = 0.007), gut microbial diversity (p = 0.017-0.048), and plasma [trimethylamine] (TMA; p = 0.001). No associations were evident with anthropometric parameters or cardiometabolic disease risk. Most variance in [TMAO] within and between groups remained unexplained.
CONCLUSIONS: Data indicate that circulating [TMAO] may be significantly linked to seafood intake, levels of TMA substrate and gut microbial diversity across healthy and early disease phenotypes. However, mean concentrations remain < 5 µM, with little evidence of links between TMAO and cardiometabolic disease risk. These observations suggest circulating TMAO may not participate mechanistically in cardiometabolic disease development, with later elevations likely a detrimental sequela of extant disease.
摘要:
背景:肠道代谢产物三甲胺-N-氧化物(TMAO)的升高与心血管和代谢疾病有关。TMAO水平升高是否反映了早期的机械参与或不断发展的疾病的后遗症,尚待阐明。这项研究的目的是进一步探索这些潜在的关联。
方法:我们研究了TMAO的循环水平与其前体底物之间的关系,饮食因素,健康BMI(18.530,n=27)和代谢综合征(MetS;≥3ATPIII报告标准,n=39)。
结果:出乎意料的是,血浆[TMAO]在组间没有实质性变化(平均值为3-4μM;p>0.05),尽管肉碱在MetS参与者中升高。MetS组肠道微生物多样性和Firmicutes也显著降低(p<0.05)。对不同参数的探索性分析揭示了循环[TMAO]和海鲜摄入量之间的显着相关性(p=0.007),肠道微生物多样性(p=0.017-0.048),和血浆[三甲胺](TMA;p=0.001)。与人体测量参数或心脏代谢疾病风险无明显关联。组内和组间[TMAO]的大多数差异仍无法解释。
结论:数据表明循环[TMAO]可能与海鲜摄入量显著相关,健康和早期疾病表型的TMA底物水平和肠道微生物多样性。然而,平均浓度保持<5µM,几乎没有证据表明TMAO和心脏代谢疾病风险之间存在联系。这些观察结果表明,循环TMAO可能不会在机制上参与心脏代谢疾病的发展。后来的升高可能是现存疾病的有害后遗症。
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