PDF(Pubmed)
Abstract：
(1) Aims: Gut microbiota metabolites may play integral roles in human metabolism and disease progression. However, evidence for associations between metabolites and cardiometabolic risk factors is sparse, especially in high-risk Hispanic populations. We aimed to evaluate the cross-sectional and longitudinal relationships between gut microbiota related metabolites and measures of glycemia, dyslipidemia, adiposity, and incident type 2 diabetes in two Hispanic observational cohorts. (2) Methods: We included data from 670 participants of the Boston Puerto Rican Health Study (BPRHS) and 999 participants of the San Juan Overweight Adult Longitudinal Study (SOALS). Questionnaires and clinical examinations were conducted over 3 years of follow-up for SOALS and 6 years of follow-up for BPRHS. Plasma metabolites, including L-carnitine, betaine, choline, and trimethylamine N-oxide (TMAO), were measured at baseline in both studies. We used multivariable linear models to evaluate the associations between metabolites and cardiometabolic risk factors and multivariable logistic and Poisson regressions to assess associations with prevalent and incident type 2 diabetes, adjusted for potential confounding factors. Cohort-specific analyses were combined using a fixed-effects meta-analysis. (3) Results: Higher plasma betaine was prospectively associated with lower fasting glucose [-0.97 mg/dL (95% CI: -1.59, -0.34), p = 0.002], lower HbA1c [-0.02% (95% CI: -0.04, -0.01), p = 0.01], lower HOMA-IR [-0.14 (95% CI: -0.23, -0.05), p = 0.003], and lower fasting insulin [-0.27 mcU/mL (95% CI: -0.51, -0.03), p = 0.02]. Betaine was also associated with a 22% lower incidence of type 2 diabetes (IRR: 0.78, 95% CI: 0.65, 0.95). L-carnitine was associated with lower fasting glucose [-0.68 mg/dL (95% CI: -1.29, -0.07), p = 0.03] and lower HbA1c at follow-up [-0.03% (95% CI: -0.05, -0.01), p < 0.001], while TMAO was associated with higher fasting glucose [0.83 mg/dL (95% CI: 0.22, 1.44), p = 0.01] and higher triglycerides [3.52 mg/dL (95% CI: 1.83, 5.20), p < 0.0001]. Neither choline nor TMAO were associated with incident type 2 diabetes. (4) Conclusions: Higher plasma betaine showed consistent associations with a lower risk of glycemia, insulinemia, and type 2 diabetes. However, TMAO, a metabolite of betaine, was associated with higher glucose and lipid concentrations. These observations demonstrate the importance of gut microbiota metabolites for human cardiometabolic health.
摘要：
(1)目的：肠道菌群代谢产物可能在人体代谢和疾病进展中发挥重要作用。然而,代谢物和心脏代谢危险因素之间关联的证据很少，特别是在高危西班牙裔人群中。我们旨在评估肠道微生物群相关代谢产物与血糖测量之间的横截面和纵向关系。血脂异常,肥胖,和2型糖尿病事件在两个西班牙裔观察队列。（2）方法：我们纳入了波士顿波多黎各人健康研究（BPRHS）的670名参与者和圣胡安超重成人纵向研究（SOALS）的999名参与者的数据。在SOALS随访3年和BPRHS随访6年期间进行问卷调查和临床检查。血浆代谢物，包括左旋肉碱,甜菜碱,胆碱，和三甲胺N-氧化物（TMAO），在两项研究中都在基线测量。我们使用多变量线性模型来评估代谢产物与心脏代谢危险因素之间的关联，并使用多变量logistic和Poisson回归来评估与流行和偶发2型糖尿病的关联。针对潜在的混杂因素进行了调整。队列特异性分析使用固定效应荟萃分析进行组合。（3）结果：较高的血浆甜菜碱与较低的空腹血糖[-0.97mg/dL（95％CI：-1.59，-0.34），p=0.002],较低的HbA1c[-0.02%（95%CI：-0.04，-0.01），p=0.01],较低的HOMA-IR[-0.14（95%CI：-0.23，-0.05），p=0.003],和较低的空腹胰岛素[-0.27mcU/mL（95％CI：-0.51，-0.03），p=0.02]。甜菜碱还与2型糖尿病发病率降低22％相关（IRR：0.78，95％CI：0.65，0.95）。左旋肉碱与空腹血糖降低相关[-0.68mg/dL(95%CI:-1.29,-0.07),p=0.03]和随访时HbA1c降低[-0.03％（95％CI：-0.05，-0.01），p<0.001],而TMAO与较高的空腹血糖[0.83mg/dL（95％CI：0.22，1.44）相关，p=0.01]和更高的甘油三酯[3.52mg/dL（95％CI：1.83，5.20），p<0.0001]。胆碱和TMAO均与2型糖尿病发病无关。（4）结论：较高的血浆甜菜碱与较低的血糖风险显示出一致的关联，胰岛素血症,和2型糖尿病。然而,TMAO,甜菜碱的代谢产物,与较高的葡萄糖和脂质浓度有关。这些观察结果证明了肠道微生物群代谢物对人类心脏代谢健康的重要性。
