Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Gut Microbes. 2022 Jan-Dec;14(1):2003176. doi: 10.1080/19490976.2021.2003176.
Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal level responding to BBR alone or Prob+BBR treatment. Four genes encoding long-chain acyl-CoA synthetase were identified in the genome of this strain, and transcriptionally activated by BBR. BBR treatment further decreased the concentration of FFA in the culture medium of compared to vehicle. Thus, the activation of by BBR could enhance FFA import and mobilization in and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob () could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
非空腹血脂异常（nFL），主要由餐后血脂异常（PL）引起，最近被认为是空腹血脂异常（FL）的一个重要心血管疾病（CVD）风险因素。PL 是 2 型糖尿病（T2D）血脂异常的共同特征，尽管针对 PL 的有效治疗方法有限。在这项研究中，我们旨在评估通过改变肠道微生物组，益生菌（Prob）和黄连素（BBR）联合治疗是否能有效降低 T2D 患者的 PL，并探讨其潜在机制。在一项随机、安慰剂对照、多中心临床试验中，对来自 Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes（PREMOTE 研究）的 365 名 T2D 患者（100g 标准碳水化合物餐后 120 分钟）的 PL 进行了检查。与 BBR 或 Prob 单独治疗相比，Prob+BBR 治疗在改善餐后总胆固醇（pTC）和低密度脂蛋白胆固醇（pLDLc）水平方面更为有效，并且在 3 个月随访后，多种餐后脂质组代谢物的水平下降。这种效果与粪便中对 BBR 单独或 Prob+BBR 治疗的反应水平的变化有关。在该菌株的基因组中鉴定出了 4 个编码长链酰基辅酶 A 合成酶的基因，这些基因被 BBR 转录激活。与对照相比，BBR 处理进一步降低了该菌培养物中游离脂肪酸（FFA）的浓度。因此，BBR 对 的激活可以增强其对 FFA 的摄取和动员能力，减少腔内脂质的吸收，从而介导 Prob+BBR 对 PL 的作用。我们的研究证实，BBR 和 Prob（）对 PL 具有协同的降脂作用，作为肠道脂质库，可改善 T2D 患者的血脂异常和 CVD 风险控制。
