Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study
Shujie Wang,
Huahui Ren,
Huanzi Zhong,
Xinjie Zhao,
Changkun Li,
Jing Ma,
Xuejiang Gu,
Yaoming Xue,
Shan Huang,
Jialin Yang,
Li Chen,
Gang Chen,
Shen Qu,
Jun Liang,
Li Qin,
Qin Huang,
Yongde Peng,
Qi Li,
Xiaolin Wang,
Yuanqiang Zou,
Zhun Shi,
Xuelin Li,
Tingting Li,
Huanming Yang,
Shenghan Lai,
Guowang Xu,
Junhua Li,
Yifei Zhang,
Yanyun Gu,
Weiqing Wang
Affiliations
Shujie Wang
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Huahui Ren
BGI-Shenzhen
Huanzi Zhong
BGI-Shenzhen
Xinjie Zhao
Chinese Academy of Science
Changkun Li
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Jing Ma
Shanghai Jiao Tong University School of Medicine
Xuejiang Gu
The First Affiliated Hospital of Wenzhou Medical University
Yaoming Xue
Southern Medical University
Shan Huang
Shanghai Jiao Tong University School of Medicine
Jialin Yang
Central Hospital of Minhang District
Li Chen
Qilu Hospital of Shandong University
Gang Chen
Fujian Provincial Hospital
Shen Qu
Shanghai Tenth People’s Hospital of Tong Ji University
Jun Liang
Xuzhou Central Hospital
Li Qin
Shanghai Jiao Tong University School of Medicine
Qin Huang
Second Military Medical University
Yongde Peng
Shanghai Jiao Tong University School of Medicine
Qi Li
Chinese Academy of Science
Xiaolin Wang
Chinese Academy of Science
Yuanqiang Zou
BGI-Shenzhen
Zhun Shi
BGI-Shenzhen
Xuelin Li
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Tingting Li
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Huanming Yang
BGI-Shenzhen
Shenghan Lai
Johns Hopkins University School of Medicine
Guowang Xu
Chinese Academy of Science
Junhua Li
BGI-Shenzhen
Yifei Zhang
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Yanyun Gu
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Weiqing Wang
Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
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 Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
