TY - JOUR

T1 - Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients

T2 - a double blinded placebo controlled randomized study

AU - Wang, Shujie

AU - Ren, Huahui

AU - Zhong, Huanzi

AU - Zhao, Xinjie

AU - Li, Changkun

AU - Ma, Jing

AU - Gu, Xuejiang

AU - Xue, Yaoming

AU - Huang, Shan

AU - Yang, Jialin

AU - Chen, Li

AU - Chen, Gang

AU - Qu, Shen

AU - Liang, Jun

AU - Qin, Li

AU - Huang, Qin

AU - Peng, Yongde

AU - Li, Qi

AU - Wang, Xiaolin

AU - Zou, Yuanqiang

AU - Shi, Zhun

AU - Li, Xuelin

AU - Li, Tingting

AU - Yang, Huanming

AU - Lai, Shenghan

AU - Xu, Guowang

AU - Li, Junhua

AU - Zhang, Yifei

AU - Gu, Yanyun

AU - Wang, Weiqing

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Type 2 diabetes

KW - probiotics

KW - berberine

KW - dyslipidemia

KW - postprandial lipidemia

KW - gut microbiome

KW - DENSITY-LIPOPROTEIN CHOLESTEROL

KW - TERM MORTALITY INSIGHT

KW - CHAIN FATTY-ACIDS

KW - CARDIOVASCULAR-DISEASE

KW - NONFASTING TRIGLYCERIDES

KW - GUT MICROBIOME

KW - HEART-FAILURE

KW - TRANSMEMBRANE MOVEMENT

KW - CONSENSUS STATEMENT

KW - AMERICAN-COLLEGE

U2 - 10.1080/19490976.2021.2003176

DO - 10.1080/19490976.2021.2003176

M3 - Journal article

C2 - 34923903

VL - 14

JO - Gut Microbes

JF - Gut Microbes

SN - 1949-0976

IS - 1

M1 - 2003176

ER -