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

  • Gut Microbes. 2022 Jan-Dec;14(1):2003176. doi: 10.1080/19490976.2021.2003176.
Shujie Wang  1  2 ,  Huahui Ren  3  4 ,  Huanzi Zhong  3 ,  Xinjie Zhao  5 ,  Changkun Li  1  2  6 ,  Jing Ma  6 ,  Xuejiang Gu  7 ,  Yaoming Xue  8 ,  Shan Huang  9 ,  Jialin Yang  10 ,  Li Chen  11 ,  Gang Chen  12 ,  Shen Qu  13 ,  Jun Liang  14 ,  Li Qin  15 ,  Qin Huang  16 ,  Yongde Peng  17 ,  Qi Li  5 ,  Xiaolin Wang  5 ,  Yuanqiang Zou  3 ,  Zhun Shi  3 ,  Xuelin Li  1  2 ,  Tingting Li  1  2 ,  Huanming Yang  3  18 ,  Shenghan Lai  19 ,  Guowang Xu  5 ,  Junhua Li  3 ,  Yifei Zhang  1  2 ,  Yanyun Gu  1  2 ,  Weiqing Wang  1  2
Affiliations
  • 1. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. 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.
  • 3. BGI-Shenzhen, Shenzhen, China.
  • 4. Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • 5. Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China.
  • 6. Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 7. Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China.
  • 8. Nanfang Hospital, Southern Medical University, Guangdong Province, China.
  • 9. Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 10. Department of Endocrinology, Central Hospital of Minhang District, Shanghai, China.
  • 11. Department of Endocrinology, Qilu Hospital of Shandong University, Shandong Province, China.
  • 12. Department of Endocrinology, Fujian Provincial Hospital, Fujian Province, China.
  • 13. Department of Endocrinology, Shanghai Tenth People's Hospital of Tong Ji University, Shanghai, China.
  • 14. Department of Endocrinology, Xuzhou Central Hospital, Jiangsu Province, China.
  • 15. Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 16. Chang Hai Hospital, Second Military Medical University, Shanghai, China.
  • 17. Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 18. James D. Watson Institute of Genome Sciences, Hangzhou, China.
  • 19. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
PMID: 34923903 DOI: 10.1080/19490976.2021.2003176
Abstract

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.

Keywords
Type 2 diabetes; berberine; dyslipidemia; gut microbiome; postprandial lipidemia; probiotics.
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