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

Journal: Gut microbes 2022;14(1):2003176

PMID: 34923903

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Hyperlipidaemia is a major risk factor for atherosclerotic cardiovascular diseases particularly when combined with hyperglycaemia and type 2 diabetes (T2D). Current diagnostic criteria and treatment targets are based on evaluating fasting lipidaemia (FL). However, increasing evidence has supported that a high level of non-fasting lipidaemia, mainly constituted by post-prandial lipidaemia (PL), is also an important CVD risk factor. The aim of this study was to investigate how the combination treatment of berberine (BBR) and probiotics (Prob), or either one could exert benefit on lowering PL, and whether their impact on gut microbiota could contribute to this effect. This study is based on the PREMOTE trial, which was a randomised, double-blind, placebo-controlled clinical trial in 20 medical centres in China and enrolled newly diagnosed T2D patients. This lipidomic study included 365 of the 409 participants enrolled for the PREMOTE trial. Results showed that: - Prob+BBR combined therapy exerted a similar effect on reducing fasting lipidaemia with BBR alone but a superior effect on the levels of postprandial plasma total cholesterol and post-prandial low-density lipoprotein cholesterol compared to either BBR or Prob alone. - a substantial decrease in various lipid species after Prob+BBR treatment. Authors conclude that their findings proved the therapeutic effect of a combined treatment of oral administration of probiotics with berberine on improving PL in patients newly diagnosed with T2D and proposed a new gut microbiome related remedy for managing dyslipidaemia, covering both PL and FL, in patients with T2D.

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 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.

Address: 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.; BGI-Shenzhen, Shenzhen, China.; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.; BGI-Shenzhen, Shenzhen, China.; Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China.; 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.; Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China.; Nanfang Hospital, Southern Medical University, Guangdong Province, China.; Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Endocrinology, Central Hospital of Minhang District, Shanghai, China.; Department of Endocrinology, Qilu Hospital of Shandong University, Shandong Province, China.; Department of Endocrinology, Fujian Provincial Hospital, Fujian Province, China.; Department of Endocrinology, Shanghai Tenth People's Hospital of Tong Ji University, Shanghai, China.; Department of Endocrinology, Xuzhou Central Hospital, Jiangsu Province, China.; Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Chang Hai Hospital, Second Military Medical University, Shanghai, China.; Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; BGI-Shenzhen, Shenzhen, China.; James D. Watson Institute of Genome Sciences, Hangzhou, China.; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

DOI: 10.1080/19490976.2021.2003176

Patient Centred Factor

Mediators: Type 2 diabetes mellitus

Physical Environment

Infectious Agents

Clinical Imbalances

Hormonal Gastro-intestinal

Laboratory Testing

Blood Stool

Modifiable Lifestyle Factors

Diet

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Probiotics Cholesterol Gut microbiota Gut microbiome Type 2 diabetes Lipids Cardiovascular disease Dyslipidaemia Hyperlipidaemia Postprandial Lipidaemia

Bioactive Substances

Probiotics

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/diabetestype2.html

MeSH Terms: Adult, Animals, Berberine, Cholesterol, Cholesterol, LDL, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Feces, Female, Gastrointestinal Microbiome, Humans, Hyperlipidemias, Male, Middle Aged, Postprandial Period, Probiotics