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

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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.

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Most cited references 74

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Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.

(2002)

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Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

The Emerging Risk Factors Collaboration, George Davey Smith (2011)

Summary Background Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. Methods We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. Findings Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8·49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2·00 (95% CI 1·83–2·19) for coronary heart disease; 2·27 (1·95–2·65) for ischaemic stroke; 1·56 (1·19–2·05) for haemorrhagic stroke; 1·84 (1·59–2·13) for unclassified stroke; and 1·73 (1·51–1·98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40–59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10–12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3·90 mmol/L and 5·59 mmol/L. Compared with fasting blood glucose concentrations of 3·90–5·59 mmol/L, HRs for coronary heart disease were: 1·07 (0·97–1·18) for lower than 3·90 mmol/L; 1·11 (1·04–1·18) for 5·60–6·09 mmol/L; and 1·17 (1·08–1·26) for 6·10–6·99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. Interpretation Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. Funding British Heart Foundation, UK Medical Research Council, and Pfizer.

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Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

Fredrik Bäckhed, Josefine Roswall, Yangqing Peng … (2015)

The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.

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Journal ID (nlm-ta): Gut Microbes

Journal ID (iso-abbrev): Gut Microbes

Title: Gut Microbes

Publisher: Taylor & Francis

ISSN (Print): 1949-0976

ISSN (Electronic): 1949-0984

Publication date (Electronic, pub): 20 December 2021

Publication date (Electronic, collection): 2022

Publication date PMC-release: 20 December 2021

Volume: 14

Issue: 1

Electronic Location Identifier: 2003176

Affiliations

[a ]Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; , Shanghai, China

[b ]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

[c ]BGI-Shenzhen; , Shenzhen, China

[d ]Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen; , Copenhagen, Denmark

[e ]Dalian Institute of Chemical Physics, Chinese Academy of Science; , Dalian, China

[f ]Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine; , Shanghai, China

[g ]Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University; , Zhejiang Province, China

[h ]Nanfang Hospital, Southern Medical University; , Guangdong Province, China

[i ]Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine; , Shanghai, China

[j ]Department of Endocrinology, Central Hospital of Minhang District; , Shanghai, China

[k ]Department of Endocrinology, Qilu Hospital of Shandong University; , Shandong Province, China

[l ]Department of Endocrinology, Fujian Provincial Hospital; , Fujian Province, China

[m ]Department of Endocrinology, Shanghai Tenth People’s Hospital of Tong Ji University; , Shanghai, China

[n ]Department of Endocrinology, Xuzhou Central Hospital; , Jiangsu Province, China

[o ]Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine; , Shanghai, China

[p ]Chang Hai Hospital, Second Military Medical University; , Shanghai, China

[q ]Shanghai First People’s Hospital, Shanghai Jiao Tong University School of Medicine; , Shanghai, China

[r ]James D. Watson Institute of Genome Sciences; , Hangzhou, China

[s ]Johns Hopkins University School of Medicine; , Baltimore, Maryland, USA

Author notes

CONTACT Junhua Li lijunhua@ 123456genomics.cn BGI-Shenzhen, Shenzhen, China;

Yifei Zhang feifei@ 123456163.com Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

Yanyun Gu guyanyun@ 123456sjtu.edu.cn Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China;

Weiqing Wang, wqingw@ 123456163.com Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

[&]

These authors contributed equally: Shujie Wang; Huahui Ren; Huanzi Zhong

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Yanyun Gu https://orcid.org/0000-0002-4323-1648

Article

Publisher ID: 2003176

DOI: 10.1080/19490976.2021.2003176

PMC ID: 8726654

PubMed ID: 34923903

SO-VID: 7a827030-df19-4d4f-b2b6-773555ce6d3f

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

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Most cited references 74

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.

Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

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