Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine

Wang, Yan; Tong, Qian; Shou, Jia‐Wen; Zhao, Ziran; Li, Xiaoyang; Zhang, Xianfeng; Ma, Shu‐Rong; He, Chi‐Yu; Lin, Yuan; Wen, Bao‐Ying; Guo, Fang; Fu, Jie; Jiang, Jian‐Dong

doi:10.7150/thno.18290

Cited by 104 publications

(75 citation statements)

References 41 publications

(65 reference statements)

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“…Increased dietary protein, leading to increased arginine, could thus constitute a potential dietary intervention to improve digoxin efficacy. Recent data have also elucidated the role of diet‐induced changes in the gut microbiota on the oral bioavailability of the herbal supplement, berberine, used for the treatment of hyperlipidaemia and type 2 diabetes (Wang et al ., ). The bioavailability of berberine was significantly increased in high‐fat diet (HFD)‐fed hamsters in comparison to hamsters fed a normal diet.…”

Section: Gut Microbiota–drug Interactionsmentioning

confidence: 97%

Drug–gut microbiota interactions: implications for neuropharmacology

Walsh

Griffin

Clarke

et al. 2018

British J Pharmacology

103

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The fate and activity of drugs are frequently dictated not only by the host per se but also by the microorganisms present in the gastrointestinal tract. The gut microbiome is known to, both directly and indirectly, affect drug metabolism. More evidence now hints at the effects that drugs can have on the function and composition of the gut microbiome. Both microbiota-mediated alterations in drug metabolism and drug-mediated alterations in the gut microbiome can have beneficial or detrimental effects on the host. Greater insights into the mechanisms driving these reciprocal drug-gut microbiota interactions are needed to guide the development of microbiome-targeted dietary or pharmacological interventions, which may have the potential to enhance drug efficacy or reduce drug side effects. In this review, we explore the relationship between drugs and the gut microbiome, with a specific focus on potential mechanisms underpinning the drug-mediated alterations on the gut microbiome and the potential implications for psychoactive drugs. LINKED ARTICLES: This article is part of a themed section on When Pharmacology Meets the Microbiome: New Targets for Therapeutics? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.24/issuetoc.

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Section: Gut Microbiota–drug Interactionsmentioning

confidence: 97%

Drug–gut microbiota interactions: implications for neuropharmacology

Walsh

Griffin

Clarke

et al. 2018

British J Pharmacology

103

View full text Add to dashboard Cite

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“…Nutraceuticals containing BBR can significantly reduce plasma LDL-C levels of elderly statinintolerant hypercholesterolemic patients (Marazzi et al, 2011). Another study showed that when it plus low-dose statins and/or ezetimibe, most coronary artery disease (CHD) patients who were high-dose statin intolerant could achieve target LDL-C levels within 3 to 6 months (Marazzi et al, 2019).Of note, the therapeutic effects of BBR on these inflammatory and metabolic diseases, such as emergent mild diarrhea (Yue et al, 2019), ulcerative colitis (Cui et al, 2018), obesity (Xie et al, 2011;Zhang et al, 2015), hyperlipidemia (Wang et al, 2017) and diabetes , appeared to be related to the regulation of the gut microbiota.…”

Section: Introductionmentioning

confidence: 99%

Effect of Berberine on Atherosclerosis and Gut Microbiota Modulation and Their Correlation in High-Fat Diet-Fed ApoE−/− Mice

et al. 2020

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Atherosclerosis and its associated cardiovascular diseases (CVDs) are serious threats to human health and have been reported to be associated with the gut microbiota. Recently, the role of berberine (BBR) in atherosclerosis and gut microbiota has begun to be appreciated. The purposes of this study were to observe the effects of high or low doses of BBR on atherosclerosis and gut microbiota modulation, and to explore their correlation in ApoE −/− mice fed a high-fat diet. A significant decrease in atherosclerotic lesions was observed after treatment with BBR, with the effect of the high dose being more obvious. Both BBR treatments significantly reduced total cholesterol, APOB100, and very low-density lipoprotein cholesterol levels but levels of high/lowdensity lipoprotein cholesterol and lipoprotein (a) were only reduced by high-dose BBR. Decreased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6 and increased anti-inflammatory IL-10 and adiponectin levels were observed in the high-dose BBR group, but no decrease in IL-6 or increase in IL-10 was evident using the low-dose of BBR. 16S rRNA sequencing showed that BBR significantly altered the community compositional structure of gut microbiota. Specifically, BBR enriched the abundance of Roseburia, Blautia, Allobaculum, Alistipes, and Turicibacter, and changed the abundance of Bilophila. These microbiota displayed good anti-inflammatory effects related to the production of short-chain fatty acids (SCFAs) and were related to glucolipid metabolism. Alistipes and Roseburia were significantly enriched in high-dose BBR group while Blautia and Allobaculum were more enriched in low-dose, and Turicibacter was enriched in both BBR doses. Metagenomic analysis further showed an elevated potential for lipid and glycan metabolism and synthesis of SCFAs, as well as reduced potential of TMAO production after BBR treatment. The findings demonstrate that both high and low-dose BBR can improve serum lipid and systemic inflammation levels, and alleviate atherosclerosis induced by high-fat diet in ApoE −/− mice. The effects are more pronounced for the high dose. This anti-atherosclerotic effect of BBR may be partly attributed to changes in composition and functions of gut microbiota which may be associated with anti-inflammatory and metabolism of glucose and lipid. Notably, gut microbiota alterations showed different sensitivity to BBR dose.

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“…Recently, E. coli infection was observed to significantly reduce the absorption of orally administered enrofloxacin in broilers (Guo et al, 2014). Yan Wang reported that berberine treatment lowered blood lipids and glucose effectively only in the high-fat diet (HFD)-fed hamsters with increased levels of nitrate reductase (NR) activity in the gut microbiota (Wang et al, 2017). In our previous research work, liver injury affects the gut microbiome in rats, particularly by depleting the Lactobacillus, which is directly involved in the bioconversion of the GL.…”

Section: Discussionmentioning

confidence: 99%

“…Rats pretreated with L. murinus or normal saline (n = 6) were administered an oral (10 mg/kg) dose of GL dissolved in 0.5% sodium carboxymethyl cellulose (CMC-Na) (5 mg/ml) 24 h after completing the seven consecutive daily treatment with physiological saline (control) or L. murinus dissolved in physiological saline (1 × 10 9 CFU/mouse). Whole-blood samples were taken from the orbital vein into tubes with heparin sodium at 0.17, 0.33, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72 h after oral administration (Zhou et al, 2013;Wang et al, 2017). Plasma was harvested by centrifugation at 8,000 rpm for 10 min and stored at −20 • C until analyzed.…”

Section: Pharmacokinetic Experimentsmentioning

confidence: 99%

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

et al. 2020

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Intestinal microbiota has been extensively studied in the context of host health benefit, and it has recently become clear that the gut microbiota influences drug pharmacokinetics and correspondingly efficacy. Intestinal microbiota dysbiosis is closely related with liver cirrhosis, especially the depletion of Lactobacillus. Therefore, the bioavailability of orally administered glycyrrhizic acid (GL) was speculated to be influenced under a pathological state. In the present study, L. murinus was isolated and screened for GL bioconversion capacity in vitro. Compared with Lactobacillus rhamnosus and Lactobacillus acidophilus, L. murinus was chosen for further investigation because it has the highest biotransformation rate. Our results showed that L. murinus could significantly improve the translocation of GL on Caco-2 cell models. Meanwhile, L. murinus was observed to have the ability to bind with the surface of Caco-2 cells and prominently downregulate the transporter gene expression level of multidrug resistance gene 1 (MDR1) and multidrug resistance protein 2 (MRP2), which were involved in the efflux of drugs. Furthermore, L. murinus was selected to be orally administred into rats in healthy and liver cirrhosis groups by a daily gavage protocol. Our data highlighted that supplements of L. murinus significantly improved the bioavailability of orally administered GL in rats, especially under a pathological condition, which may provide a novel strategy for improving the clinical therapeutic effect of liver protective drugs.

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Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine

Cited by 104 publications

References 41 publications

Drug–gut microbiota interactions: implications for neuropharmacology

Drug–gut microbiota interactions: implications for neuropharmacology

Effect of Berberine on Atherosclerosis and Gut Microbiota Modulation and Their Correlation in High-Fat Diet-Fed ApoE−/− Mice

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

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