Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR’s cholesterol-decreasing efficacy in patients
| Autor: | Ying Zhao, Le Sun, Chongming Wu, Ying-Ying Zhang, Baoli Zhu, Yanan Yang, Peng Guo, Fang Zhang, Yuan-Yuan Yang, Wenquan Su, Jiaqi Yu, Sheng-Xian Wu, Yao-Xian Wang |
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| Rok vydání: | 2022 |
| Předmět: |
Berberine
medicine.drug_class Antibiotics Blood lipids Hyperlipidemias Pharmacology Gut flora digestive system Mice chemistry.chemical_compound medicine Animals Humans In patient Alistipes Multidisciplinary Bacteria biology Cholesterol business.industry Fecal bacteriotherapy biology.organism_classification Gastrointestinal Microbiome chemistry business |
| Zdroj: | Journal of Advanced Research. 37:197-208 |
| ISSN: | 2090-1232 |
| Popis: | Introduction Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)’s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation. Objectives This study aims to confirm the causal role of the gut microbiota in BBR’s anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness. Methods The correlation between gut microbiota and BBR’s inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR’s anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis. Results Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy. Conclusion The gut microbiota is necessary and sufficient for BBR’s hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy. |
| Databáze: | OpenAIRE |
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