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Positive influence of gut microbiota on the effects of Korean red ginseng in metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial

Abstract

Background

Ginseng, a traditional herbal medicine, has been used for thousands of years to treat various diseases including metabolic syndrome (MS). However, the underlying mechanism(s) of such beneficial actions of ginseng against MS is poorly understood. Emerging evidence indicates a close association of the host gut microbiota with MS. The present study was conducted to examine, whether the beneficial effects of Korean red ginseng (KRG) against MS could be influenced by gut microbial population and whether gut microbial profile could be considered a valuable biomarker for targeted treatment strategy for MS in compliance with the predictive, preventive, and personalized medicine (PPPM / 3PM).

Methods

This clinical study was a randomized, double-blind, placebo-controlled trial evaluating the effects of KRG treatment for 8 weeks on patients with MS. The anthropometric parameters, vital signs, metabolic biomarkers, and gut microbial composition through 16S rRNA gene sequencing were assessed at the baseline and endpoint. The impact of KRG was also evaluated after categorizing the subjects into responders and non-responders, as well as enterotypes 1 and 2 based on their gut microbial profile at the baseline.

Results

Fifty out of 60 subjects who meet the MS criteria completed the trial without showing adverse reactions. The KRG treatment caused a significant decrease in systolic blood pressure (SBP). Microbial analysis revealed a decrease in Firmicutes, Proteobacteria, and an increase in Bacteroidetes in response to KRG. In patient stratification analysis, the responders showing marked improvement in the serum levels of lipid metabolic biomarkers TC and LDL due to the KRG treatment exhibited higher population of both the family Lachnospiraceae and order Clostridiales compared to the non-responders. The homeostasis model assessment-insulin resistance (HOMA-IR) and insulin level were decreased in enterotype 1 (Bacteroides-abundant group) and increased in enterotype 2 (prevotella-abundant group) following the KRG treatment.

Conclusion

In this study, the effects of KRG on the glucose metabolism in MS patients were influenced by the relative abundances of gut microbial population and differed according to the individual enterotype. Therefore, the analysis of enterotype categories is considered to be helpful in predicting the effectiveness of KRG on glucose homeostasis of MS patients individually. This will further help to decide on the appropriate treatment strategy for MS, in compliance with the perspective of PPPM.

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Availability of data and material

Data can be provided upon request from the journal.

Code availability

Related information was provided in the manuscript.

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Funding

This study was supported by the Korea Ginseng Corporation (Seoul, Republic of Korea) and by the Main Research Program (E0170601-04) of the Korea Food Research Institute funded by the Ministry of Science and ICT. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Contributions

E Seong contributed to manuscript writing and data analysis; S Bose, SY Han, and M Lee contributed to the manuscript review; E Song and Y Nam contributed to the microbial analysis; and H Kim contributed the overall research design and progress.

Corresponding authors

Correspondence to Young-Do Nam or Hojun Kim.

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Ethics approval and consent to participate

This trial was performed at Dongguk University-Ilsan Oriental Medical Hospital (Ilsan, Gyeonggi-do, Republic of Korea) from February 27, 2019, to February 21, 2020. The Institutional Review Board of the Hospital approved this study (approval number: DUIOH 2018–12-004). The study protocol was also registered in the Clinical Research Information Service online registration system (registration number: KCT0004823). It was conducted according to the principles of the Declaration of Helsinki. Voluntary written consent was obtained after providing a detailed explanation regarding the research to the participants.

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Not applicable.

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The authors declare no competing interests.

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Seong, E., Bose, S., Han, SY. et al. Positive influence of gut microbiota on the effects of Korean red ginseng in metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial. EPMA Journal 12, 177–197 (2021). https://doi.org/10.1007/s13167-021-00243-4

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Keywords

  • Korean red ginseng
  • Herbal medicine
  • Metabolic syndrome
  • Patient stratification
  • Blood serum
  • Biomarker panel
  • Molecular pathways
  • Oxidative stress
  • Inflammation
  • ROS detoxification
  • Lipid metabolic biomarkers
  • Hyperlipidemia
  • Glucose homeostasis
  • Insulin level
  • Anthropometric parameters
  • Vital signs
  • Fat mass
  • BMI
  • Gender
  • Predictive preventive personalized medicine (PPPM / 3PM)
  • Individual enterotype
  • Clinical trial
  • Gut microbiome profile
  • Drug response
  • Treatment strategy
  • Blood pressure
  • 16S rRNA gene sequencing
  • HOMA-IR