The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration

  • Min-Gul Kim (Center for Clinical Pharmacology, Jeonbuk National University Hospital) ;
  • Suin Kim (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Ji-Young Jeon (Center for Clinical Pharmacology, Jeonbuk National University Hospital) ;
  • Seol Ju Moon (Center for Clinical Pharmacology, Jeonbuk National University Hospital) ;
  • Yong-Geun Kwak (Center for Clinical Pharmacology, Jeonbuk National University Hospital) ;
  • Joo Young Na (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • SeungHwan Lee (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Kyung-Mi Park (Genome and Company) ;
  • Hyo-Jin Kim (Genome and Company) ;
  • Sang-Min Lee (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Seo-Yeon Choi (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Kwang-Hee Shin (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2023.12.05
  • Accepted : 2023.12.22
  • Published : 2024.03.01
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Abstract

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Keywords

Acknowledgement

We appreciate Ms. Ye-ji Kang for participating in sample pretreatment and LC-MS/MS analysis.

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