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Original Article

Korean J Physiol Pharmacol 2024; 28(2): 153-164

Published online March 1, 2024

Copyright © Korean J Physiol Pharmacol.

Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration

Min-Gul Kim1,2,3, Suin Kim4, Ji-Young Jeon1, Seol Ju Moon1,2, Yong-Geun Kwak1,3, Joo Young Na5, SeungHwan Lee5, Kyung-Mi Park6, Hyo-Jin Kim6, Sang-Min Lee4, Seo-Yeon Choi4, and Kwang-Hee Shin4,*

1Center for Clinical Pharmacology, Jeonbuk National University Hospital, 2Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, 3Department of Pharmacology, School of Medicine, Jeonbuk National University, Jeonju 54907, 4College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, 5Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, 6Genome and Company, Seoungnam 13486, Korea

Correspondence to:Kwang-Hee Shin

Author contributions: M.G.K., S.H.L., K.M.P., H.J.K., and K.H.S. conceived and designed design of study. J.Y.J., S.J.M., J.Y.N., and S.K. carried acquisition of data. S.K., S.M.L., S.Y.C., and K.H.S. performed metabolomics, microbiota, immunogenicity, hematological, and statistical analyses and interpreted data. M.G.K., S.K., Y.G.K., and K.H.S. drafted the manuscript. M.G.K. and K.H.S. revised the manuscript critically for important intellectual content.

Received: December 5, 2023; Revised: December 18, 2023; Accepted: December 22, 2023


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: Biological products, Gastrointestinal microbiome, Lactococcus lactis, Metabolomics, Microbiota