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Peer-reviewedCC BYNutrients

VSL#3 Co-Administration Is Associated with Altered Early-Phase Obeticholic Acid Exposure in MASLD Mice

  • A-Hyeon Lee1
  • Seung Min Lee2,3
  • In Young Kang3
  • Gye Ryeol Park3
  • Hye Hyun Yoo4
  • Jun Sang Yu5,6
  • Hyun Sung Kim7
  • Ji-Hee Shin8
  • Young-Do Nam8
  • Eileen Laurel Yoon3,9
  • Dae Won Jun3,9
9 affiliations
  1. 1Center for Nucleic Acid Therapies at the Department of Chemistry Institute for Chemical Epigenetics, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany
  2. 2Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea
  3. 3Department of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang University, Seoul 04763, Republic of Korea
  4. 4Pharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University,Ansan 15588, Republic of Korea
  5. 5Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan 15588, Republic of Korea
  6. 6College of Pharmacy, Jeju National University, Jeju 63243, Republic of Korea
  7. 7Department of Pathology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea
  8. 8Research Group of Personalized Diet, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea
  9. 9Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
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Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, and its global incidence continues to increase. MASLD can progress from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, effective preventive and therapeutic options remain limited. In this study, obeticholic acid (OCA) and the probiotic mixture VSL#3 were co-administered to a mouse model of MASLD to modulate gut microbiota and bile acid metabolism. Methods: Male C57BL/6 mice were fed a WD to induce MASLD and treated with OCA, VSL#3, or both. Gut microbiota was analyzed by 16S rRNA sequencing, bile acid (BA) composition was assessed by LC–MS/MS, hepatic and intestinal gene expression was determined by quantitative real-time PCR (qPCR) and immunohistochemistry, and unconjugated OCA pharmacokinetics (PK) were evaluated. Results: VSL#3-containing groups showed differences in selected taxa with reported bile salt hydrolase (BSH) potential and in BA composition, including a numerical shift toward higher levels of deconjugated BAs. Co-administration of OCA and VSL#3 was accompanied by lower hepatic steatosis, numerically favorable serum markers of liver injury, and lower cholesterol and total bilirubin levels. In addition, mice receiving VSL#3 showed numerically higher early plasma concentrations of unconjugated OCA. Lower intestinal ATP-binding cassette subfamily C member 2 (Abcc2) expression was also observed as a separate exploratory finding. Conclusions: The co-administration of VSL#3 with OCA was accompanied by exploratory differences in selected biological parameters and early-phase unconjugated OCA exposure. Lower intestinal Abcc2/Mrp2 expression was observed as a separate exploratory finding, and no functional relationship between intestinal transporter expression and OCA pharmacokinetics was established.

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Cite

BibTeXRIS
BibTeX
@article{lee2026vsl3,
  title = {{VSL#3 Co-Administration Is Associated with Altered Early-Phase Obeticholic Acid Exposure in MASLD Mice}},
  author = {A-Hyeon Lee and Seung Min Lee and In Young Kang and Gye Ryeol Park and Hye Hyun Yoo and Jun Sang Yu and Hyun Sung Kim and Ji-Hee Shin and Young-Do Nam and Eileen Laurel Yoon and Dae Won Jun},
  journal = {Nutrients},
  year = {2026},
  month = oct,
  doi = {10.3390/nu18193296},
  url = {https://europepmc.org/article/PMC/PMC13667209},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - VSL#3 Co-Administration Is Associated with Altered Early-Phase Obeticholic Acid Exposure in MASLD Mice
AU  - A-Hyeon Lee
AU  - Seung Min Lee
AU  - In Young Kang
AU  - Gye Ryeol Park
AU  - Hye Hyun Yoo
AU  - Jun Sang Yu
AU  - Hyun Sung Kim
AU  - Ji-Hee Shin
AU  - Young-Do Nam
AU  - Eileen Laurel Yoon
AU  - Dae Won Jun
PY  - 2026
DA  - 2026/10/01
JO  - Nutrients
DO  - 10.3390/nu18193296
UR  - https://europepmc.org/article/PMC/PMC13667209
AB  - Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, and its global incidence continues to increase. MASLD can progress from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, effective preventive and therapeutic options remain limited. In this study, obeticholic acid (OCA) and the probiotic mixture VSL#3 were co-administered to a mouse model of MASLD to modulate gut microbiota and bile acid metabolism. Methods: Male C57BL/6 mice were fed a WD to induce MASLD and treated with OCA, VSL#3, or both. Gut microbiota was analyzed by 16S rRNA sequencing, bile acid (BA) composition was assessed by LC–MS/MS, hepatic and intestinal gene expression was determined by quantitative real-time PCR (qPCR) and immunohistochemistry, and unconjugated OCA pharmacokinetics (PK) were evaluated. Results: VSL#3-containing groups showed differences in selected taxa with reported bile salt hydrolase (BSH) potential and in BA composition, including a numerical shift toward higher levels of deconjugated BAs. Co-administration of OCA and VSL#3 was accompanied by lower hepatic steatosis, numerically favorable serum markers of liver injury, and lower cholesterol and total bilirubin levels. In addition, mice receiving VSL#3 showed numerically higher early plasma concentrations of unconjugated OCA. Lower intestinal ATP-binding cassette subfamily C member 2 (Abcc2) expression was also observed as a separate exploratory finding. Conclusions: The co-administration of VSL#3 with OCA was accompanied by exploratory differences in selected biological parameters and early-phase unconjugated OCA exposure. Lower intestinal Abcc2/Mrp2 expression was observed as a separate exploratory finding, and no functional relationship between intestinal transporter expression and OCA pharmacokinetics was established.
SN  - 2072-6643
ER  -