Immunoactive Tripeptide RMK Alters T-Cell Subset Proportions and Remodels the Gut Microbiome–Metabolite Axis in S180 Tumor-Bearing Mice
- 1Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center for Nutrition, Health, and Ecological Security of Food Resources in the Yellow River Basin, Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China
- 2College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China
- 3School of Food and Bioengineering, Yantai Institute of Technology, Yantai 264003, China
Abstract
Background: Immunoactive peptides are emerging as safe oral immunomodulators, but whether a single tripeptide can alter T-cell subsets and the gut microbiome–metabolite axis is unclear. Methods: The synthetic tripeptide RMK (Arg–Met–Lys; HPLC purity >98%) was given orally once daily to S180 sarcoma-bearing Kunming mice from 7 days before to 14 days after tumor inoculation, a host-preconditioning plus continuous-exposure regimen. Results: RMK reduced tumor growth at both doses (inhibitory rates 40.03% and 48.58%), attenuated thymic atrophy and splenomegaly, and was accompanied by higher proportions of thymic CD4+CD8+ double-positive cells, splenic CD4+ and CD8+ T cells and tumor-infiltrating CD8+ T cells. Tumor-derived suspensions showed mitochondrial depolarization and ROS accumulation, readouts of mitochondrial and redox status that do not identify a cell-death pathway. 16S rRNA sequencing showed higher relative abundances of Lachnospiraceae and Ruminococcaceae, although community structure did not differ significantly. Untargeted metabolomics showed altered bile acid, sphingolipid and steroid-hormone metabolites, with lower aldosterone and cortisol than in tumor-bearing controls. Molecular docking, as an exploratory prediction only, gave the most favorable poses for MHC-I/II (H-2Kb, ΔG = −7.09 kcal/mol) and TCR-proximal kinases (AKT1, ZAP-70, Lck). Conclusions: These findings identify RMK as a candidate oral immunomodulatory peptide whose site of action remains to be defined.
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BibTeX
@article{han2026immunoactive,
title = {{Immunoactive Tripeptide RMK Alters T-Cell Subset Proportions and Remodels the Gut Microbiome–Metabolite Axis in S180 Tumor-Bearing Mice}},
author = {Rong Han and Qiuning Yang and Zhenjia Sun and Decheng Mao and Wenjie Ding and Yuemeng Wang and Haiyu Ji and Tian Wang},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213628},
url = {https://www.mdpi.com/2072-6643/18/21/3628},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunoactive Tripeptide RMK Alters T-Cell Subset Proportions and Remodels the Gut Microbiome–Metabolite Axis in S180 Tumor-Bearing Mice
AU - Rong Han
AU - Qiuning Yang
AU - Zhenjia Sun
AU - Decheng Mao
AU - Wenjie Ding
AU - Yuemeng Wang
AU - Haiyu Ji
AU - Tian Wang
PY - 2026
DA - 2026/10/31
JO - Nutrients
DO - 10.3390/nu18213628
UR - https://www.mdpi.com/2072-6643/18/21/3628
AB - Background: Immunoactive peptides are emerging as safe oral immunomodulators, but whether a single tripeptide can alter T-cell subsets and the gut microbiome–metabolite axis is unclear. Methods: The synthetic tripeptide RMK (Arg–Met–Lys; HPLC purity >98%) was given orally once daily to S180 sarcoma-bearing Kunming mice from 7 days before to 14 days after tumor inoculation, a host-preconditioning plus continuous-exposure regimen. Results: RMK reduced tumor growth at both doses (inhibitory rates 40.03% and 48.58%), attenuated thymic atrophy and splenomegaly, and was accompanied by higher proportions of thymic CD4+CD8+ double-positive cells, splenic CD4+ and CD8+ T cells and tumor-infiltrating CD8+ T cells. Tumor-derived suspensions showed mitochondrial depolarization and ROS accumulation, readouts of mitochondrial and redox status that do not identify a cell-death pathway. 16S rRNA sequencing showed higher relative abundances of Lachnospiraceae and Ruminococcaceae, although community structure did not differ significantly. Untargeted metabolomics showed altered bile acid, sphingolipid and steroid-hormone metabolites, with lower aldosterone and cortisol than in tumor-bearing controls. Molecular docking, as an exploratory prediction only, gave the most favorable poses for MHC-I/II (H-2Kb, ΔG = −7.09 kcal/mol) and TCR-proximal kinases (AKT1, ZAP-70, Lck). Conclusions: These findings identify RMK as a candidate oral immunomodulatory peptide whose site of action remains to be defined.
SN - 2072-6643
ER -