ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Systems Microbiology
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1547964
Colonizable probiotic Lactobacillus paracasei R3 enhances ICI therapy via modulating PBMCs differentiation
Provisionally accepted
- 1The People's Hospital of Chizhou, Chizhou, China
- 2Guangdong Medical University Dongguan, China, Dongguan, China
- 3Center of Human Microecology Engineering and Technology of Guangdong Province, Guangzhou, China
- 4Graduate school, Guangdong Medical University, Dongguan, China
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Lactobacillus paracasei R3 (L.p R3) has been reported to be effective to improve antitumour therapy for antitumour treatment in immune checkpoint inhibitor (ICI) therapy for colorectal cancer. However, the mechanisms behind this remain unclear. The present study shows that L.p R3 significantly enhanced antitumour efficacy ICI therapies in various tumour. Our results also showed the rapid adherence of L.p R3 to intestinal epithelial cell membrane, and promoted intestinal epithelial cell expression of mucin mRNA, led to the long maintenance of L.p R3 in colon and cecum in mice. L.p R3 significantly elevated the levels of macrophages, CD4+T cells and CD8+T cells in PBMCs while simultaneously decreasing the level of programmed cell death-1 (PD-1) on the surface of CD4+T cells and CD8+T cells. In addition, indole-3-carboxaldehyde, a metabolite of L.p R3 serves as an aryl hydrocarbon receptor (AHR) ligand regulating immune responses, was significantly upregulated in the serum of mice orally treated with L.p R3. In summary, our findings provide novel insights into the immune 2 regulation of probiotics in antitumour responses and present a potential avenue for L.p R3 in promoting ICI efficacy.
Keywords: Lactobacillus paracasei R3, ICI therapy, colonization, metabolite, Tumor inhibition
Received: 20 Dec 2024; Accepted: 10 Apr 2025.
Copyright: © 2025 Song, Liu, Yang, Chen, Zhu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiayi Zhu, Center of Human Microecology Engineering and Technology of Guangdong Province, Guangzhou, China
Xia Liu, Guangdong Medical University Dongguan, China, Dongguan, China
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