Improved prebiotic-based "shield" equipped probiotics for enhanced colon cancer therapy by polarizing M1 macrophages and regulating intestinal microbiota.
10.1016/j.apsb.2025.05.040
- Author:
Yang WANG
1
;
Xiaomin SU
1
;
Yao LIU
2
;
Lina HU
3
;
Lin KANG
3
;
Ce XU
1
;
Zanya SUN
1
;
Chenyu SUN
1
;
Huishu GUO
1
;
Shun SHEN
3
Author Information
1. Central Laboratory, First Affiliated Hospital, Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116011, China.
2. Clinical Oncology Center, Shanghai Municipal Hospital of TCM, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
3. Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.
- Publication Type:Journal Article
- Keywords:
Colon cancer;
Lactobacillus reuteri;
M1 macrophage;
NLRP3;
Short-chain fatty acids
- From:
Acta Pharmaceutica Sinica B
2025;15(8):4225-4247
- CountryChina
- Language:English
-
Abstract:
Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.
