錳工程乳桿菌增強抗腫瘤和免疫調(diào)節(jié)活性用于結(jié)直腸癌的預防和治療

中文摘要：

基于益生菌的結(jié)直腸癌（CRC）生物療法因腫瘤靶向能力差和復雜腫瘤微環(huán)境中生物活性有限而面臨重大挑戰(zhàn)。本研究顯示，通過錳能夠增強乳酸乳球菌（Lactobacillus reuteri，L. reuteri）固有的生物活性，包括增殖、代謝和結(jié)腸定植，從而促成了錳工程菌株（MnLR）的構(gòu)建?？诜o藥MnLR及其代謝底物甘油（MnLR/Gly）可促進L. reuteri及其抗腫瘤代謝產(chǎn)物在結(jié)腸腫瘤中的富集。在多種前臨床結(jié)腸腫瘤模型中，單獨使用MnLR/Gly即可實現(xiàn)95.6%的原位腫瘤生長抑制、肝轉(zhuǎn)移減少62.1%，并提供持久保護，75%的預防性處理小鼠長期無腫瘤，62.5%對腫瘤再挑戰(zhàn)具有抵抗力。從機制上看，MnLR/Gly可誘導腫瘤內(nèi)及外周樹突狀細胞成熟、M1型巨噬細胞極化以及效應T細胞反應。在原位CRC兔模型中，GlyMnLR腸溶膠囊顯示出與標準化療相當?shù)娘@著抗腫瘤效果，同時表現(xiàn)出良好的安全性。這些發(fā)現(xiàn)表明，MnLR是一種有效的單獨益生菌療法，用于CRC的預防和治療。

英文摘要：

Probiotic-based biotherapy for colorectal cancer (CRC) faces significant challenges due to poor tumor-targeting and limited bioactivities within the complex tumor microenvironment. This study shows that Lactobacillus reuteri (L. reuteri)’s inherent bioactivities, including proliferation, metabolism, and colorectal colonization, can be enhanced by manganese, prompting the fabrication of a manganese-engineered strain (MnLR). Oral administration of MnLR with its metabolic substrate-glycerol (MnLR/Gly) promotes the enrichment of L. reuteri and its antitumor metabolites within colon tumors. Across multiple preclinical colon tumor models, MnLR/Gly alone achieves a 95.6% inhibition of orthotopic tumor growth, liver metastases reduction by 62.1%, and confers durable protection, with 75% of prophylactically treated mice remaining long-term tumor-free and 62.5% resisting tumor rechallenge. Mechanistically, MnLR/Gly induces both intratumoral and peripheral dendritic cell maturation, M1 macrophage polarization, and effector T-cell responses. In orthotopic CRC rabbit models, GlyMnLR enteric capsules demonstrate significant antitumor efficacy comparable to standard chemotherapy while exhibiting favorable safety. These findings highlight MnLR as an effective standalone probiotic therapy for CRC prevention and treatment.

論文信息：

論文題目：Manganese-engineered Lactobacillus Reuteri with enhanced antitumor and immunomodulatory activities for colorectal cancer prevention and treatment

期刊名稱：Nature Communications

時間期卷：17, Article number: 761(2026)

在線時間：2025年12月19日

DOI： doi.org/10.1038/s41467-025-67437-6

產(chǎn)品信息：

貨號：C-005

規(guī)格：5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes氯膦酸鹽脂質(zhì)體

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體在小鼠結(jié)腸癌模型清除巨噬細胞和外周單核巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Nature Communications：錳工程乳桿菌增強抗腫瘤和免疫調(diào)節(jié)活性用于結(jié)直腸癌的預防和治療。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除肺泡巨噬細胞和單核巨噬細胞的材料和方法：

In vivo cell depletion

clodronate-encapsulated liposomes (200?μl per mouse; LIPOSOMA, Netherlands) on days 6, 2, and 1 before tumor inoculation, and on days 4, 8, and 12 following tumor inoculation.

材料和方法文獻截圖：