Hua Dengxiong, Yang Qin, Li Xiaowei, Zhou Xuexue, Kang Yingqian, Zhao Yan, Wu Daoyan, Zhang Zhengrong, Li Boyan, Wang Xinxin, Qi Xiaolan, Chen Zhenghong, Cui Guzhen, Hong Wei
Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou, Guizhou Medical University, Guiyang, China.
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & School/Hospital of Stomatology Guizhou Medical University, Guiyang, Guizhou, China.
mSystems. 2025 Feb 18;10(2):e0156724. doi: 10.1128/msystems.01567-24. Epub 2025 Jan 22.
The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as (CB) or (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.
Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.
肠道微生物群与炎症性肠病（IBD）和结直肠癌（CRC）密切相关。益生菌如[具体名称1]（CB）或[具体名称2]（AKK）有治疗炎症性肠病（IBD）或结直肠癌（CRC）的潜力。然而，关于CB和AKK联合治疗IBD或CRC的效果及免疫调节机制的研究尚未开展。本研究评估CB和AKK联合给药治疗DSS/AOM诱导的IBD和结肠炎相关CRC的潜力。我们的结果表明，与单一给药相比，CB和AKK联合给药不仅能显著减轻IBD小鼠体重减轻、结肠缩短和疾病活动指数升高等症状，还能调节肠道微生物群组成并有效抑制结肠炎症反应。在结肠炎相关CRC小鼠模型中，CB和AKK联合使用可显著减轻体重减轻，并显著减少结肠中巨噬细胞和细胞毒性T淋巴细胞（CTL）的炎症浸润，从而调节抗肿瘤免疫并抑制炎症诱导的CRC的发生。此外，我们发现CB和AKK联合益生菌疗法可增强结肠炎相关CRC小鼠对免疫检查点抑制剂抗小鼠PD-L1（aPD-L1）的敏感性，显著提高免疫治疗的抗肿瘤疗效和结肠炎相关CRC小鼠的生存率。此外，粪便微生物群移植疗法表明，将CB和AKK联合给药治疗的CRC小鼠的粪便移植到其他CRC小鼠中可减轻结肠中的肿瘤负荷并显著延长其生存率。我们的研究表明，两种益生菌CB和AKK联合使用不仅可以减轻慢性肠道炎症，还可以抑制向CRC的进展。这可能是一种支持肠道微生物群并增强宿主抗癌免疫力的天然且相对安全的方法。
我们的研究表明，与单一益生菌菌株相比，CB和AKK益生菌联合给药在预防IBD进展为CRC方面具有很大前景。这种协同效应归因于这种益生菌组合更有效地调节肠道微生物群、抑制炎症反应、增强免疫治疗方法的疗效以及通过粪便微生物群移植优化治疗结果的能力。
