中文摘要：
肠道菌群与结直肠癌（CRC）的发生发展密切相关。本研究发现，H. hathewayi——一种此前被报道与CRC相关的共生菌——在自发性CRC模型中反而对肠道肿瘤生长和肠道菌群失调具有保护作用。H. hathewayi可减缓同种异体移植结肠癌细胞的生长，并抑制ApcMin/+ 小鼠的CRC进展，同时伴随瘤内 CD14b+ 肿瘤相关巨噬细胞（TAMs）增多。这种保护效应归因于 H. hathewayi 分泌至 Hh.CM 中的蛋白，我们鉴定出一种含细胞壁结合重复序列的蛋白（CWBR-CP）是关键功能介质。CWBR-CP 在多种小鼠模型中重现了 H. hathewayi 的抑瘤效果，并诱导巨噬细胞向 M1 样极化转变。机制上，CWBR-CP 直接结合激肽释放酶 8（KLK8）并下调其在巨噬细胞中的表达。KLK8 的下调进而激活缓激肽受体 B1（B1R），触发 PI3K/AKT/NF-κB 通路，最终促进 M1 型巨噬细胞极化。
英文摘要：
Gut microbiota has been widely implicated in colorectal cancer (CRC). Here, we show that H. hathewayi, a commensal bacterium previously associated with CRC, is protective against intestinal tumor growth, and gut dysbiosis in a spontaneous CRC model. H. hathewayi attenuated the growth of allografted colon carcinoma cells and suppressed CRC progression in ApcMin/+ mice, concomitant with an increased intratumoral CD14b+ tumor-associated macrophages (TAMs). Such protective effect was attributed to H. hathewayi-secreted proteins from Hh.CM, and we identified a cell wall-binding repeat-containing protein (CWBR-CP) as the key functional mediator. CWBR-CP recapitulated the tumor suppression of H. hathewayi in multiple mouse models and induced a corresponding shift toward M1-like macrophage polarization. Mechanistically, CWBR-CP directly bound to kallikrein 8 (KLK8) and downregulated its expression in macrophages. KLK8 downregulation, in turn, activated bradykinin receptor B1 (B1R), triggering the PI3K/AKT/NF-κB pathway and ultimately promoting M1 macrophage polarization.
论文信息：
论文题目：A secreted protein from Hungatella hathewayi inhibits colorectal cancer by reprogramming intratumoral CD14b+ macrophages
期刊名称：PNAS
时间期卷：
Doi：10.1016/j.celrep.2026.117988
产品信息：
货号：CP-010-010
规格：10ml+10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除APC-Min 小鼠巨噬细胞，APC-Min 小鼠是携带 Apc 基因多发性肠道肿瘤（Min）突变的杂合小鼠。纯合小鼠会致死。 这种小鼠能自发产生 肠道腺瘤，并在生存、生长、摄食量和 肠道病变 等方面表现出 肠癌疾病 的特征。 因此，APC-Min 小鼠可用于研究家族性腺瘤息肉病（FAP）、结直肠癌等肿瘤或肿瘤相关疾病，以及 Wnt/β-catenin 信号通路的调控机制。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Cell Reports：一种源自 Hungatella hathewayi 的分泌蛋白通过重编程瘤内CD14b+巨噬细胞抑制结直肠癌。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
For the macrophage depletion model, male ApcMin/+ mice were orally gavaged with an oral administration of live H. hathewayi (1.0 × 108 CFU per mouse) in 0.1 mL sterile saline containing 2.5% glycerol for 9 weeks (n = 6). During this process, the mice were injected (i.p) with PBS liposomes and clodronate liposomes (LIPOSOMA) every two weeks and body weight and bleeding score were assessed daily.
巨噬细胞清除材料和方法文献截图：
