肠道稳态由特殊的宿主细胞和肠道微生物群共同维持。Wnt/β-联蛋白信号通路对胃肠道发育和稳态至关重要，其失调与炎症和结肠直肠癌有关。Axin1负调控激活的Wnt/β-联蛋白信号通路，但人们对其在调节健康和疾病宿主微生物相互作用中的关系知之甚少。在此，我们旨在证明肠道Axin1决定了肠道稳态和宿主对炎症的反应。根据人炎症性肠病数据集分析Axin1的表达。为探讨肠道Axin1在调节肠道稳态和结肠炎中的作用和机制，我们在肠上皮细胞（IEC；Axin1 ^∆IEC）和帕内特细胞（PC；Axin1 ^∆PC）中建立了条件敲除Axin1的新小鼠模型与对照组（Axin1 ^LoxP；LoxP：X-over位点，P1）小鼠。我们发现人炎症性肠病（IBD）的结肠上皮细胞中Axin1的表达增加，Axin1 ^∆IEC小鼠表现出杯状细胞空间分布的改变、PC形态改变、溶菌酶表达减少和嗜黏蛋白阿克曼菌（Akkermansia muciniphila, A. muciniphila）富集。肠上皮细胞和PC中Axin1的缺失降低了体内葡聚糖硫酸钠（DSS）诱导的结肠炎易感性。Axin1 ^∆IEC与Axin1 ^∆PC小鼠和对照组小鼠共同饲养后更易患葡聚糖硫酸钠（DSS）结肠炎。用嗜黏蛋白阿克曼菌治疗可降低DSS-结肠炎的严重程度。抗生素治疗并未改变Axin1 ^LoxP小鼠中的肠上皮细胞增殖。然而，与未经处理的Axin1 ^∆IEC小鼠相比，抗生素处理后的Axin1 ^∆IEC小鼠肠道增殖细胞减少。这些数据表明，肠道微生物群具有非致结肠炎性效应。总之，我们发现肠道Axin1的缺失可以预防结肠炎，这可能由上皮细胞Axin1和Axin1相关的嗜黏蛋白阿克曼菌驱动。我们的研究证明了Axin1在介导肠道稳态和微生物群中的新作用。进一步利用特异性的Axin1突变进行机制研究，阐明Axin1如何调节微生物群和宿主炎症反应，将为人IBD提供新的治疗策略。

Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host-microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1^ΔIEC) and Paneth cell (PC; Axin1^ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1^ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vivo. Axin1^ΔIEC and Axin1^ΔPC mice became more susceptible to DSS-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1^Loxp mice. However, the intestinal proliferative cells in Axin1^ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1^ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.