为了弥合超卫生研究小鼠模型与环境暴露条件相差较大的人体条件之间的差距，我们建立了一个实验室小鼠生态系统，使其在自然农场类型的栖息地中的全部环境因素下生活，我们称之为野生化过程。在之前的研究中，我们发现与传统饲养的实验室小鼠相比，野生化（Fer）小鼠对结直肠癌具有保护作用。然而，这种保护机制尚待阐明。破坏肠黏膜屏障是结直肠癌发生的一个已知因素，在本研究中我们评估了健康野生化C57BL/6JRj雄性小鼠的结肠黏膜屏障特性。尽管我们没有发现野生化对黏液层特性的影响，但更高表达的Fcgbp和Clca1基因仍然表明野生化加强了黏液的作用。其他参与细菌防御（Itln1，Ang1，Retnlb）和炎症机制（Zbp1，Gsdmc2）的蛋白质编码基因在野生化小鼠中也表达更高，进一步暗示野生化小鼠具有改变的肠黏膜屏障。这些发现表明通过在农场类型环境中的饲养所带来的微生物经验会改变小鼠的肠道屏障特性，从而可能更有效地保护其免受疾病的侵害。未来的研究应该通过蛋白质组学分析和野生化小鼠肠道屏障的体内表现来揭示野生化对肠道屏障的调节作用。© 2023. Springer Nature Limited.

To close the gap between ultra-hygienic research mouse models and the much more environmentally exposed conditions of humans, we have established a system where laboratory mice are raised under a full set of environmental factors present in a naturalistic, farmyard-type habitat-a process we have called feralization. In previous studies we have shown that feralized (Fer) mice were protected against colorectal cancer when compared to conventionally reared laboratory mice (Lab). However, the protective mechanisms remain to be elucidated. Disruption of the protective intestinal barrier is an acknowledged player in colorectal carcinogenesis, and in the current study we assessed colonic mucosal barrier properties in healthy, feralized C57BL/6JRj male mice. While we found no effect of feralization on mucus layer properties, higher expression of genes encoding the mucus components Fcgbp and Clca1 still suggested mucus enforcement due to feralization. Genes encoding other proteins known to be involved in bacterial defense (Itln1, Ang1, Retnlb) and inflammatory mechanisms (Zbp1, Gsdmc2) were also higher expressed in feralized mice, further suggesting that the Fer mice have an altered intestinal mucosal barrier. These findings demonstrate that microbial experience conferred by housing in a farmyard-type environment alters the intestinal barrier properties in mice possibly leading to a more robust protection against disease. Future studies to unravel regulatory roles of feralization on intestinal barrier should aim to conduct proteomic analyses and in vivo performance of the feralized mice intestinal barrier.© 2023. Springer Nature Limited.