美国麻省理工学院和哈佛大学布罗德研究所Ramnik J. Xavier团队近期取得重要工作进展，他们报道了受空间限制的肠道免疫和微生物群驱动的适应。相关研究成果2024年11月20日在线发表于《自然》杂志上。

据介绍，肠道的特点是宿主对营养和水分吸收的需求，与建立对外界环境的耐受性的需求相匹配。为了更好地了解肠道在健康和疾病中的作用，人们已经做出了大量努力来表征来自不同肠道区域的细胞的特性和组成。然而，肠道在空间中的转录概况和细胞基础的稳健性、适应性和恢复力的程度仍然知之甚少。

研究人员生成了稳定和扰动状态下小鼠肠道的空间和细胞综合资源。利用这些数据，研究人员证明了肠道的空间概况对微生物群的影响是强大的，并且在空间受限的情况下具有适应性。通过部署时空急性炎症模型，研究人员证明了肠道环境的稳健性和适应性特征都是有弹性的。

此外，为了强调数据集的生理相关性和价值，研究人员确定了结肠中部的一个区域，其特征是结构细胞对微生物群的免疫驱动多细胞空间适应。

总之，这一研究结果表明，肠道区域化的特点是结构细胞状态稳健且有弹性，肠道可以通过免疫和结构细胞稳态之间的相互作用，以空间控制的方式适应环境压力。

附：英文原文

Title: Spatially restricted immune and microbiota-driven adaptation of the gut

Author: Mayassi, Toufic, Li, Chenhao, Segerstolpe, sa, Brown, Eric M., Weisberg, Rebecca, Nakata, Toru, Yano, Hiroshi, Herbst, Paula, Artis, David, Graham, Daniel B., Xavier, Ramnik J.

Issue&Volume: 2024-11-20

Abstract: The intestine is characterized by an environment in which host requirements for nutrient and water absorption are consequently paired with the requirements to establish tolerance to the outside environment. To better understand how the intestine functions in health and disease, large efforts have been made to characterize the identity and composition of cells from different intestinal regions1,2,3,4,5,6,7,8. However, the robustness, nature of adaptability and extent of resilience of the transcriptional landscape and cellular underpinning of the intestine in space are still poorly understood. Here we generated an integrated resource of the spatial and cellular landscape of the murine intestine in the steady and perturbed states. Leveraging these data, we demonstrated that the spatial landscape of the intestine was robust to the influence of the microbiota and was adaptable in a spatially restricted manner. Deploying a model of spatiotemporal acute inflammation, we demonstrated that both robust and adaptable features of the landscape were resilient. Moreover, highlighting the physiological relevance and value of our dataset, we identified a region of the middle colon characterized by an immune-driven multicellular spatial adaptation of structural cells to the microbiota. Our results demonstrate that intestinal regionalization is characterized by robust and resilient structural cell states and that the intestine can adapt to environmental stress in a spatially controlled manner through the crosstalk between immunity and structural cell homeostasis.

DOI: 10.1038/s41586-024-08216-z

Source: https://www.nature.com/articles/s41586-024-08216-z