Identification of early processes leading to complex tissue pathologies, such as inflammatory bowel diseases, ‎poses a major scientific and clinical challenge that is imperative for improved diagnosis and treatment. Most studies of inflammation onset focus on cellular processes and signaling molecules, while overlooking the environment in which they take place, the continuously remodeled extracellular matrix. In this study, we used colitis models for investigating extracellular–matrix dynamics during disease onset, while treating the matrix as a complete and defined entity. Through the analysis of matrix structure, stiffness and composition, we unexpectedly revealed that even prior to the first clinical symptoms, the colon displays its own unique extracellular–matrix signature and found specific markers of clinical potential, which were also validated in human subjects. We also show that the emergence of this pre-symptomatic matrix is mediated by subclinical infiltration of immune cells bearing remodeling enzymes. Remarkably, whether the inflammation is chronic or acute, its matrix signature converges at pre-symptomatic states. We suggest that the existence of a pre-symptomatic extracellular–matrix is general and relevant to a wide range of diseases.

识别导致复杂组织病理学（例如炎症性肠病）的早期过程，提出了重大的科学和临床挑战，这对于改进诊断和治疗至关重要。大多数炎症发生的研究都集中在细胞过程和信号分子上，而忽视了它们发生的环境，即不断重塑的细胞外基质。在这项研究中，我们使用结肠炎模型来研究疾病发作期间的细胞外基质动力学，同时将基质视为完整且明确的实体。通过对基质结构、硬度和成分的分析，我们出乎意料地发现，即使在出现第一个临床症状之前，结肠就显示出自己独特的细胞外基质特征，并发现了具有临床潜力的特定标记，这也在人类受试者中得到了验证。我们还表明，这种症状前基质的出现是由携带重塑酶的免疫细胞的亚临床浸润介导的。值得注意的是，无论炎症是慢性还是急性，其基质特征都会收敛于症状前状态。我们认为，症状前细胞外基质的存在是普遍存在的，并且与多种疾病相关。