原发性硬化性胆管炎（Primary sclerosing cholangitis，PSC）是一种与炎症性肠病（Inflammatory bowel disease，IBD）相关的进行性肝脏疾病。各项研究中，被诊断为PSC并合并IBD的患者比例差异较大。这引发了一个问题，即在没有症状的情况下，通过全面筛查是否所有的PSC患者都会显示肠道炎症。为了解答这个问题，我们在一项横断面研究中收集了健康对照组（n = 34）、PSC组（n = 25）、PSC-IBD组（n = 41）和IBD组（n = 51）的肠道活检样本，并进行了细胞因子表达分析、16S测序、深度组织学和内窥镜评分。我们发现，即使没有临床表现的IBD，绝大多数PSC患者的肠道活检样本显示免疫细胞浸润和IL17A和IFNG的表达增加。然而，IL10和FOXP3的表达也有所增加，这可能解释了为什么这些PSC患者仅在分子水平上出现肠道炎症。这种亚临床炎症主要集中在远端结肠，而PSC-IBD患者的炎症则可以出现在远端结肠或结肠右侧和回肠末端。此外，我们观察到没有合并IBD的PSC患者存在菌群失调的迹象，并与健康对照组相比具有明显特异的微生物组成。我们发现，绝大多数PSC患者即使没有合并IBD，在肠道炎症方面存在一个梯度。因此，需要进一步研究评估抗炎疗法对PSC患者的影响，以及其对临床表现的IBD和结直肠癌发生的影响。© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Primary sclerosing cholangitis (PSC) is a progressive liver disease associated with inflammatory bowel disease (IBD). The percentage of PSC patients diagnosed with concomitant IBD varies considerably between studies. This raises the question whether all PSC patients would show intestinal inflammation if screened thoroughly, even in the absence of symptoms.To address this question, we collected intestinal biopsies of healthy controls (n = 34), PSC (n = 25), PSC-IBD (n = 41), and IBD (n = 51) patients in a cross-sectional study and carried out cytokine expression profiling, 16S sequencing, in-depth histology, and endoscopy scoring.We found that the vast majority of PSC patients even without clinically manifest IBD showed infiltration of immune cells and increased expression of IL17A and IFNG in intestinal biopsies. However, expression of IL10 and FOXP3 were likewise increased, which may explain why these PSC patients have intestinal inflammation only on a molecular level. This subclinical inflammation in PSC patients was focused in the distal colon, whereas PSC-IBD patients showed inflammation either at the distal colon or on the right side of the colon and the terminal ileum. Furthermore, we observed that PSC patients without IBD showed signs of dysbiosis and exhibited a distinct microbial profile compared with healthy controls.We found a gradient of intestinal inflammation in the vast majority of PSC patients even in the absence of IBD. Thus, further studies evaluating the effect of anti-inflammatory therapies in PSC patients and their impact on the emergence of clinically manifest IBD and colorectal cancer development are needed.© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.