肠系膜脂肪组织（mAT）增生，称为蠕动脂肪，是克罗恩病（CD）的病理特征。在我们之前报道的队列中，我们观察到肺无色杆菌是从蠕动脂肪中培养的最丰富和最普遍的细菌。使用了mAT衍生的肺无色杆菌的T3SS直系同源物的全基因组测序和鉴定。功能性 III 型分泌系统 (T3SS) 在体外和小鼠结肠炎模型中介导肺曲霉的致病潜力。此外，还引入了 T3SS Finder 管道来评估 CD 患者、溃疡性结肠炎和结直肠癌患者粪便中的肠道细菌 T3SS 直系同源物。在这里，我们发现 mAT 衍生的肺曲霉具有功能性 T3SS，通过 T3SS 加重小鼠结肠炎，并通过巨噬细胞和上皮细胞中不依赖半胱天冬酶的机制表现出 T3SS 依赖性细胞毒性，这证明了携带 T3SS 的肺曲霉具有致病潜力。宏基因组分析表明，与健康对照相比，克罗恩病患者粪便中无色杆菌的丰度有所增加。对各种肠道疾病中微生物总vT3SS丰度的综合比较表明，CD患者、溃疡性结肠炎患者和结直肠癌患者的粪便样本中均显示出vT3SS基因的特异性富集，并且在CD中发现并验证了10种基于T3SS基因的CD生物标志物。一个新招募的 CD 队列。此外，纯肠内营养 (EEN) 治疗（一种改善 CD 患者症状的干预措施）被发现与粪便样本中 T3SS 基因患病率的显着降低相关。这些发现强调了 T3SS 在 CD 和 CD 背景下的致病意义。鉴定可能作为诊断和监测 CD 患者临床状态的生物标志物的特定 T3SS 基因。这项工作得到了中国国家重点研发计划 (2020YFA0907800)、中国博士后科学基金 (2023M744089)、国家国家自然科学基金项目（32000096）、深圳市科技计划项目（KQTD20200820145822023、RCIC20231211085944057、ZDSYS20220606100803007）、国家临床重点学科、广东省消化疾病临床医学研究中心（2020B1111170004） ），中国克罗恩病庆丰科研基金

Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn's disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat.A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis in vitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients.Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples.These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients.This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn's & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.