Consolo Pierluigi, Giorgi Carlotta, Crisafulli Concetta, Fiorica Francesco, Pinton Paolo, Maurea Nicola, Missiroli Sonia, Quagliariello Vincenzo, Mantoan Beatrice, Ottaiano Alessandro, Pellicanò Giovanni Francesco, Orrù Germano, Scano Alessandra, Cacciola Irene, Pollicino Teresa, Di Mauro Giordana, Berretta Salvatore, Bignucolo Alessia, Toscano Enrica, Ciappina Giuliana, Berretta Massimiliano
Endoscopy Digestive Unit, Department of Clinical and Experimental Medicine, G. Martino University Hospital, University of Messina, 98122 Messina, Italy.
Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Int J Mol Sci. 2025 Aug 13;26(16):7823. doi: 10.3390/ijms26167823.
(), a Gram-negative anaerobe, is increasingly implicated in the pathogenesis of colorectal cancer (CRC) and inflammatory bowel disease (IBD). Its adhesin FadA enables epithelial adherence and invasion, promoting inflammation and tumorigenesis. has been shown to activate the NLRP3 inflammasome, leading to IL-1β release, and is associated with chemoresistance and poor prognosis in CRC. Additionally, lipid peroxidation markers such as malondialdehyde (MDA) and 4-hydroxy-nonenal (4-HNA) may contribute to inflammation-driven carcinogenesis. This study protocol aims to investigate the role of in the development and progression of IBD and CRC through integrated clinical, molecular, and imaging approaches. The protocol involves quantifying in tissue biopsies across disease stages and assessing correlations with inflammatory and oxidative markers. It will explore the bacterium's involvement in NLRP3 inflammasome activation, IL-1β production, and autophagy, and its potential contribution to chemoresistance. Furthermore, radiomic analysis of computed tomography (CT) images will be performed to identify imaging phenotypes associated with microbial load and inflammatory activity. Although primarily a protocol, the study includes preliminary in vitro data showing that exposure to FadA significantly increases inflammatory markers in Caco-2 cells, supporting the hypothesis that contributes to a pro-inflammatory, pro-tumorigenic microenvironment relevant to CRC progression.
（某革兰氏阴性厌氧菌）越来越多地被认为与结直肠癌（CRC）和炎症性肠病（IBD）的发病机制有关。其黏附素FadA可实现上皮细胞的黏附和侵袭，促进炎症和肿瘤发生。已证明（该菌）可激活NLRP3炎性小体，导致白细胞介素-1β释放，并与CRC中的化疗耐药性和不良预后相关。此外，脂质过氧化标志物如丙二醛（MDA）和4-羟基壬烯醛（4-HNA）可能促成炎症驱动的致癌作用。本研究方案旨在通过综合临床、分子和影像学方法，研究（该菌）在IBD和CRC发生发展中的作用。该方案包括对不同疾病阶段的组织活检中的（该菌）进行定量，并评估其与炎症和氧化标志物的相关性。它将探索该细菌在NLRP3炎性小体激活、白细胞介素-1β产生和自噬中的作用，以及其对化疗耐药性的潜在影响。此外，将对计算机断层扫描（CT）图像进行放射组学分析，以识别与微生物负荷和炎症活动相关的影像表型。尽管主要是一个方案，但该研究包括初步的体外数据，表明暴露于FadA会显著增加Caco-2细胞中的炎症标志物，支持了（该菌）促成与CRC进展相关的促炎、促肿瘤微环境这一假设。
