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Abstract：
Fusobacterium nucleatum (F. nucleatum) is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of F. nucleatum in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of F. nucleatum related CRC (p < 0.01). In vitro studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of F. nucleatum. Moreover, chronic stress significantly increased the colon tumour burden of ApcMin/+ mice infected with F. nucleatum (p < 0.01), which was decreased by a catecholamine inhibitor (p < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of F. nucleatum related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.
摘要：
具核梭杆菌(F.核仁）与结直肠癌（CRC）的肿瘤发生密切相关。我们旨在研究宿主去甲肾上腺素对大肠癌中F.核仁致癌性的影响，并揭示其潜在机制。结果表明，去甲肾上腺素和细菌群体感应（QS）分子自诱导因子2（AI-2）均与F相关的CRC进展呈正相关（p<0.01）。体外研究,去甲肾上腺素可诱导QS相关基因的上调，并促进F的毒力和增殖。此外，慢性应激显著增加了ApcMin/+小鼠感染核仁F.的结肠肿瘤负荷(p<0.01),儿茶酚胺抑制剂降低了（p<0.001）。我们的发现表明，应激诱导的去甲肾上腺素可能通过细菌QS信号促进核仁F.相关CRC的进展。这些初步数据提供了通过靶向宿主激素-细菌QS王国间信号传导来管理病原菌的新策略。
