School of Biomedicine, University of Adelaide, Adelaide.
Adelaide Dental School, University of Adelaide, Adelaide.
Int J Radiat Oncol Biol Phys. 2022 Jul 15;113(4):845-858. doi: 10.1016/j.ijrobp.2022.03.036. Epub 2022 Apr 8.
Due to its pivotal role in the modulation of immune and inflammatory responses, the gut microbiota has emerged as a key modulator of cancer treatment-induced gastrointestinal mucositis. However, it is not clear yet how it affects radiation therapy-induced oral mucositis (OM). As such, this study aimed to explore the gut microbiota's role in the pathogenesis of radiation-induced OM in rats.
Male Sprague Dawley rats were treated with 20 Gy x-ray radiation (Rx) delivered to the snout, with or without antibiotic-induced microbiota depletion (AIMD). OM severity was assessed, and tongue tissues were collected on day 9 and 15 postradiation for tissue injury and inflammatory markers assessment.
AIMD+Rx had a significantly shorter duration of severe OM compared with Rx alone group. Macroscopically, the tongue ulcer-like area was smaller in AIMD+Rx compared with the Rx group. Microscopically, a smaller percentage of the mucosal ulcer was observed in the dorsal tongue of AIMD+Rx compared with the Rx group. AIMD+Rx also had significantly lower levels of interleukin 6, interleukin 1 beta, and toll like receptor 4 in the tongue tissues than the Rx group.
The gut microbiota plays a role in OM pathogenesis, mainly in the recovery phase, through the modulation of proinflammatory pathways. Future microbiota-targeted interventions may improve OM in clinical settings.
由于其在调节免疫和炎症反应方面的关键作用,肠道微生物群已成为癌症治疗引起的胃肠道粘膜炎的关键调节剂。然而,它如何影响放射治疗引起的口腔粘膜炎(OM)尚不清楚。因此,本研究旨在探讨肠道微生物群在大鼠放射诱导 OM 发病机制中的作用。
雄性 Sprague Dawley 大鼠接受 20 Gy X 射线(Rx)照射鼻部,或接受抗生素诱导的微生物群耗竭(AIMD)加 Rx。评估 OM 严重程度,并在放射后第 9 天和第 15 天采集舌组织,用于组织损伤和炎症标志物评估。
与 Rx 组相比,AIMD+Rx 组的严重 OM 持续时间明显缩短。宏观上,AIMD+Rx 组的舌溃疡样区域小于 Rx 组。显微镜下,AIMD+Rx 组舌背黏膜溃疡的比例明显小于 Rx 组。AIMD+Rx 组舌组织中的白细胞介素 6、白细胞介素 1β和 toll 样受体 4 水平也明显低于 Rx 组。
肠道微生物群在 OM 的发病机制中起作用,主要在恢复阶段,通过调节促炎途径。未来针对微生物群的干预措施可能会改善临床 OM。