Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences, Pusan National University, Yangsan, South Korea.
Graduate Program of Genomic Data Sciences, Pusan National University, Yangsan, South Korea.
Front Immunol. 2022 Mar 24;13:737536. doi: 10.3389/fimmu.2022.737536. eCollection 2022.
Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibiotic exposure was assessed for its impact on renal distress as a sequela of platinum-based chemotherapy. Clinical transcriptome dataset-based evaluations demonstrated that levels of dysbiosis-responsive genes were elevated during renal distress, indicating pathological communications between gut and kidney. Experimentally, mucosal exposure to streptomycin aggravated platinum-induced renal tubular lesions in a mouse model. Moreover, antibiotic-induced dysbiosis increased susceptibility to gut mucosal inflammation, epithelial disruption, and bacterial exposure in response to cisplatin treatment. Further investigation of the luminal microbes indicated that antibiotic-induced dysbiosis promoted the dominance of species. Moreover, the functional assessment of dysbiotic microbiota predicted tryptophan metabolic pathways. In particular, dysbiosis-responsive was associated with the production of the uremic toxin indoxyl sulfate and renal injuries. The results of this study including bacterial community-based evaluations provide new predictive insights into the interorgan communications and interventions against dysbiosis-associated disorders.
流行病学和实验证据表明，抗生素暴露与各种疾病的易感性之间存在密切关联。临床上，在铂类化疗期间使用抗生素治疗与恶性肿瘤患者的预后不良有关。在本研究中，评估了粘膜抗生素暴露对铂类化疗后肾损伤的影响。基于临床转录组数据集的评估表明，在肾损伤期间，失调反应基因的水平升高，表明肠道和肾脏之间存在病理性通讯。实验中，在小鼠模型中，粘膜暴露于链霉素会加重铂诱导的肾小管损伤。此外，抗生素诱导的失调会增加对肠道粘膜炎症、上皮破坏和细菌暴露的易感性，从而对顺铂治疗产生反应。对腔微生物的进一步研究表明，抗生素诱导的失调促进了 物种的优势地位。此外，对失调微生物群落的功能评估预测了色氨酸代谢途径。特别是，失调反应性 与尿毒症毒素吲哚硫酸酯的产生和肾损伤有关。本研究包括基于细菌群落的评估结果，为器官间通讯和对抗与失调相关的疾病提供了新的预测见解。
