Mao Shuangshuang, Zhang Zirui, Huang Mao, Zhang Ziying, Hong Yu, Tan Xiaohua, Gui Fei, Cao Yifei, Lian Fuzhi, Chen Rong
School of Public Health, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
Ji'an County People's Hospital, Jiangxi, 343100, China.
Sci Rep. 2025 Mar 19;15(1):9434. doi: 10.1038/s41598-025-90655-3.
Sensorineural hearing loss (SNHL) poses a significant global health challenge with substantial socioeconomic and medical implications. The pathophysiology involves excessive reactive oxygen species (ROS) in the cochlea, inflammation, cellular apoptosis, etc. Tryptophan metabolite indole-3-propionic Acid (IPA), produced by gut microbiota, may offer therapeutic benefits by modulating inflammation, oxidative stress, and immune responses. However, the roles of IPA in protecting from treatment hearing loss in adult mice remain to be investigated. We previously validated that exposure to pesticide metabolite 3, 5, 6-Trichloro-2-pyridinol (TCP) caused hearing loss in mice. Herein, continuous administration of 40 mg/kg IPA for 21 days significantly attenuated the hearing threshold elevation in C57BL/6 mice exposed to 50 mg/kg TCP. IPA treatment reduced the loss of hair cells (HCs) and spiral ganglion neurons (SGNs), preserved nerve fibers, and reversed the damage to spiral ligaments (SL) and stria vascularis (SV). Similarly, IPA cotreatment decreased ROS accumulation in the cochlea and inhibited HC and SGN apoptosis. Transcriptomic analysis showed that IPA enhanced immune responses, particularly through neutrophil recruitment and the activation of regenerative signals like IFNγ. These findings underscore IPA's protective effects against TCP-induced hearing loss, highlighting the role of immune mechanisms in cochlear protection.
感音神经性听力损失（SNHL）是一项重大的全球健康挑战，具有重大的社会经济和医学影响。其病理生理学涉及耳蜗中过量的活性氧（ROS）、炎症、细胞凋亡等。由肠道微生物群产生的色氨酸代谢物吲哚-3-丙酸（IPA）可能通过调节炎症、氧化应激和免疫反应提供治疗益处。然而，IPA在保护成年小鼠免受治疗性听力损失方面的作用仍有待研究。我们之前证实，接触农药代谢物3,5,6-三氯-2-吡啶醇（TCP）会导致小鼠听力损失。在此，对暴露于50mg/kg TCP的C57BL/6小鼠连续21天给予40mg/kg IPA可显著减轻听力阈值升高。IPA治疗减少了毛细胞（HCs）和螺旋神经节神经元（SGNs）的损失，保留了神经纤维，并逆转了对螺旋韧带（SL）和血管纹（SV）的损伤。同样，IPA联合治疗减少了耳蜗中的ROS积累，并抑制了HC和SGN凋亡。转录组分析表明，IPA增强了免疫反应，特别是通过中性粒细胞募集和激活IFNγ等再生信号。这些发现强调了IPA对TCP诱导的听力损失的保护作用，突出了免疫机制在耳蜗保护中的作用。
