Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-07-26 DOI:10.1186/s12964-025-02338-1

Anna Pisani, Valentina Petito, Fabiola Paciello, Valeria Emoli, Letizia Masi, Veronica Mohamed Hizam, Pierluigi Puca, Raffaele Montuoro, Federica Del Chierico, Lorenza Putignani, Claudio Grassi, Jacopo Galli, Maurizio Taglialatela, Maria Emiliana Caristo, Gianluca Ianiro, Loris Riccardo Lopetuso, Giovanni Cammarota, Antonio Gasbarrini, Anna Rita Fetoni, Franco Scaldaferri

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引用次数: 0

Abstract

Background: Although several evidence demonstrates a "gut-microbiota-brain axis", suggesting a bidirectional communication between gut microbiota and the central nervous system, less is known about a possible link between the gut and the peripheral nervous system, including the inner ear.

Methods: Here, we investigated the impact of intestinal inflammation and the modulation of gut microbiota through fecal microbiota transplantation on hearing sensitivity. Female C57BL/6 mice were assigned to four groups: control (Ctrl), DSS-induced colitis (DSS), FMT from patients with active ulcerative colitis (FMT aUC), and FMT from patients with ulcerative colitis in remission (FMT rUC). Auditory function was evaluated by auditory brainstem responses (ABR). Morphological and molecular analyses on cochlear tissues were performed using immunofluorescence, histological staining, and Western blot to assess inflammation, oxidative stress, and blood-labyrinth barrier integrity. Donor microbiota composition was characterized by 16S rRNA sequencing, and systemic inflammation was evaluated by measuring serum lipopolysaccharide (LPS) levels.

Results: We found that intestinal dysbiosis is associated with functional, morphological, and molecular alterations in the cochlea, such as increased oxidative stress, inflammation, and altered blood-labyrinth barrier permeability. This leads to macrophage infiltration and immune response activation through the MyD88/NF-κB pathway. Notably, these effects were exacerbated by FMT from subjects with aUC, while FMT from patients with rUC provided a protective effect on cochlear functions.

Conclusions: Overall, our findings suggest that gut inflammation, microbiota alteration, or its therapeutic modulation can impact inner ear pathology: worsening gut inflammatory status negatively affects hearing sensitivity, while the restoration of gut microbiota positively impacts auditory function.

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肠道炎症和微生物群调节影响耳蜗功能：肠-耳轴的新见解。

背景：尽管一些证据表明存在“肠道-微生物群-脑轴”，表明肠道微生物群与中枢神经系统之间存在双向交流，但肠道与周围神经系统（包括内耳）之间可能存在的联系尚不清楚。方法：本研究通过粪便菌群移植研究肠道炎症和肠道菌群调节对听力敏感性的影响。雌性C57BL/6小鼠分为4组：对照组（Ctrl）、DSS性结肠炎（DSS）、活动期溃疡性结肠炎患者FMT （FMT aUC）和缓解期溃疡性结肠炎患者FMT （FMT rUC）。用听觉脑干反应（ABR）评价听觉功能。使用免疫荧光、组织学染色和Western blot对耳蜗组织进行形态学和分子分析，以评估炎症、氧化应激和血迷宫屏障的完整性。通过16S rRNA测序鉴定供体微生物群组成，通过测定血清脂多糖（LPS）水平评估全身炎症。结果：我们发现肠道生态失调与耳蜗的功能、形态和分子改变有关，如氧化应激增加、炎症和血迷宫屏障通透性改变。通过MyD88/NF-κB通路导致巨噬细胞浸润和免疫应答激活。值得注意的是，来自aUC受试者的FMT加剧了这些影响，而来自rUC患者的FMT对耳蜗功能具有保护作用。结论：总体而言，我们的研究结果表明，肠道炎症、微生物群的改变或其治疗调节可以影响内耳病理：肠道炎症状态的恶化对听力敏感性产生负面影响，而肠道微生物群的恢复对听觉功能产生积极影响。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.