journal article·2026-03Open access

Gut–Metabolome–Proteome Interactions in Age‐Related Hearing Loss: Insights from Fecal Microbiota Transplantation and Multi‐Omics Analyses

Ting Yang, Ziwen Gao, Hui Huang, Chanyuan Zhang, Yiquan Tang, Qianhui Qu, Huabin Li, Jing Ke, Zhiji Chen, Menglong Feng, Hu Zhou, Yilai Shu, Wei Yuan

Advanced Science· Volume 13· Issue 18

Abstract

ABSTRACT Age‐related hearing loss (ARHL) is a prevalent sensory disorder lacking disease‐modifying interventions. The biological drivers, particularly the contribution of the gut microbiota and gut–inner ear crosstalk, remain poorly defined. Here, we utilize germ‐free (GF) mice and fecal microbiota transplantation (FMT) to isolate microbiota‐dependent effects on ARHL progression. Through integrated metagenomic, metabolomic, and proteomic profiling, we map molecular signatures of auditory aging and uncover functional gut‐inner ear network, prioritizing 5‐hydroxytryptophan (5‐HTP) as a key intermediate metabolite within this network. Furthermore, in an aging‐like House Ear Institute–Organ of Corti 1 (HEI‐OC1) model, 5‐HTP exhibits protective effects, potentially mediated through the PI3K/Akt–antioxidant signaling axis. Collectively, this study provides a valuable multi‐omics resource and highlights microbiota‐derived metabolic regulation as a promising avenue for biomarker discovery and therapeutic development in ARHL.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Hearing, Cochlea, Tinnitus, Genetics · Gut microbiota and health · Vestibular and auditory disorders

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Otorhinolaryngology Head and Neck Surgery Chongqing General Hospital Chongqing University Chongqing China

ENT Institute and Department of Otorhinolaryngology Eye and ENT Hospital Fudan University Shanghai China

Institutes of Biomedical Science Fudan University Shanghai China

NHC Key Laboratory of Hearing Medicine Shanghai China

State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University Shanghai China

School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China

Department of Analytical Chemistry State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China

Institutes of Biomedical Sciences Shanghai Key Laboratory of Medical Epigenetics International Co‐laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Department of Systems Biology for Medicine Fudan University Shanghai China

Funding

National Natural Science Foundation of China

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