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

• Published in: Cell communication and signaling Vol. 23; no. 1; pp. 357 - 20
• Main Authors: Pisani, Anna, Petito, Valentina, Paciello, Fabiola, Emoli, Valeria, Masi, Letizia, Hizam, Veronica Mohamed, Puca, Pierluigi, Montuoro, Raffaele, Chierico, Federica Del, Putignani, Lorenza, Grassi, Claudio, Galli, Jacopo, Taglialatela, Maurizio, Caristo, Maria Emiliana, Ianiro, Gianluca, Lopetuso, Loris Riccardo, Cammarota, Giovanni, Gasbarrini, Antonio, Fetoni, Anna Rita, Scaldaferri, Franco
• Format: Journal Article
• Language: English
• Published: London BioMed Central 26.07.2025; BioMed Central Ltd; BMC
• Subjects: Animals; Antibiotics; Auditory system; Bacteria; Biomedical and Life Sciences; Brain stem; Cell Biology; Central nervous system; Cochlea; Cochlea - pathology; Cochlea - physiopathology; Colitis, Ulcerative - microbiology; Colorectal diseases; Complications and side effects; Cytokines; Cytokines and Growth Factors; Development and progression; Digestive system; Disease; Dysbacteriosis; Dysbiosis; Fecal Microbiota Transplantation; Fecal microflora; Feces; Female; Gastrointestinal diseases; Gastrointestinal Microbiome; Gastrointestinal tract; Gut dysbiosis; Gut microbiota; Health aspects; Hearing; Hearing disorders; Hearing loss; Hearing protection; Humans; Immune response; Immune system; Immunofluorescence; Inflammation; Inflammation - pathology; Inflammatory bowel disease; Inflammatory bowel diseases; Inner ear; Intestinal microflora; Intestine; Intestines - microbiology; Intestines - pathology; Life Sciences; Lipopolysaccharides; Macrophages; Metabolism; Mice; Mice, Inbred C57BL; Microbiota; Microbiota (Symbiotic organisms); MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Nervous system; Neurodegeneration; NF-κB protein; Oxidative stress; Pathogens; Permeability; Protein-Ligand Interactions; Receptors; Remission; Remission (Medicine); Risk factors; rRNA 16S; Ulcerative colitis; Italy; Gut microbiota; Cochlea; Gut dysbiosis; Inflammation
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-025-02338-1

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. Plain English summary While the gut-brain axis has been widely studied, less is known about the potential connection between gut health and structures of the peripheral nervous system, such as the inner ear. In this study, we examined whether gut inflammation and changes in gut bacteria (microbiota) can impact hearing. We used a mouse model to mimic intestinal inflammation by administering a chemical (DSS) that induces colitis. Some mice also received fecal microbiota transplantation (FMT), a procedure in which gut bacteria from patients with ulcerative colitis (UC) were transferred into the mice. We tested two types of FMT: one from patients with active UC (severe inflammation) and another from patients with quiescent UC. Our results showed that intestinal inflammation negatively affects hearing by causing damage to the inner ear. Mice with colitis exhibited increased inflammation, oxidative stress, and weakening of the blood-labyrinth barrier, a structure that normally protects the ear. Mice that received FMT from patients with active UC experienced even more severe hearing impairment and inner ear damage. Conversely, those that received FMT from patients with quiescent UC showed reduced damage and better hearing, suggesting that a healthier gut microbiota may have a protective effect on the auditory system. These findings suggest that gut health and microbiota composition can influence hearing. While severe gut dysbiosis worsens cochlear damage, microbiota modulation through FMT may offer protective effects. This highlights the potential of microbiota-based therapies to prevent hearing loss, particularly in individuals with inflammatory bowel disease.