Intestinal is associated with functional, morphological, and molecular alterations in the cochlea.
Increased oxidative stress and inflammation occur in the cochlea due to gut microbiota disturbances.
Altered permeability of the blood-labyrinth barrier is linked to intestinal inflammation.
Macrophage infiltration and immune response activation are observed through a specific signaling pathway.
from patients with active ulcerative colitis worsens cochlear function.
Conversely, fecal microbiota transplantation from patients in remission shows a protective effect on hearing sensitivity.
Simplified
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 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 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.
Key numbers
20–25 dB
Increase in Auditory Thresholds
Auditory thresholds increased in ABX + mice compared to baseline.
Lower percentage of survival
Cochlear Hair Cell Survival
survival was significantly decreased in compared to other groups.
Higher DAI score in and groups
(DAI)
DAI scores indicated more severe colitis in than in .
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Declarations. Ethics approval and consent to participate: All the experiments were approved by the local ethical committee and the Italian Ministry of Health. All animal procedures were conducted in accordance with the guidelines of our Institution and were approved by the ethical committee (n° 436/2017-PR, prot. 1F295.35.EXT.66). All efforts were made to reduce the number of animals and minimize their suffering in accordance with the European Community Council Directive of November 24, 1986(86/609/EEC). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
