Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis
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. Me...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-025-02338-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342896375857152 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Anna Pisani |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-252d35a1e9c449a488202a726422cbcf |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-252d35a1e9c449a488202a726422cbcf2025-08-20T03:43:14ZengBMCCell Communication and Signaling1478-811X2025-07-0123112010.1186/s12964-025-02338-1Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axisAnna Pisani0Valentina Petito1Fabiola Paciello2Valeria Emoli3Letizia Masi4Veronica Mohamed Hizam5Pierluigi Puca6Raffaele Montuoro7Federica Del Chierico8Lorenza Putignani9Claudio Grassi10Jacopo Galli11Maurizio Taglialatela12Maria Emiliana Caristo13Gianluca Ianiro14Loris Riccardo Lopetuso15Giovanni Cammarota16Antonio Gasbarrini17Anna Rita Fetoni18Franco Scaldaferri19Dipartimento di Neuroscienze, Unità di Audiologia, Università degli Studi di Napoli Federico IICeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSDipartimento di Neuroscienze, Università Cattolica del Sacro CuoreCeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSCeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSDipartimento Testa-collo e organi di senso, Università Cattolica del Sacro CuoreCeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSDipartimento Testa-collo e organi di senso, Università Cattolica del Sacro CuoreUnità di Microbiomica e Microbioma Umano, Ospedale Pediatrico Bambino Gesù IRCCSImmunologia, Reumatologia e Malattie Infettive, Unità di microbioma umano, IRCCSDipartimento di Neuroscienze, Università Cattolica del Sacro CuoreFondazione Policlinico Universitario A. Gemelli IRCCSDipartimento di Neuroscienze, Unità di Audiologia, Università degli Studi di Napoli Federico IICen.Ri.S., Università Cattolica del Sacro CuoreCeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSCeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSDigestive Disease Center “CeMAD”, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario “A. Gemelli” IRCCSCeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSDipartimento di Neuroscienze, Unità di Audiologia, Università degli Studi di Napoli Federico IICeMAD Translational Research Laboratories Digestive Disease Center, Department of Medical and Surgical sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCSAbstract 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.https://doi.org/10.1186/s12964-025-02338-1CochleaGut dysbiosisGut microbiotaInflammation |
| spellingShingle | 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 Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis Cell Communication and Signaling Cochlea Gut dysbiosis Gut microbiota Inflammation |
| title | Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis |
| title_full | Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis |
| title_fullStr | Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis |
| title_full_unstemmed | Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis |
| title_short | Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis |
| title_sort | intestinal inflammation and microbiota modulation impact cochlear function emerging insights in gut ear axis |
| topic | Cochlea Gut dysbiosis Gut microbiota Inflammation |
| url | https://doi.org/10.1186/s12964-025-02338-1 |
| work_keys_str_mv | AT annapisani intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT valentinapetito intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT fabiolapaciello intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT valeriaemoli intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT letiziamasi intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT veronicamohamedhizam intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT pierluigipuca intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT raffaelemontuoro intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT federicadelchierico intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT lorenzaputignani intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT claudiograssi intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT jacopogalli intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT mauriziotaglialatela intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT mariaemilianacaristo intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT gianlucaianiro intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT lorisriccardolopetuso intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT giovannicammarota intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT antoniogasbarrini intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT annaritafetoni intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis AT francoscaldaferri intestinalinflammationandmicrobiotamodulationimpactcochlearfunctionemerginginsightsingutearaxis |