The gut-inflammation-hearing axis in diabetic patients aged 30–55: exploring microbiome-mediated pathways to auditory complications

Abstract

Abstract Background/Objectives Hearing impairment is an underrecognized yet prevalent complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms remain poorly understood. This study investigated whether gut microbiota dysbiosis contributes to diabetic hearing loss through systemic inflammatory pathways, and evaluated the potential of microbiota-inflammation biomarkers for early risk identification. Methods We conducted a cross-sectional study of 100 T2DM patients aged 30–55 years. Hearing function was assessed using pure-tone audiometry. Gut microbiota composition was analyzed by 16 S rRNA gene sequencing. Plasma inflammatory biomarkers including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), high-sensitivity C-reactive protein (hs-CRP), and lipopolysaccharide-binding protein (LBP) were measured by ELISA. Mediation analyses with bootstrapping (5,000 resamples) examined whether inflammatory markers mediated the relationship between gut dysbiosis and hearing impairment. Receiver operating characteristic curves evaluated biomarker discriminatory ability. Results Hearing impairment was present in 43% of participants. Patients with hearing impairment exhibited significant gut dysbiosis characterized by depletion of anti-inflammatory bacteria ( Faecalibacterium : 6.2% vs. 9.8%, P < 0.001; Roseburia ; Akkermansia ) and enrichment of pro-inflammatory taxa ( Escherichia-Shigella : 3.8% vs. 1.4%, P < 0.001; Klebsiella ; Desulfovibrio ). Inflammatory markers were significantly elevated, particularly LBP (18.6 vs. 12.4 µg/mL, P < 0.001), TNF-α (4.82 vs. 3.21 pg/mL, P < 0.001), and IL-6 (5.67 vs. 3.45 pg/mL, P < 0.001). Mediation analyses revealed that inflammatory pathways, predominantly through LBP-mediated gut barrier dysfunction, accounted for 48.7–56.3% of the total effect of microbiota alterations on hearing impairment (all P < 0.001). An integrated biomarker panel combining microbial taxa ( Faecalibacterium , Escherichia-Shigella , Shannon diversity) and LBP achieved excellent discrimination for identifying hearing impairment (AUC = 0.921, 95% CI: 0.869–0.973; sensitivity 88.4%, specificity 87.7%). Conclusions This study establishes a novel gut-inflammation-hearing axis in type 2 diabetes, wherein microbiota dysbiosis characterized by loss of beneficial bacteria and expansion of pathogenic taxa promotes hearing impairment through systemic inflammation mediated by intestinal barrier dysfunction and metabolic endotoxemia. These findings identify gut barrier integrity and associated inflammatory pathways as potential therapeutic targets, and demonstrate that integrated microbiota-inflammation biomarker panels can serve as non-invasive tools for early identification of hearing impairment risk in diabetic patients, enabling targeted preventive interventions.