Transplantation of fecal microbiota from Age-related hearing loss patients compels inflammaging, age-related macrophage changes and hair cell degeneration in cochlea of young mice

Abstract To prove the clinical association of gut microbiota to Age-related hearing loss (ARHL) and to observe the inflammaging and age-related macrophage changes in cochlea after microbiota alteration. Here, we conducted two-step Mendelian randomization (MR) to prove the mediation effect of immune cell in the association of gut microbiota to ARHL. Next, we adopted the fecal microbiota transplantation (FMT) method to transplant the gut microbiota of ARHL patients and healthy elderly into young C57BL/6 mice (2 month). Mice transplanted with fecal microbiota from ARHL patients exhibited elevated hearing thresholds at 2, 4, 8, 16 24 and 32kHz compared with other groups. After transplantation, we observed increased permeability of capillaries at blood-labyrinth barrier (BLB) and activation of NLRP3 inflammasome at spiral ligament (SLi), which were indicative of disrupted inner ear homeostasis and formation of local inflammatory milieu. Neuroinflammation was observed at SGN with higher abundance of macrophages and degeneration of outer hair cells (OHCs) was observed at basal turn of basilar membrane (BM) accompanied by higher level of complementary system and morphological changes of macrophages. Our findings highlighted the association of age-related microbiota dysbiosis to ARHL, thereby elucidating the immune factor in the in pathogenesis of ARHL and further providing the intervention of lifestyle and environmental factors in modulating gut microbiome as potential preventive strategies for ARHL.