In recent years, it has been estimated that globally, approximately 230 million individuals suffer from chronic suppurative otitis media (CSOM), with a significant proportion experiencing hearing loss as a direct consequence (Onifade et al., 2025). Around 21 million people are affected by hearing loss attributed to CSOM, particularly in low- and middle-income countries where healthcare access is limited (Organization, 2004). Additionally, approximately 97.83 million children and adolescents under the age of 20 years were affected by hearing loss globally in 2021, resulting in approximately 3.91 million years lived with disability (Guo et al., 2024).

Current treatment strategies for CSOM primarily involve antibiotics, topical antimicrobial agents, and surgical interventions, such as tympanoplasty and mastoidectomy (Mittal et al., 2015). However, these approaches often have limited efficacy, especially in cases with biofilm formation and antibiotic resistance (Bhutta et al., 2024). Antibiotics, while effective in some cases, are limited by the emergence of multidrug-resistant pathogens. For instance, Pseudomonas aeruginosa and Staphylococcus aureus have developed resistance to commonly used antibiotics such as ciprofloxacin and amoxicillin, rendering these drugs less effective (Hernando-Amado et al., 2025). Additionally, the inappropriate use of antibiotics can lead to imbalances in the normal microbiota of the ear, potentially exacerbating the condition (García-Villada et al., 2024). Topical antimicrobial agents, such as ear drops containing antibiotics or antiseptics, have the advantage of directly targeting the infected area. However, the presence of ear canal stenosis or perforation can hinder the proper delivery of these agents to the middle ear (Vishwanath et al., 2012). Moreover, patient adherence to treatment regimens is often poor, leading to incomplete treatment and recurrent infections. Furthermore, some patients may experience hypersensitivity reactions to topical agents, limiting their use (Vishwanath et al., 2012). Surgical interventions, including tympanoplasty and mastoidectomy, are employed to remove infected tissue and restore middle ear function. However, these procedures are invasive and carry inherent risks such as infection, bleeding, and hearing loss (García-Villada et al., 2024). Therefore, it is of significance to highlight the need for novel therapeutic target.

In recent years, the role of inflammasomes in the pathogenesis of CSOM has gained considerable attention. Inflammasomes are multiprotein complexes that play a crucial role in the innate immune response by activating caspase-1, which in turn leads to the maturation and secretion of pro-inflammatory cytokines, such as IL-1β and IL-18 (Schiel et al., 2024). Dysregulation of inflammasome activation has been implicated in various inflammatory diseases (Schiel et al., 2024; Sharma and Kanneganti, 2021; Guo et al., 2015), including CSOM, where it contributes to the chronic inflammatory state and tissue damage. Targeting inflammasomes has emerged as a promising therapeutic strategy, as it can potentially reduce inflammation and improve clinical outcomes in patients with CSOM.

Furthermore, recent studies have highlighted the importance of N6-methyladenosine (m6A) RNA modifications in the regulation of gene expression, particularly in the context of inflammatory responses (Wang et al., 2022; Li et al., 2023). m6A modifications are the most prevalent internal modifications in eukaryotic mRNA and have been shown to influence the stability, translation, and splicing of target transcripts (Hou et al., 2021; An and Duan, 2022; Oerum et al., 2021). Emerging evidence suggests that m6A modifications of genes related to inflammasome components and their regulators may play a critical role in modulating the inflammatory response in various diseases (Liu et al., 2021; Li et al., 2023; Lan et al., 2022). Given the involvement of inflammasomes in CSOM, investigating the role of m6A modifications in the regulation of inflammasome-related genes could provide new insights into the pathogenesis of this condition and open up novel therapeutic avenues. Understanding the interplay between m6A modifications and inflammasome activation in CSOM may offer a more comprehensive approach to developing targeted therapies, thereby improving the management and outcomes of this debilitating disease.

In this study, CSOM model mice were established, the effective concentration of single-sided deafness (SSD) in alleviating serous otitis media (SOM) was investigated by evaluating bacterial load, cytokine levels and tissue morphology of middle ear. Whether the expression level of m6A modification related genes is regulated by SSD has also been further explored. We aimed to provide evidence that m6A related genes mediated by SSD may become new targets for the treatment of SOM in the future.