Response to the Letter to the Editor: “Carcinogenesis of Male Oral Submucous Fibrosis Alters Salivary Microbiomes”

Abstract

In their Letter to the Editor, Sarode et al. (2021) mentioned that decreased salivary secretion is a symptom of oral submucous fibrosis (OSF) and that the salivary microbiome alteration observed in our study might be attributed to xerostomia in patients with OSF. They suggested assessing salivary flow rate, iron deficiency anemia, and immune status in patients with OSF and healthy controls to make our conclusions more robust. We appreciate these comments and suggestions regarding our work. Changes in the oral microenvironment due to age, diet, lifestyle (e.g., consumption of alcohol, cigarettes, or betel nut), and disease progression may alter the oral microbiome (Healy and Moran 2019; Kakabadze et al. 2020). The oral microbiome could also be affected by xerostomia (Rusthen et al. 2019). Among Taiwanese men, OSF is mainly caused by betel nut chewing; the reported incidence of xerostomia in patients with OSF ranges from 54.5% to 72.2%, and it is significantly and negatively associated with maximal mouth opening. The incidence of xerostomia was significantly higher in patients with OSF than in betel nut chewers without OSF (Tai et al. 2001;Chiu et al. 2002). However, our study focused on the salivary microbiome in male patients with OSF and patients with oral squamous cell carcinoma (OSCC) who also had background OSF. We were unaware of a difference in xerostomia complaints between the 2 cohorts, although it must be noted that we did not collect these data. This study also excluded patients receiving radiotherapy, which can cause xerostomia. Studies have revealed that before undergoing radiotherapy and chemotherapy, patients with OSCC have unstimulated salivary flow rates (0.3 to 0.35 mL/min; Epstein et al. 1998;Lal et al. 2010) that are similar to those of healthy individuals (0.3 to 0.4 mL/ min; Iorgulescu 2009). We believe that comparing salivary flow rates between these patients and healthy controls will enhance our understanding of the changes in the oral microbiome that are associated with OSF-induced changes in health. However, this was not the objective of our study. Zhong et al. (2020) recently reported on alterations in the oral microbiome due to OSF; they observed that the diversity of the microbial community in the gingiva (but not in the buccal mucosa or dorsum) was highest in healthy betel nut chewers, followed by patients with OSF and those with OSCC. Nevertheless, we agree that a comprehensive characterization of the host status, including inflammation and immune response, aids studies of the microbiome-host interplay.