Inorganic nitrate: A potential prebiotic for oral microbiota dysbiosis associated with type 2 diabetes

Oral microbiota dysbiosis, concomitant with decreased abundance of nitrate (NO₃^-)-reducing bacteria, oral net nitrite (NO₂^-) production, and reduced nitric oxide (·NO) bioactivity, is associated with the development of cardiometabolic disorders. Therefore, restoring the oral microbiome to a health-associated state is suggested as a therapeutic approach to potentiate the NO₃^--NO₂^--·NO pathway and provide a backup resource for insufficient NO production in conditions including cardiovascular disease and type 2 diabetes mellitus (T2DM). The current review discusses how inorganic NO₃^- can improve the oral microbial community in patients with T2DM and act as a prebiotic. Both animal and human experiments indicated that inorganic NO₃^- modulates the oral microbiome by increasing the abundance of health-associated NO₃^--reducing bacteria (e.g., Neisseria and Rothia) and decreasing the plenty of species Prevotella and Veillonella, leading to oral NO₂^- accumulation and improved systemic ·NO availability. Supplementation with NO₃^- reduces caries- and periodontitis-associated bacteria and the pathogenic genus related to insulin resistance and glucose intolerance. In addition, inorganic NO₃^- may provide a more optimal environment for NO₃^- reductase activity in the oral cavity, as it increases salivary flow rate and prevents decreased pH by inhibiting acid-producing bacteria.