Nitrate sustains oral microbiome function and gastric NO synthesis during antiseptic use

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Graphical abstract Abstract Objective The nitrate–nitrite–•NO pathway is a fundamental source of gastric nitric oxide (•NO), yet it is highly susceptible to disruption by antiseptic mouthwashes. This study investigated whether dietary nitrate supplementation could mitigate the functional impact of chlorhexidine (CHX)-induced oral dysbiosis and preserve downstream gastric •NO synthesis. Methods In a randomized pilot study, 15 healthy volunteers were assigned to three groups of 7-day treatment: i) CHX mouthwash (n = 5), ii) nitrate-rich beetroot juice (n = 6), or iii) CHX + nitrate (n = 4). Salivary nitrate reductase activity, •NO concentration in the gastric headspace, and systemic markers (serum nitrate and nitrite, blood pressure, and inflammatory markers) were assessed at baseline (D0) and day 7 (D7). Results CHX alone induced an ∼78% decrease in microbial nitrate reductase activity and a 77-fold reduction in gastric •NO synthesis. Conversely, concurrent nitrate supplementation attenuated these effects, limiting the loss of microbial activity to ∼57% and the drop in gastric •NO by an order of magnitude. While systemic blood pressure and inflammatory markers (CRP and fecal calprotectin) remained unchanged in this healthy cohort, salivary pH and buffering capacity showed a trend toward improvement with nitrate supplementation. Conclusion Oral dysbiosis induced by the antiseptic chlorhexidine significantly impairs the bioactivation of nitrate, hindering gastric synthesis of •NO and downstream •NO-dependent signaling. Moreover, dietary nitrate supplementation mitigated these collateral effects associated with the use of oral antiseptic solutions by partially preserving microbial function and sustaining gastric •NO production. Significance statement These findings suggest that increasing dietary nitrate intake may serve as a protective strategy to counteract the collateral suppression of the nitrate–nitrite–•NO pathway during clinical use of oral antiseptics.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.