Abstract
CONTEXT: Fluoride can prevent dental caries by inhibiting demineralization and promoting remineralization of teeth while affecting the physiology of oral microbiota, thus inhibiting cellular enzymes. However, the effect of systemic fluoride on gut microbiota is unknown. OBJECTIVE: To explore the impacts of systemic fluoride on gut microbiota composition and abundance and associated functions such as gene and metabolic regulation. DATA SOURCES: A systematic database search was conducted of MEDLINE, Web of Science, Scopus, PubMed, CINAHL, and Embase to find articles on studies reporting the effects of fluoride on gut microbiota. DATA EXTRACTION: Forty-nine studies were included (n = 42 in animals, 4 of humans, 3 in vitro studies) after screening for title, abstract, and full text using Covidence to check against eligibility criteria. Data were extracted using Covidence and study quality was assessed using the Mixed Method Appraisal Tool by 2 reviewers independently. DATA ANALYSIS: Two human studies of dental fluorosis and 1 of patients with breast cancer (intestinal fluorine-18 fluorodeoxyglucose uptake) showed significant differences in gut microbial composition, with increased relative abundance of Acidobacteria and Proteobacteria, and decreased abundance of Firmicutes and Bacteroidetes. An ex vivo study of human feces indicated that ≤ 2 mg L-1 NaF might boost "health-associated" taxa, but concentrations (≥ 10 mg L-1 NaF) could increase the ratio of some unhealthy microbes after 24 hours. The animal studies examined the effects of high fluoride doses in water and diet (50-1200 mg L-1 NaF) for long-term (1-6 months) and short-term (6 hours to 7 days) exposure, with all showing a significant disturbance in the Firmicutes to Bacteroidota ratio. CONCLUSION: In humans, high doses potentially may be detrimental to the microbiome, whereas ≤ 2 mg L-1 NaF had positive effects. Similarly, in animals, ≥ 50 mg L-1 NaF was unsafe, whereas ≤ 25 mg L-1 NaF had harmless effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42022347357.