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[Objective] To evaluate the inhibitory effects of polyunsaturated fatty acids (PUFAs) on oral microorganisms and to elucidate the response patterns of the oral microbiota to docosahexaenoic acid (DHA) treatment, as well as the genomic features associated with the sensitivity or tolerance. [Methods] The minimum inhibitory concentrations of four PUFAs were determined for five common species of oral bacteria. The effects of PUFAs at different concentrations on planktonic growth and biofilm formation were assessed in both single-species and mixed-species culture systems. Human intervention and metagenomic sequencing were employed to analyze the impact of DHA on oral microbiota composition and the abundance of specific bacterial taxa. The DHA sensitivity of Fusobacterium pseudoperiodonticum isolates from saliva was compared, followed by whole-genome analysis. [Results] The inhibitory effects of the four PUFAs varied among bacterial species. In single-species cultures, Streptococcus oralis, Streptococcus mutans, and Porphyromonas gingivalis were sensitive, whereas Fusobacterium nucleatum and Prevotella intermedia showed tolerance. In mixed-species cultures, the overall antibacterial effects were reduced. In the human intervention study, an 8-day mouth rinse with DHA did not significantly alter oral microbiota at the phylum level, while selectively modulating the oral microbiota at the genus and species levels, with increased relative abundance of Neisseria and Porphyromonas and decreased relative abundance of Prevotella. Dynamic monitoring indicated that DHA selectively influenced certain taxa over time, inducing a downward trend in F. nucleatum abundance. Strain-level analysis revealed differential DHA sensitivity among F. pseudoperiodonticum isolates, which was closely associated with variations in genes related to cell envelope and lipid metabolism (e.g., lapB, pilE, and ftsZ). [Conclusion] The inhibitory effects of PUFAs on oral pathogens exhibit species- and system-dependent heterogeneity. DHA selectively suppresses specific bacteria while maintaining the overall stability of the oral microbiota, and the strain-dependent variation in sensitivity may be associated with genomic characteristics. These findings provide new evidence for understanding the role of PUFAs, particularly DHA, in oral microbiota modulation and support their potential applications in this field.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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