The oral microbiome is one of the most complex microbial ecosystems in the human body, and its balance is closely associated with oral and systemic health. Disruption of this balance can promote dental caries and periodontal disease, and conventional antibiotic-based control raises concerns about resistance and safety in special populations, which has motivated interest in food-derived compounds with selective antibacterial potential.
DHA, a polyunsaturated fatty acid, showed species- and strain-dependent selective inhibitory effects in single-species, mixed-species and human mouth-rinse interventions, modulating specific bacteria while maintaining the stability of oral microbiota.
A research team led by Jinfeng Wang at China Agricultural University evaluated four PUFAs against five common oral bacteria, in single-species and mixed-species cultures, and conducted an 8-day randomized, placebo-controlled human mouth-rinse intervention, analyzing saliva by metagenomic sequencing and qPCR.
At the strain level, the team isolated oral bacteria from saliva and compared DHA sensitivity among Fusobacterium pseudoperiodonticum isolates, followed by whole-genome analysis. The study aimed to evaluate the inhibitory effects of PUFAs on oral microorganisms and to elucidate the response patterns of the oral microbiota to DHA treatment and the genomic features associated with sensitivity or tolerance.
The team published their study in Acta Microbiologica Sinica on September 30, 2026.
Inhibitory effects
“The inhibitory effects of PUFAs on oral pathogens exhibit species- and system-dependent heterogeneity,” the authors write. In single-species cultures, S. oralis, S. mutans and P. gingivalis were relatively sensitive, whereas F. nucleatum and P. intermedia showed tolerance. In mixed-species cultures, the overall antibacterial effect was reduced. In the human intervention, an 8-day DHA mouth rinse did not significantly alter the oral microbiota at the phylum level, but selectively modulated the microbiota at the genus and species levels, with increased relative abundance of Neisseria and Porphyromonas and decreased relative abundance of Prevotella. Dynamic monitoring showed 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, such as lapB, pilE and ftsZ. Metagenomic data from saliva further supported a potential link between tolerance-associated genes and DHA tolerance.
Selective suppression
“DHA selectively suppresses specific bacteria while maintaining the overall stability of the oral microbiota,” said Jinfeng Wang, an author of the study at the College of Food Science & Nutritional Engineering, China Agricultural University. The authors suggest that DHA’s effects are not simple broad-spectrum killing but reflect differential responses among species and strains, plus ecological interactions within microbial communities. This milder, selective modulation could help maintain community stability and may support potential applications in oral microbiome regulation.
The authors caution that the human study was short and small, metagenomic samples were pooled, and the mixed-culture model is simplified. Future work should test longer interventions, include more oral species and validate gene functions.
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Other contributors include Sihan Li, Jiaqi Yang, Tian Tang, Qiuhan Cheng, Run Wang and Huimin Fan from the College of Food Science & Nutritional Engineering at China Agricultural University.
This work was supported by the National Natural Science Foundation of China (T2341010), the Pinduoduo-China Agricultural University Research Fund (PC2023B02015), and the 2115 Talent Development Program of China Agricultural University.
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