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Probiotics Exert Colonization Resistance Against F. nucleatum subsp. polymorphum: Disruption by Antibiotics and
Wenling Huang1,2, Jingheng Liang1,2, Poukei Chan1,2
1Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Abstract:
Fusobacterium nucleatum (F. nucleatum), a key oral pathogen, promotes colorectal cancer (CRC) progression via gut translocation. Although gut probiotics provide colonization resistance against pathogens, antibiotic-induced dysbiosis may facilitate F. nucleatum integration and increase the risk of CRC. The mechanisms underlying probiotic-F. nucleatum antagonism and antibiotic modulation remain unclear. A 33-strain probiotic consortium and F. nucleatum subsp. Polymorphum (F. polymorphum) ATCC 10953 were co-cultured. The inhibitory effects of probiotics on F. nucleatum and the impacts of antibiotics (ABXs) on the microbial community structure in the co-culture system and on the probiotic-mediated inhibition of F. nucleatum were evaluated using spent medium assays, plate confrontation tests, growth curves, qRT-PCR, metagenomic sequencing, and transcriptomics. Hydrogen peroxide/pH/lysine assays and coaggregation models were performed to probe the associated mechanisms. Probiotics strongly inhibited the growth of F. nucleatum in a dose-dependent manner, primarily via organic acids, while F. nucleatum enriched amino acid/vitamin biosynthesis pathways without major growth suppression. Antibiotics weakened probiotic antagonism, shifted species abundance (↓ L. plantarum, ↑ L. paracasei), induced adaptive stress responses in F. nucleatum (↑ nucleotide metabolism, propanediol degradation, pdxS), and reduced lysine biosynthesis. Lysine supplementation restored probiotic abundance and disrupted F. nucleatum coaggregation. Multi-strain probiotics exert potent colonization resistance effects against F. nucleatum, mainly through organic acids and metabolic interference. Antibiotic-induced dysbiosis impairs this protective effect and may promote the persistence of F. nucleatum, which has been implicated in CRC risk. Targeted probiotic strategies may offer novel preventive approaches.
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