competition with strains impairs potentially pathogenic growth of on 2'-fucosyllactose.

Fortifying infant formula with human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), is a global trend. Previous studies have shown the inability of pathogenic gut microbes to utilize 2'-FL. However, the present study demonstrates that the type strain (JCM 1290) of , a pathobiont species often more prevalent and abundant in the feces of C-section-delivered infants, exhibits potentially pathogenic growth on 2'-FL. The expression of genes for α-toxin, an activator of NLRP3 inflammasome, and ethanolamine ammonia-lyase, a factor responsible for the progression of gas gangrene, was significantly upregulated during 2'-FL assimilation compared to growth on lactose. However, colony-forming unit of JCM 1290 markedly decreased when co-cultivated with selected strains of , a taxon frequently detected in the breastfed infant gut. Moreover, during co-cultivation, the expression of virulence-related genes, including the gene for perfringolysin O - another activator of NLRP3 inflammasome - were significantly downregulated, while the lactate oxidation genes were upregulated. This can occur through two different mechanisms: direct competition for 2'-FL between the two organisms, or cross-feeding of lactose, released from 2'-FL by JCM 1290, to . Attenuation of α-toxin production by the selected strains was observed to varying extents in 2'-FL-utilizing strains clinically isolated from healthy infants. Our results warrant detailed studies using animal models with dysbiotic microbiota dominated by various types of strains to further validate the safety of 2'-FL for clinical interventions, particularly on vulnerable preterm infants.