부산대학교 도서관

Clostridioides difficileinfection (CDI) is the leading cause of healthcare-acquired infections worldwide. Probiotics are widely recommended to prevent CDI and its recurrences. Akkermansia muciniphila, as a therapeutic symbiont colonizing the intestinal mucosal layer, is considered to be a promising next-generation probiotic. In this work, we assessed the inhibitory effects of A. muciniphilaMucT and its derivatives on cytotoxicity and inflammatory response induced by C. difficileRT001 in Caco-2 cells. The results obtained from SEM revealed that the morphology of UV-killed A. muciniphilaremained unchanged after UV inactivation. TEM analysis showed that A. muciniphila–isolated extracellular vesicles (EVs) were spherical and ranged from 50 to 200 nm in size. Toxigenic supernatant (Tox-S) of C. difficileRT001 (500 μg/ml) significantly (P<0.01) reduced the cell viability of Caco-2 cells. Caco-2 cells treated with live (MOI 10), UV-killed (MOI 10), cell-free supernatant (CFS, 106cfu/ml), and EVs (20 μg/ml) of A. muciniphilaexhibited over 90% viability in comparison to untreated control. The neutralized CFS preparation using A. muciniphilaand its derivatives could notably reduce the expression level of inflammatory markers. Additionally, A. muciniphilaand its derivatives modulated the production of IL-1β, TNF-α, and IL-10 in Tox-S stimulated Caco-2 cells. We demonstrated that A. muciniphilaand its derivatives can modulate changes in the gut barrier–related genes and inflammatory response caused by C. difficileTox-S in Caco-2 cells.