Improved gut microbiota by selenium-enriched Bifidobacterium longum DD98 alleviates chemotherapy-induced intestinal mucositis via inhibiting the STING pathway

Intestinal mucositis, a common chemotherapy side effect, lacks effective treatments. This study evaluated the protective effect of selenium-enriched Bifidobacterium longum DD98 (SeDD98) on irinotecan-induced intestinal mucositis. Irinotecan caused intestinal mucositis, characterized by weight loss, severe diarrhea, damaged intestinal structure, reduced tight junction proteins, and gut dysbiosis. These effects could be inhibited by SeDD98. Additionally, fecal microbiota from SeDD98-treated mice protected against intestinal mucositis. Mechanistically, irinotecan activated the stimulator of interferon genes (STING) / nuclear factor kappa-B (NF-κB) pathway, whereas SeDD98 and fecal microbiota from SeDD98-treated mice suppressed this activation. Furthermore, depletion of gut microbiota by a broad-spectrum antibiotic cocktail (ABX) blunted the protective effect of SeDD98 and its inhibition of the STING/NF-κB pathway. These findings suggest that SeDD98 could protect against intestinal mucositis via inhibiting the STING/NF-κB pathway, likely through improving gut microbiota. Overall, SeDD98 may be a potential therapeutic agent for preventing chemotherapy-induced intestinal mucositis via gut microbiome improvement.