Butyrate enhances recovery of chemotherapy-induced oral mucositis by enhancing tight junction protein expression and inhibiting inflammatory responses.

Chemotherapy-induced oral mucositis (OM) is a common complication of cancer treatment that significantly impacts patients' quality of life. Butyrate, a short-chain fatty acid, has been shown to inhibit inflammation and mitigate intestinal mucosal damage. How, its effect in treating OM remains unclear. OM model in mice pretreated with 5-FU solution was established by injecting 20% acetic acid into oral mucosa. Sodium butyrate was given for treatment. H&E staining was used to observe histopathological changes, and qRT-PCR to assess inflammatory factor level changes in ulcer tissues after treatment. Also, qRT-PCR and immunofluorescence staining were used to evaluate the expression and distribution of tight junction protein in ulcer tissues. Sodium butyrate treatment improved the weight loss in mice caused by OM and promoted the repair of oral mucosa in a time-dependent manner. In addition, sodium butyrate significantly inhibited the mRNA levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18) in the ulcer tissue. Moreover, sodium butyrate promoted the mRNA and protein expressions of tight junction protein-1 (ZO-1) and Claudin-1 in the epithelial cells of the ulcer tissue. Butyrate promotes OM healing by reducing inflammation and increasing the expression of tight junction proteins in ulcer tissues.