BACKGROUND:The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). METHODS: Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. RESULTS: Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4 + T cells (76.59% vs 52.85%; P < .05), CD8 + T cells (62.94% vs 29.76%; P < .05), and CD3 + T cells (69.72% vs 45.49%; P < .05) in an A-CCRT-P (after treatment with radiotherapy plus chemotherapy plus the probiotic combination) group. Highthroughput sequencing results indicated that CCRT had obviously disturbed the intestinal diversity of patients in an A-CCRT (after treatment with radiotherapy plus chemotherapy plus a placebo) group, whereas the probiotic combination distinctly restored the microbial diversity in the A-CCRT-P group toward that of healthy people and a B-CCRT-P (before the treatment of radiotherapy plus chemotherapy plus the probiotic combination) group. CONCLUSIONS: A probiotic combination significantly enhances the immune response of patients and reduces the severity of OM through modification of gut microbiota.

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Earlier evidence has proven that probiotic supplements can reduce concurrent chemoradiotherapy (CCRT)-induced oral mucositis (OM) in nasopharyngeal cancer (NPC). The incidence of severe OM (grade 3 or higher) was the primary endpoint in this study. We first enrolled 85 patients with locally advanced NPC who were undergoing CCRT. Of them, 77 patients were finally selected and randomized (1:1) to receive either a probiotic cocktail or placebo. To investigate the protective effects and the mechanism of probiotic cocktail treatment on OM induced by radiotherapy and chemotherapy, we randomly divided the rats into the control (C) group, the model (M) group, and the probiotic (P) group. After treatment, samples from the tongue, blood, and fecal and proximal colon tissues on various days (7th, 14th, and 21st days) were collected and tested for the inflammatory response, cell apoptosis, intestinal permeability, and intestinal microbial changes. We found that patients taking the probiotic cocktail showed significantly lower OM. The values of the incidence of 0, 1, 2, 3, and 4 grades of OM in the placebo group and in the probiotic cocktail group were reported to be 0, 14.7, 38.2, 32.4, and 14.7% and 13.9, 36.1, 25, 22.2, and 2.8%, respectively. Furthermore, patients in the probiotic cocktail group showed a decrease in the reduction rate of CD3+ T cells (75.5% vs. 81%, p &lt; 0.01), CD4+ T cells (64.53% vs. 79.53%, p &lt; 0.01), and CD8+ T cells (75.59 vs. 62.36%, p &lt; 0.01) compared to the placebo group. In the rat model, the probiotic cocktail could ameliorate the severity of OM, decrease the inflammatory response, cause cell apoptosis and intestinal permeability, and restore the structure of gut microbiota to normalcy. In conclusion, the modified probiotic cocktail significantly reduces the severity of OM by enhancing the immune response of patients with NPC and modifying the structure of gut microbiota.Clinical Trial Registration: The Clinical Trial Registration should be the NCT03112837.