A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma

Randomized, double-blind, placebo-controlled trial in male and female patients aged 18-70 with locally advanced nasopharyngeal cancer undergoing concurrent chemoradiotherapy (cisplatin + IMRT). Enrolled 85; randomized 77 (probiotic n=39; placebo n=38); final analyzed: 36 probiotic, 34 placebo. Ethics approval; informed consent; trial registered NCT03112837.

Oral probiotic capsule mixture containing Lactobacillus plantarum MH-301 (10^9 CFU), Bifidobacterium animalis subsp. lactis LPL-RH (10^9 CFU), Lactobacillus rhamnosus LGG-18 (10^9 CFU), and Lactobacillus acidophilus (10^9 CFU); 1 capsule, taken twice daily for 7 weeks starting on the first day of chemoradiotherapy.

Probiotic cocktail significantly reduced OM severity during CCRT in NPC. OM grades 0–4: placebo 0/14.7/38.2/32.4/14.7% vs probiotic 13.9/36.1/25/22.2/2.8% (p<0.01). Grade 3–4 OM decreased from 47.1% (placebo) to 25% (probiotic); grade 4 OM from 14.7% to 2.8%. Immune measures showed smaller reductions in CD3+ T cells (75.5% vs 81%, p<0.01) and CD4+ T cells (64.53% vs 79.53%, p<0.01); CD8+ T cell reductions were 75.59% (probiotic) vs 62.36% (placebo) (p<0.01). Probiotic also modulated gut microbiota toward normal, increasing Firmicutes and decreasing Bacteroidetes/Actinobacteria. In rats, probiotic cocktail reduced mucosal damage, lowered inflammatory markers, downregulated TLR4/NF-κB signaling, reduced apoptosis, and restored tight junction proteins. Conclusion: The probiotic cocktail could be a feasible preventive strategy to reduce OM during CCRT by boosting immunity and modulating gut microbiota; rat data support mechanism.

Small, single-center trial; limited sample size; some dropouts; need for larger, diverse populations; fecal microbiota transplantation suggested to confirm microbiota involvement.