Introduction: Gut microbiota plays a major role in the development and modulation of immune and inflammatory responses. Recently, it has been found that gut microbiota is involved in the pathogenesis of chemotherapy and immunotherapy-induced gastrointestinal mucositis through inflammatory responses modulation.
Aim: This study aimed to determine whether gut microbiota has an impact on the development and severity of radiation-induced oral mucositis (OM) in a rat model.
Methods: 24 male Sprague Dawley rats were divided into two groups; antibiotic treatment/radiation group (ABxRx, n=12) and radiation only (Rx, n=12). To deplete gut microbiota, ABxRx rats were provided with an antibiotic cocktail for three weeks in drinking water. All rats were exposed to single-dose radiation of 20 Gy x-ray to the snout. Rats were culled at two time points, day 9 and day 15 post-radiation with tongue collected for the analysis of OM severity.
Results: OM developed from day 5 and peaked on day 9. OM severity score was similar in both groups (3.8 ± 0.3 ABxRx group vs 4.5 ± 0.3 Rx group, p=ns). However, there was a significant difference in the duration of severe OM (grade 4-5) between groups (ABxRx 2 ± 0.3 vs Rx 3.5 ± 0.5 days, p= 0.0408). Moreover, the area of ulcered mucosa was smaller in ABxRx (18.9%) compared to Rx (33.3%) (p=0.02). In addition, there was a reduction in body weight in both groups between day 8 and day 11, however, ABxRx recovered faster and gained more weight after day 11 (ABxRx 7% vs Rx 2% weight gain, p=ns).
Conclusion: Antibiotic-depletion of gut microbiota significantly reduced severe OM duration and ulcer-like area in the tongue. Future analysis will determine if gut microbiota eradication also reduces oral histopathological injury and inflammatory markers, which would provide evidence for gut microbiota targeting to reduce OM in clinical settings.