Pelvic radiotherapy induces dysbiosis of gut microbiota and enteric infection in mice

Abstract

Objective To explore the changes of gut microbiota in response to abdominal and pelvic radiotherapy and its potential relationship with intestinal infection. Methods Irradiation was delivered to the abdominal region of BALB/c mice, following the regular human pelvic-radiotherapy protocol, 2.0 Gy/d, continuous 5 d/week. Samples of ileum tissue and the intestinal content were collected at different time points of irradiation procedure, including after 3 and 5 weeks, and at 1 week after 6 weeks of irradiation. Quantitative RT-PCR was used to measure the mRNA level of antimicrobial peptides and pro-inflammtory factors. Bacterial translocation was determined by PCR. The gut microbiota was characterized by the denaturing gradient electrophoresis assay. Results The expressions of cryptdin-1 and cryptdin-4 were decreased after 3 weeks of irradiation and at 1 week after 6 weeks of irradiation(t=-7.43, -3.54, -4.72, -4.27, P<0.05), while they were significantly increased at the 5 weeks of radiation (t=6.15, 5.75, P<0.05). The diversity index and richness of gut microbiota after 3 or 5 weeks irradiation were significantly decreased (t=-3.49, -4.19, -3.44, -4.97, P<0.05). The gut microbiota dysbiosis of the irradiated mice was characterized with the decrease of probiotics of Lactobacillus and the increasing of opportunistic pathogen of Escherichia coli, Shigella flexneri, et al. Bacterial translocation episodes were more frequently in the irradiated mice than that of control animal. The mRNA levels of IL-1β、IL-6 and TNF-α were significantly increased after 3 or 5 weeks of irradiation (t=4.85, 6.16, 7.71, 4.60, 4.86, 5.97, P<0.05). Compared with the control, the expression levels of IL-1β and TNF-α at the 1 week after 6 weeks of irradiation ending was also obviously enhanced (t=3.67, 5.88, P<0.05). Conclusions Pelvic radiotherapy can induce abnormality of enteric antimicrobial peptides and may result in gut microbiota dysbiosis. The disturbed gut microbial flora may further trigger an incurrence of bacterial translocation and enteritis. Therefore, the gut microbiota may be a potential interfering target to alleviate radiotherapy adverse effect. Key words: Radiation; Microbiota dysbiosis; Intestinal inflammation; Intestinal infection; Radiotherapy adverse effect