Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing

Abstract

Although pelvic irradiation is effective for the treatment of various cancer types, many patients who receive radiotherapy experience serious complications. Gut microbial dysbiosis was hypothesized to be related to the occurrence of radiation-induced complications in cancer patients. Given the lack of clinical or experimental data on the impact of radiation on gut microbiota, a prospective observational study of gut microbiota was performed in gynecological cancer patients receiving pelvic radiotherapy. In the current study, the overall composition and alteration of gut microbiota in cancer patients receiving radiation were investigated by 454 pyrosequencing. Gut microbial composition showed significant differences (P < 0.001) between cancer patients and healthy individuals. The numbers of species-level taxa were severely reduced after radiotherapy (P < 0.045), and the abundance of each community largely changed. In particular, the phyla Firmicutes and Fusobacterium were significantly decreased by 10% and increased by 3% after radiation therapy, respectively. In addition, overall gut microbial composition was gradually remolded after the full treatment course of pelvic radiotherapy. In this set of cancer patients, dysbiosis of the gut microbiota was linked to health status, and the gut microbiota was influenced by pelvic radiotherapy. Although further studies are needed to elucidate the relationship between dysbiosis and complications induced by pelvic radiotherapy, the current study may offer insights into the treatment of cancer patients suffering from complications after radiation therapy.

Figure 1. Comparison of bacterial communities between healthy individuals and patients.

Relative abundances of six phylum-level taxa are compared (A). Each bar represents the mean value of abundance (± SEM). P-values showing the significance of differences between cancer patient and healthy individual groups are shown at the upper part of each graph. Overall species-level bacterial communities were compared and clustered by the UPGMA algorithm (B) and visualized by PCoA plots (C) with the Jaccard coefficient; RI, RK, RL, RM, RN, and RO represent healthy individuals, and AT0 to IT0 represents gynecological cancer patients before radiotherapy.

Figure 2. Impact of radiation therapy on the gut microbial community.

Unique sequences, observed OTUs, estimated OTUs, and diversity indices (H) according to radiation therapy were analyzed (A). The mean number (± SEM) of each parameter is shown. P-values between T0 and T3 are marked. Changes of six major phylum-level taxa during radiation therapy are represented (B). The mean abundance (± SEM) is shown. P-values representing significant differences are only shown for each taxonomic group. T0 = before radiation therapy, T1 = after first radiation therapy, T2 = after fifth radiation therapy, and T3 = follow-up samples.

Figure 3. Changes of gut bacterial family level taxa in gynecological cancer patients through the radiotherapy.

Each column in the heatmap represents a sample from nine cancer patients. Three or four samples from the same individuals were grouped together in parallel. Each row represents a family level taxon. The color intensity of the panel is proportional to the abundance of certain taxon (max 5%). The family level taxon name is represented on the right side of heatmap.

Figure 4. PCoA comparison of gut microbiota during radiation therapy.

Distances between all communities were clustered with the Jaccard (A) and thetayc coefficient (B) and visualized with PCoA plots. All plots in a stage (T0, T1, T2, and T3) are separately marked in the different graphs to represent the change of similarity between communities in a stage. Average distances (± SD) between all plots are represented at the lower part of each graph.