Fatigue and
diarrhea are the most frequent adverse effects of pelvic
radiotherapy, while their etiologies are largely unknown. The aim of this study is to investigate the correlations between
fatigue,
diarrhea, and alterations in gut microbiota induced by pelvic
radiotherapy. During the 5-week treatment of pelvic
radiotherapy in 11
cancer patients, the general
fatigue score significantly increased and was more prominent in the patients with
diarrhea. The
fatigue score was closely correlated with the decrease of serum
citrulline (an
indicator of the functional enterocyte mass) and the increases of systemic inflammatory
proteins, including
haptoglobin, orosomuoid, α1-antitrypsin and TNF-α. Serum level of
lipopolysaccharide (LPS) was also elevated, especially in the patients with
diarrhea indicating epithelial barrier breach and
endotoxemia. Pyrosequencing analysis of
16S rRNA gene revealed that microbial diversity, richness, and the Firmicutes/Bacteroidetes ratio were significantly altered prior to
radiotherapy in patients who later developed
diarrhea. Pelvic
radiotherapy induced further changes in fecal microbial ecology, some of which were specific to the patients with or without
diarrhea. Our results indicate that gut microbial
dysbiosis prior to
radiation therapy may be exploited to predict development of
diarrhea and to guide preventive treatment options. Radiation-induced
dysbiosis may contribute to pelvic radiation disease, including
mucositis,
diarrhea, systemic inflammatory response, and pelvic
radiotherapy-associated
fatigue in
cancer patients.