Relationship Between Radiation Enteritis And Gut Microbiota In Patients With Uterine Malignant Tumor:A Pilot Study

Objectives:The purpose of this study is to explore the relationship between radiation enteritis and gut microbiota in patients with uterine malignant tumor,so as to provide some inspiration for microbial therapy and prevention of radiation enteritis in patients with uterine malignant tumor.Methods:Acute radiation enteritis group,Feces samples were collected from 37 cervical and endometrial cancer patients receiving radiotherapy that included radical radiotherapy(RR)and postoperative radiotherapy(PR).Fecal samples were collected before radiotherapy and 3 weeks after radiotherapy.Symptoms were recorded according to the grade of diarrhea and proctitis in CTCAE5.0.Any symptom grade 2 or above were considered high symptom grade(HG),and the others were low symptom grade(LG).Chronic radiation enteritis group,Fecal samples were collected from 34 patients with cervical cancer who had received radiotherapy for at least 6 months but less than 2 years.Patients were divided into M(mild)group with no symptoms or mild symptoms and S(severe)group with severe symptoms by clinical diagnosis of radiation enteritis,modified inflammatory bowel disease questionnaire(IBDQ)and Vaizey questionnaire.DNA extracted from fecal samples was sequenced and analyzed by 16S rRNA sequencing method.Analysis indexes included α-diversity,β-diversity,taxonomic composition analysis,taxonomic hierarchy tree,linear discriminant analysis effect size(LEfSe)and MetagenomeSeq analysis.Results:(1)Acute radiation enteritis group,The a diversity of gut microbiota was significantly higher in LG patients than that in HG patients before radiotherapy(p<0.05).And there were also differences in β diversity between the two groups.Ruminococcus-gnavus was significantly higher in HG than LG before radiotherapy(p=0.0023),it may be a biomarker for predicting the severity of radiation enteritis before radiotherapy.After 3 weeks of radiotherapy,the gut microbiota in LG and HG showed different changes.F aecalibacterium-prausnitzii(p=0.0225),Gemmiger-formicilis(p=0.0011)and unclassified-Ruminococcaceae(p=0.0019)in LG group were significantly up-regulated before radiotherapy compared with after radiotherapy.Faecalibacterium-prausnitzii(p=0.0000)in HG group were significantly up-regulated before radiotherapy compared with after radiotherapy.In addition,RR patients had higher gut microbiota diversity and less severe of radiation enteritis than PR patients.Faecalibacterium-prausnitzii was significantly higher in RR than PR before radiotherapy(p=0.0047),and it may be negatively correlated with radiation toxicity.(2)Chronic radiation enteritis group.From the perspective of species diversity,most indices of a diversity in group M were higher than those in group S.Although there was no significant difference,it also indicated a correlation between low species diversity and severity of intestinal symptoms to some extent.There were also significant differences inβ-diversity between the two groups.From the perspective of species composition,the M group had higher Firmicutes(M66.5%/S56.0%)and lower Proteobacteria(M4.1%/S13.9%)than the S group at the level of phyla.At the level of genus,there were also significant differences between the two groups:Shigella(M2.7%/S8.5%),Faecalibacterium(M7.0%/S2.7%),Lachnospiraceae-clostridium(M1.3%/S4.7%).LEfSe also found some species with significant differences between the two groups.The abundance of Peptoniphilus,Azospirillum and Actinomyces in group M was significantly higher,while the abundance of Veillonellaceae,Rhodobacteraceae,Rhodobacterales in group S was significantly higher.Finally,the taxonomic hierarchy tree also shows the difference in species composition between the two groups at each taxonomic level.Conclusion:(1)Acute and chronic radiation enteritis in patients with uterine malignant tumor is closely related to the composition and characteristics of gut microbiota.(2)Patients with lower intestinal microbial diversity are more likely to have more severe acute and chronic radiation enteritis.(3)The rich aggregation of Ruminococcus-gnavus aggravates acute radiation enteritis in patients with uterine malignant tumor.The enrichment of Faecalibacterium was negatively correlated with the severity of acute and chronic radiation enteritis in patients with uterine malignant tumor.The results provide experimental basis for microbiological therapy to prevent and treat acute and chronic radiation enteritis in patients with uterine malignant tumor.