Gut Microbiota Dysbiosis Mediates 125I-Induced Radiation Colitis via Host Transcriptional Regulation.

BACKGROUND

Iodine-125 (125I) seed therapy is recognized for treating abdominal solid tumors with minimal adjacent tissue damage but may induce radiation colitis when its implantation near colonic tissues, leading to a poor prognosis. Nevertheless, the underlying pathogenesis is not well understood.

OBJECTIVE

This research aims to investigate the role of gut microbiota and host immune-transcriptional responses in the pathogenesis of 125I-induced radiation colitis.

METHODS

We implanted 125I seeds intraperitoneally in mice and assessed colonic damage via histology, TUNEL staining, cytokine assays, and tight‑junction protein measurements. Fecal microbiota were profiled by 16S rRNA sequencing, and colonic transcriptomes by RNA‑seq. Multi‑omics integration (Spearman correlation, KEGG, RDA, Procrustes) was used to link microbial taxa, differentially expressed genes, and pathological features.

RESULTS

125I exposure caused mucosal necrosis, lowered ZO-1 and occludin levels, and raised IL-1α, IL-1β, IL-6, and TNF-α. 16S rRNA sequencing revealed altered microbial β-diversity and dysbiosis, characterized by reduced Lachnospiraceae, Mucispirillum, and Desulfovibrio, and increased Clostridium methylpentosum and Bifidobacterium. RNA-seq analysis revealed differentially expressed genes such as Angptl7, Apoh, C7, and Ccl7. Integrated analyses, including Spearman correlation, KEGG enrichment, redundancy analysis, and Procrustes analysis, confirmed strong associations between certain microbes, host gene expression, and pathological phenotypes.

CONCLUSION

Our findings indicate that 125I irradiation is associated with gut dysbiosis and concurrent host immune‑transcriptional reprogramming, which may jointly contribute to radiation colitis. Although these results lay a foundation for microbiota‑targeted interventions, the causative role of microbial changes remains to be confirmed by functional experiments.