CS@LGG as a therapeutic biomaterial for acute radiation-induced bowel injury alleviation

Abstract

Acute radiation-induced bowel injury is a serious and inevitable adverse effect of pelvic radiotherapy, with few standardized therapies available in clinical practice. Interestingly, fecal microbiota transplantation (FMT) has been shown to be an effective therapeutic method. Among the probiotics, Lactobacillus rhamnosus GG (LGG) has the most prominent effect. However, due to its poor tolerance and viability in vitro and its potential to cause bacteremia in vivo, this study chose a natural and biosafe polymer called chitosan (CS) to act as a carrier, avoiding the aforementioned limitations of FMT. In this study, we successfully synthesized a curative probiotic biomaterial, named CS@LGG, to protect the intestinal epithelium from radiation-induced damage. It repaired the intestinal barrier with increased expression of occludin, claudin-3, and Ki-67, while decreasing γH2A.X. In addition, it enabled clearance of local and systemic pro-inflammatory factors, such as interleukin (IL)-6, IL1-β, and tumor necrosis factor alpha. Surprisingly, this biomaterial demonstrated good biosafety in vitro and in vivo, with a certain extent of tumor suppression. Furthermore, this study shed light on the possible mechanism underlying its therapeutic effect. RNA sequencing analysis indicated that overproduction of immunoglobulin A on local mucosa might be the core factor of damaged intestinal microenvironment leading to acute radiation-induced bowel injury. In conclusion, CS@LGG created in this work is a biosafe and effective new probiotic biomaterial that holds promise in the treatment and relief of acute radiation-induced bowel injury.

Keywords

Biomaterial / Probiotics / Acute radiation-induced bowel injury / Fecal microbiota transplantation / Radiation damage protection

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