Abstract
Pelvic radiotherapy is known to evoke intestinal mucositis and dysbiosis. Currently, there are no effective therapies available to mitigate these injuries, which is partly due to a lack of insight into the events causing mucositis and dysbiosis. Here, the complex interplay between the murine host and its microbiome following pelvic irradiation was mapped by characterizing intestinal mucositis along with extensive 16S microbial profiling. We demonstrated important morphological and inflammatory implications within one day after exposure, thereby impairing intestinal functionality and inducing translocation of intraluminal bacteria into mesenteric lymph nodes as innovatively quantified by flow cytometry. Concurrent 16S microbial profiling revealed a delayed impact of pelvic irradiation on beta diversity. Analysis of composition of microbiomes identified biomarkers for pelvic irradiation. Among them, members of the families Ruminococcaceae, Lachnospiraceae and Porphyromonadaceae were differentially affected. Altogether, our unprecedented findings showed how pelvic irradiation evoked structural and functional changes in the intestine, which secondarily resulted in a microbiome shift. Therefore, the presented in vivo irradiation-gut-microbiome platform allows further research into the pathobiology of pelvic irradiation-induced intestinal mucositis and resultant dysbiosis, as well as the exploration of mitigating treatments including drugs and food supplements.
Highlights
Gut dysbiosis is generally defined as the qualitatively and quantitatively altered composition of intestinal microbiota, which offers an advantage for emergence and outbreak of pathogens and has a cascading impact on the immune system.[1]
The major limitation in the search for new food supplements is the lack of mechanistic understanding of the events underlying irradiation-induced intestinal mucositis and dysbiosis, as well as the lack of an appropriate research model system
Cellculture set-ups based on intestinal epithelial cells are largely incomplete to capture the complexity of the intestinal tissue, the gut microbiome and the underlying pathobiology of irradiationinduced enteropathy.[7,8,9,10]
Summary
Gut dysbiosis is generally defined as the qualitatively and quantitatively altered composition of intestinal microbiota, which offers an advantage for emergence and outbreak of pathogens and has a cascading impact on the immune system.[1]. There are no effective therapies available to mitigate irradiation-induced intestinal mucositis in human patients Given their safe character, food supplements including probiotics, prebiotics, and vitamins are being investigated for their potential to provide radioprotection and re-establish an orthobiotic (i.e., balanced composition providing beneficial effects to the host) gut microbiome.[5] For example, the probiotic preparation VSL#3 reduced the severity and incidence of irradiation-induced diarrhea in a Phase II clinical trial.[6] The major limitation in the search for new food supplements is the lack of mechanistic understanding of the events underlying irradiation-induced intestinal mucositis and dysbiosis, as well as the lack of an appropriate research model system. Our research presents an in vivo irradiation-gut-microbiome test platform to study the pathobiology and new potential treatments for pelvic irradiation-induced intestinal mucositis and secondary gut microbial dysbiosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
