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Radiation Oncology Journal Jun 2023Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and...
Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. Given the role of the microbiome in radiation enteritis, we suggest that the gut microbiota may be a potential biomarker for the disease. Treatment methods such as probiotics, antibiotics, and fecal microbiota transplantation are ways to correct the microbiota and may be an effective way to prevent and treat radiation enteritis. Based on a review of the relevant literature, this paper reviews the mechanism and treatment of intestinal microbes in radiation enteritis.
PubMed: 37403348
DOI: 10.3857/roj.2023.00346 -
Microbiome May 2020We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely...
BACKGROUND
We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.
RESULTS
FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo.
CONCLUSIONS
These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.
Topics: Animals; Cell Line; Diazepam Binding Inhibitor; Fecal Microbiota Transplantation; Feces; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Hematopoiesis; Indoles; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Pregnane X Receptor; RNA, Ribosomal, 16S; Radiation Injuries; Signal Transduction
PubMed: 32434586
DOI: 10.1186/s40168-020-00845-6 -
Frontiers in Pharmacology 2023Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause... (Review)
Review
Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause radiation enteritis complications. Gastrointestinal tract contains numerous microbes, most of which are mutualistic relationship with the host. Abdominal radiation results in gut microbiota dysbiosis. Microbial therapy can directly target gut microbiota to reverse microbiota dysbiosis, hence relieving intestinal inflammation. In this review, we mainly summarized pathogenesis and novel therapy of the radiation-induced intestinal injury with gut microbiota dysbiosis and envision the opportunities and challenges of radiation enteritis therapy.
PubMed: 37063268
DOI: 10.3389/fphar.2023.1116558 -
Proceedings of the National Academy of... Oct 2022DNA-damaging treatments such as radiotherapy (RT) have become promising to improve the efficacy of immune checkpoint inhibitors by enhancing tumor immunogenicity....
DNA-damaging treatments such as radiotherapy (RT) have become promising to improve the efficacy of immune checkpoint inhibitors by enhancing tumor immunogenicity. However, accompanying treatment-related detrimental events in normal tissues have posed a major obstacle to radioimmunotherapy and present new challenges to the dose delivery mode of clinical RT. In the present study, ultrahigh dose rate FLASH X-ray irradiation was applied to counteract the intestinal toxicity in the radioimmunotherapy. In the context of programmed cell death ligand-1 (PD-L1) blockade, FLASH X-ray minimized mouse enteritis by alleviating CD8 T cell-mediated deleterious immune response compared with conventional dose rate (CONV) irradiation. Mechanistically, FLASH irradiation was less efficient than CONV X-ray in eliciting cytoplasmic double-stranded DNA (dsDNA) and in activating cyclic GMP-AMP synthase (cGAS) in the intestinal crypts, resulting in the suppression of the cascade feedback consisting of CD8 T cell chemotaxis and gasdermin E-mediated intestinal pyroptosis in the case of PD-L1 blocking. Meanwhile, FLASH X-ray was as competent as CONV RT in boosting the antitumor immune response initiated by cGAS activation and achieved equal tumor control in metastasis burdens when combined with anti-PD-L1 administration. Together, the present study revealed an encouraging protective effect of FLASH X-ray upon the normal tissue without compromising the systemic antitumor response when combined with immunological checkpoint inhibitors, providing the rationale for testing this combination as a clinical application in radioimmunotherapy.
Topics: Mice; Animals; Radioimmunotherapy; X-Rays; Pyroptosis; Immune Checkpoint Inhibitors; Ligands; Nucleotidyltransferases; Neoplasms
PubMed: 36256824
DOI: 10.1073/pnas.2208506119 -
Frontiers in Pediatrics 2021Since its clearance for use throughout the world, capsule endoscopy (CE) has become an important diagnostic tool, helping us to understand and document both normal and... (Review)
Review
Since its clearance for use throughout the world, capsule endoscopy (CE) has become an important diagnostic tool, helping us to understand and document both normal and abnormal findings in the small intestine, especially in children, since CE usually can be employed without sedation or radiation. The indications in children and adults are similar, though their relative frequencies are different, with evaluation of potential and known inflammatory bowel disease the most common in the pediatric population, with CE also yielding increased diagnostic certainty compared to radiographic studies and surrogate biomarkers. Newer capsules now create opportunities to expand that understanding and our practices so that we can learn when and how to employ CE and pan-enteric CE to better monitor and guide therapy. It will take further studies to determine the best uses for CE and how to select the appropriate candidates, especially with ongoing concern about capsule ingestion vs. placement, the potential for capsule retention (particularly in known Crohn's disease), still elusive optimal methods for bowel cleansing, and the most meaningful scoring for research and clinical use.
PubMed: 34485187
DOI: 10.3389/fped.2021.664722 -
Resveratrol attenuates radiation enteritis through the SIRT1/FOXO3a and PI3K/AKT signaling pathways.Biochemical and Biophysical Research... May 2021Radiation enteritis (RE) is the most common radiotherapy complication, and effective RE treatments are lacking. Resveratrol exerts beneficial effects on radiation...
Radiation enteritis (RE) is the most common radiotherapy complication, and effective RE treatments are lacking. Resveratrol exerts beneficial effects on radiation injury. However, the effect of resveratrol in radiation-induced intestinal injury and the underlying mechanism remain unclear. Here, a C57BL/6 mouse model of RE was established and an intestinal epithelial cell line was used to evaluate the protective effects of resveratrol against radiation-induced intestinal injury and the underlying mechanisms. Resveratrol improved radiation-induced oxidative stress and cell apoptosis via upregulating antioxidant enzymes and downregulating p53 acetylation. In vivo, resveratrol-treated mice exhibited longer survival; longer villi; more intestinal crypt cells; upregulated expression of Ki67, catalase, and superoxide dismutase 2; and fewer inflammatory proteins and apoptotic cells. These protective effects were suppressed by inhibition of SIRT1. These results demonstrate that resveratrol can reduce radiation-induced intestinal injury by inhibiting oxidative stress and apoptosis via the SIRT1/FOXO3a and PI3K/AKT pathways.
Topics: Animals; Antioxidants; Apoptosis; Cell Line; Disease Models, Animal; Enteritis; Forkhead Box Protein O3; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Radiation Injuries, Experimental; Radiation, Ionizing; Rats; Resveratrol; Signal Transduction; Sirtuin 1
PubMed: 33812084
DOI: 10.1016/j.bbrc.2021.03.122 -
Frontiers in Oncology 2022Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. The efficacy of cancer treatment by radiation is often... (Review)
Review
Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. The efficacy of cancer treatment by radiation is often limited by the side effects of Re. Re can be acute or chronic. Treatment of acute Re is essentially symptomatic. However, chronic Re usually requires surgical procedures. The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities.
PubMed: 36132154
DOI: 10.3389/fonc.2022.888962