Volpe Robert P, Hwang Hye Jin, Cox Rachel T
Department of Biochemistry and Molecular Biology, Uniformed Services University, Bethesda, MD, 20814.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817.
bioRxiv. 2025 Jul 11:2025.07.10.664168. doi: 10.1101/2025.07.10.664168.
Diverse fungi have been historically vital reservoirs of drug discovery, providing life-saving pharmaceuticals. Many species of fungi, yeasts in particular, are highly resistant to radiation, with their cellular contents potentially conferring dietary radioresistance. We developed a model to test whether feeding two highly radioresistant fungi, and , could improve fly lifespan and gut morphology after acute irradiation. We constructed a dosimetry curve for the lifespan response of males and females to irradiation and found dose-dependent and sex-specific effects on lifespan. We also determined that the sex-specific response to irradiation correlated with nuclear morphology defects in the gut, with the more radiosensitive males displaying increased midgut cellular holes and aberrant nuclear morphology. To determine if feeding and before irradiation could improve survival and gut morphology, we first exclusively fed males and females each fungus and observed that they tolerated the diet well. Using these methods, we found that only two days of prefeeding increased male lifespan, but not female, after irradiation, and improved nuclear morphology in the gut. However, dietary was not protective. Overall, this study identified a highly radioresistant dietary fungus, , as effective for extending male lifespan and improving gut morphology following irradiation. Since the gut is particularly sensitive to the effects of irradiation, this fungus indicates a potential therapeutic for patients undergoing radiotherapy. Furthermore, this method could identify additional radioresistant fungi that protect the gut from radiation injury.
从历史上看，多种真菌一直是药物发现的重要来源，提供了挽救生命的药物。许多真菌物种，尤其是酵母，对辐射具有高度抗性，其细胞成分可能赋予饮食抗辐射能力。我们开发了一个模型，以测试喂食两种高度抗辐射的真菌，即[真菌名称1]和[真菌名称2]，是否能在急性辐射后延长果蝇寿命并改善肠道形态。我们构建了雄性和雌性果蝇对辐射寿命反应的剂量测定曲线，发现对寿命存在剂量依赖性和性别特异性影响。我们还确定，对辐射的性别特异性反应与肠道中的核形态缺陷相关，辐射敏感性更高的雄性果蝇中肠细胞孔洞增加且核形态异常。为了确定在辐射前喂食[真菌名称1]和[真菌名称2]是否能提高存活率和改善肠道形态，我们首先分别给雄性和雌性果蝇喂食每种真菌，观察到它们对这种饮食耐受性良好。使用这些方法，我们发现辐射后仅提前两天喂食[真菌名称1]可延长雄性果蝇寿命，但对雌性无效，且改善了肠道中的核形态。然而，喂食[真菌名称2]没有保护作用。总体而言，本研究确定了一种高度抗辐射的饮食真菌，即[真菌名称1]，对延长雄性果蝇寿命和改善辐射后的肠道形态有效。由于肠道对辐射影响特别敏感，这种真菌表明对接受放疗的患者具有潜在治疗作用。此外，这种方法可以识别出其他能保护肠道免受辐射损伤的抗辐射真菌。
