肠道菌的色氨酸代谢与急性放射性肠损伤诊治的研究进展

肠道菌群不仅影响肠道细胞中色氨酸代谢限速酶的活性,而且协同产生多种催化酶直接影响肠道色氨酸代谢物的种类和数量。研究发现,在2~10.4 Gy范围内,多种肠道菌群来源的色氨酸代谢产物在全身照射后的小鼠外周血中明显减少,并与照射剂量负相关,可能是肠道急性辐射损伤相关的生物标志物。在肠道急性辐射损伤的动物模型中,肠道菌群来源的色氨酸代谢物吲哚丙酸、犬尿喹啉酸、吲哚‐3‐甲醛,肠道芳香烃受体激动剂、肠道色氨酸代谢限速酶吲哚胺2,3‐双加氧酶1抑制剂,均具有辐射防护作用。进一步研究肠道菌群参与的色氨酸代谢在急性放射性肠损伤发生发展中的变化特征和作用,筛选对肠道急性辐射损伤具有防护作用的色氨酸代谢物,可能有益于研发有效的诊治手段。

Research progress on tryptophan metabolism involved by gut microbiota in the diagnosis and treatment of acute radiation‐induced intestinal injury

Gut microbiota not only affects the activity of tryptophan metabolism rate limiting enzymes in intestinal cells, but also cooperatively produces a variety of catalytic enzymes, which directly affects the type and quantity of tryptophan metabolites in the intestine. Multiple tryptophan‐associated indole compounds originating from the gut microbiome are significantly decreased in the peripheral blood of mice, and negatively correlated with radiation dose ranging from 2 to 10.4 Gy, which might be biomarkers for acute radiation‐induced intestinal injury. Recent studies have reported that indole 3‐propionic acid (IPA), indole‐3‐carboxaldehyde (I3A) and kynurenic acid (KYNA), which are tryptophan catabolites derived from gut microbiota, aryl hydrocarbon receptor, which is one of the receptors for tryptophan catabolites, and inhibition of indoleamine 2,3 dioxygenase‐1, which is a main rate‐limiting enzyme in intestinal tryptophan catabolism, can protect against radiation‐induced intestinal toxicity. A more comprehensive understanding of the dynamics of tryptophan catabolites and their roles in acute radiation‐induced intestinal injury is needed to deepen the understanding of the pathogenesis in radiation‐induced intestinal injury and exploration of effective diagnostic and therapeutic approaches.