化疗仍然是恶性肿瘤的主要治疗方法，但由于细胞毒性药物的副作用，特别是在老年人群中，标准剂量强度化疗的应用受到限制。细胞毒性的潜在机制以及提高化疗安全性和耐受性的策略仍有待探索。使用基础化疗药物5-氟尿嘧啶（5-FU），我们证明5-FU化疗后随意（AL）喂养的小鼠死亡的主要原因是肠道机会性病原体易位引起的感染。我们发现这些机会性病原体在化疗后肠道内大量增加，这与肠道溶菌酶的损失密切相关。值得注意的是，化疗前两周的饮食限制（DR）显着保护了溶菌酶的损失并增加了有益乳杆菌属的含量，从而显着抑制了肠道机会性病原体及其易位。 DR的救援效果可以通过溶菌酶或乳酸菌灌胃来模拟。我们的研究提供了第一个证据，表明DR实现了对肠道物理、生物和化学屏障的全面保护，从而显着提高了5-FU治疗小鼠的总体生存率。重要的是，上述发现在老年小鼠中更为突出。此外，我们发现 65 岁以上的患者肠道微生物群中机会致病菌丰富，尤其是在基于 5-FU 的化疗后。我们的研究揭示了老年人群化疗耐受性差的重要机制，短期 DR 可以显着改善这种耐受性。这项研究通过提高恶性肿瘤患者的化疗耐受性和安全性，为改善化疗预后的方法提供了新的见解。

Chemotherapy remains a major treatment for malignant tumors, yet the application of standard dose intensity chemotherapy is limited due to the side effects of cytotoxic drugs, especially in old populations. The underlying mechanisms of cytotoxicity and strategies to increase the safety and tolerance of chemotherapy remain to be explored. Using 5-fluorouracil (5-FU), a cornerstone chemotherapeutic drug, we demonstrate that the main cause of death in ad libitum (AL) fed mice after 5-FU chemotherapy was infection caused by translocation of intestinal opportunistic pathogens. We show that these opportunistic pathogens greatly increase in the intestine after chemotherapy, which was closely related to loss of intestinal lysozyme. Of note, two weeks of dietary restriction (DR) prior to chemotherapy significantly protected the loss of lysozyme and increased the content of the beneficial Lactobacillus genera, resulting in a substantial inhibition of intestinal opportunistic pathogens and their translocation. The rescue effect of DR could be mimicked by Lysozyme or Lactobacillus gavage. Our study provides the first evidence that DR achieved a comprehensive protection of the intestinal physical, biological and chemical barriers, which significantly improved the overall survival of 5-FU-treated mice. Importantly, the above findings were more prominent in old mice. Furthermore, we show that patients over 65 years old have enriched opportunistic pathogens in their gut microbiota, especially after 5-FU based chemotherapy. Our study reveals important mechanisms for the poor chemotherapy tolerance of the elderly population, which can be significantly improved by short-term DR. This study generates new insights into methods for improving the chemotherapeutic prognosis by increasing the chemotherapy tolerance and safety of patients with malignant tumors.