Adelaide Medical School, The University of Adelaide , Adelaide, Australia.
Department of Pediatrics, University Medical Centre Groningen, The University of Groningen , Groningen, The Netherlands.
Gut Microbes. 2020 Nov 9;12(1):1-9. doi: 10.1080/19490976.2020.1809332.
Recent findings by Tang et al. (2020) show dietary restriction (30%, 2 weeks) prevents methotrexate-induced mortality by modulation of the microbiota, specifically the expansion of . While fundamentally insightful, upscaling this schedule is a major obstacle to clinical uptake. Here, we evaluate a safe and clinically achievable schedule of pre-therapy fasting for 48 h on microbiota composition, body composition and intestinal proliferation, and assess its impact on the severity of methotrexate-induced gastrointestinal mucositis using a validated preclinical rat model.
Age- and weight-matched male Wistar rats were treated with a sublethal dose of 45 mg/kg methotrexate with or without pre-therapy fasting. The impact of acute fasting on epithelial proliferation, body composition and the microbiota was assessed using plasma citrulline, Ki67 immunohistochemistry, miniSpec and 16S rRNA sequencing. The severity of gastrointestinal mucositis was evaluated using plasma citrulline and body weight.
Whilst pre-therapy fasting slowed epithelial proliferation and increased microbial diversity and richness, it also induced significant weight loss and was unable to attenuate the severity of mucositis in both age- and weight-matched groups. In contrast to Tang et al., we saw no expansion of following acute fasting.
Our findings suggest that the beneficial effects of acute fasting are masked by the detrimental effects on body weight and composition and lacking influence on . Future studies should consider alternative fasting schedules or aim to induce comparable microbial and mucosal manipulation without compromising body composition using clinically feasible methods of dietary or microbial intervention.
最近，Tang 等人的研究结果表明，饮食限制（30%，2 周）通过调节微生物群来预防甲氨蝶呤引起的死亡率，特别是 的扩张。虽然从根本上具有洞察力，但扩大这种方案是临床应用的主要障碍。在这里，我们评估了一种安全且在临床可行的 48 小时预治疗禁食方案对微生物群组成、身体成分和肠道增殖的影响，并使用经过验证的临床前大鼠模型评估其对甲氨蝶呤引起的胃肠道粘膜炎严重程度的影响。
年龄和体重匹配的雄性 Wistar 大鼠用亚致死剂量的 45mg/kg 甲氨蝶呤治疗，并用或不用预治疗禁食。使用血浆瓜氨酸、Ki67 免疫组织化学、miniSpec 和 16S rRNA 测序评估急性禁食对上皮细胞增殖、身体成分和微生物群的影响。使用血浆瓜氨酸和体重评估胃肠道粘膜炎的严重程度。
尽管预治疗禁食会减缓上皮细胞增殖并增加微生物多样性和丰富度，但它也会导致明显的体重减轻，并且无法减轻年龄和体重匹配组中粘膜炎的严重程度。与 Tang 等人不同，我们没有看到急性禁食后 的扩张。
我们的研究结果表明，急性禁食的有益效果被体重和成分的不利影响所掩盖，并且对 没有影响。未来的研究应考虑替代禁食方案，或旨在在不影响身体成分的情况下通过临床可行的饮食或微生物干预方法诱导类似的微生物和粘膜操作。
