Intestinal mucositis is a common side effect of chemotherapy leading to diarrhea, abdominal pain and increased risk of infections. The intestinal microbiota has been recognized as a key regulator of mucosal immune responses. Therefore, we hypothesized that intestinal microbial changes would be associated with enterocyte loss and systemic inflammation during induction treatment for childhood acute lymphoblastic leukemia (ALL). We prospectively included 51 children newly‐diagnosed with ALL treated in Denmark in 2015–2018. Plasma C‐reactive protein (CRP), plasma citrulline (marker of functional enterocytes mass) measurements and fecal samplings were performed on treatment Days 1, 8, 15, 22 and 29. Moreover, intestinal mucositis was scored by a trained nurse/physician. Fecal samples in patients and 19 healthy siblings were analyzed by 16S rRNA gene sequencing (V3–V4 region). Bacterial alpha diversity was lower in patients compared to siblings. It decreased from Day 1 to Days 8–22 and increased on Day 29. Shannon alpha diversity index was correlated with CRP on Days 15–29 (rho = −0.33−0.49; p  < 0.05) and with citrulline on Days 15 and 29 (although with p values <0.06, rho = 0.32–0.34). The abundance of unclassified Enterococcus species (spp.) was correlated with CRP on Days 22–29 (rho = 0.42–0.49; p  < 0.009), while the abundance of unclassified Lachnospiraceae spp. was correlated with citrulline on days 8–15 (rho = 0.48–0.62, p  < 0.001). Systemic inflammation, enterocyte loss and relative abundance of unclassified Enterococcus spp. reached a peak around Day 15. In conclusion, specific changes in the microbiota were associated with the severity of enterocyte loss and systemic inflammation during chemotherapy.

中文翻译：

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儿童急性淋巴细胞白血病诱导治疗期间的胃肠道毒性：肠道菌群的影响。

肠粘膜炎是化学疗法的常见副作用，可导致腹泻，腹痛和感染风险增加。肠道菌群已被认为是黏膜免疫反应的关键调节因子。因此，我们假设在儿童急性淋巴细胞白血病（ALL）的诱导治疗过程中，肠道微生物的变化与肠细胞的丢失和全身炎症有关。我们前瞻性地纳入了2015–2018年在丹麦接受治疗的51名新诊断为ALL的儿童。在治疗的第1、8、15、22和29天进行血浆C反应蛋白（CRP），血浆瓜氨酸（功能性肠上皮细胞质量的标志）的测量和粪便采样。此外，由受过训练的护士/医师对肠粘膜炎进行评分。通过16S rRNA基因测序（V3-V4区域）分析了患者和19个健康兄弟姐妹的粪便样本。与兄弟姐妹相比，患者的细菌α多样性较低。它从第1天下降到第8-22天，并在第29天上升。香农α多样性指数在15-29天与CRP相关（rho = -0.33-0.49；p  <0.05）和在第15和29天使用瓜氨酸（尽管p值<0.06，rho = 0.32-0.34）。未分类肠球菌种类（spp。）的丰度与第22–29天的CRP相关（rho = 0.42–0.49; p  <0.009），而未分类Lachnospiraceae spp。在第8-15天与瓜氨酸相关（rho = 0.48-0.62，p  <0.001）。未分类肠球菌的系统性炎症，肠上皮细胞损失和相对丰度。在第15天左右达到高峰。总之，微生物群的特定变化与化疗期间肠细胞丢失的严重程度和全身炎症有关。