EA 3826 Thérapeutiques Cliniques et Expérimentales des Infections, Faculté de Médecine, Université de Nantes, Nantes, France.
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.
Aliment Pharmacol Ther. 2015 Sep;42(5):515-28. doi: 10.1111/apt.13302. Epub 2015 Jul 6.
Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome.
To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy.
We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics.
We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P = 0.0002) and Actinobacteria (P = 0.002) and significant increases in abundances of Proteobacteria (P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P = 0.0001), energy metabolism (P = 0.001), metabolism of cofactors and vitamins (P = 0.006), and increased capacity for glycan metabolism (P = 0.0002), signal transduction (P = 0.0002) and xenobiotics biodegradation (P = 0.002).
Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients.
化疗常用于作为骨髓清除性预处理，以准备患者接受造血干细胞移植（HSCT）。化疗会导致多种副作用，其中胃肠道（GI）黏膜炎是最常见的一种。目前的 GI 黏膜炎病理生理学模型普遍忽略了肠道微生物组的作用。
为了确定肠道微生物组在 GI 黏膜炎病理生理学中可能发挥关键作用的功能机制，我们应用高通量 DNA 测序分析来鉴定在化疗后发生变化的微生物和微生物功能。
我们对 28 例非霍奇金淋巴瘤患者在接受相同的骨髓清除性预处理方案且未接受其他伴随治疗（如抗生素）前后的粪便样本进行 16S rRNA 基因扩增和测序。
我们发现，与化疗前的样本相比，化疗后收集的粪便样本中厚壁菌门（Firmicutes）（P = 0.0002）和放线菌门（Actinobacteria）（P = 0.002）的丰度显著降低，变形菌门（Proteobacteria）（P = 0.0002）的丰度显著增加。化疗后，患者的核苷酸代谢（P = 0.0001）、能量代谢（P = 0.001）、辅因子和维生素代谢（P = 0.006）能力降低，聚糖代谢（P = 0.0002）、信号转导（P = 0.0002）和外源性化合物生物降解（P = 0.002）能力增加。
本研究鉴定了与化疗诱导的 GI 黏膜炎相关的肠道微生物群落的严重组成和功能失衡。我们分析中涉及的功能途径表明，针对癌症患者的肠道微生物组靶向干预具有潜在的发展方向。
