Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.
Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.
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DOI：
10.1016/j.chom.2015.09.008
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发表时间：
2015-10-14
影响因子：
30.3
通讯作者：
Bushman FD
中科院分区：
文献类型：
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作者：
Lewis JD;Chen EZ;Baldassano RN;Otley AR;Griffiths AM;Lee D;Bittinger K;Bailey A;Friedman ES;Hoffmann C;Albenberg L;Sinha R;Compher C;Gilroy E;Nessel L;Grant A;Chehoud C;Li H;Wu GD;Bushman FD
肠道细菌的异常组成-“生态失调”-是克罗恩病的特征。疾病治疗包括饮食改变和免疫抑制性抗TNF α抗体以及辅助抗生素治疗，但其对微生物群组成的影响尚未确定。使用鸟枪法宏基因组测序，我们分析了来自开始肠内营养或抗TNF α抗体治疗的儿童克罗恩病患者前瞻性队列的粪便样本，并揭示了治疗期间细菌、真菌、古菌和病毒的完整补体和动力学。细菌群落成员与肠道炎症、抗生素使用和治疗独立相关。抗生素暴露与微生态失调增加有关，而微生态失调随着肠道炎症的减少而减少。真菌比例随着疾病和抗生素的使用而增加。饮食疗法对微生物群组成具有独立和快速的影响，与其他应激源诱导的变化不同，并有效地减少炎症。这些发现揭示了生态失调是由炎症、饮食和抗生素的独立影响引起的，并为克罗恩病的治疗提供了线索。
Abnormal composition of intestinal bacteria —“dysbiosis”— is characteristic of Crohn’s disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn’s disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.