Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT

Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT
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DOI:
10.1182/blood-2018-01-828996
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发表时间:
2018-06-28
期刊:
影响因子:
20.3
通讯作者:
Taur, Ying
Taur, Ying
中科院分区:
医学1区
文献类型:
--
作者:
Haak, Bastiaan W.;Littmann, Eric R.;Taur, Ying

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呼吸道病毒感染在接受异基因造血干细胞移植(allo-HCT)的患者中很常见,并可能进展为下呼吸道感染(LRTI)。肠道微生物群有助于抵抗肺部的病毒和细菌病原体。然而,在allo-HCT的情况下,肠道微生物群组成和微生物衍生代谢物的相关变化是否有助于上呼吸道病毒感染后LRTI的风险仍然未被探索。在干细胞植入时收集来自360名allo-HCT患者的粪便样本,并进行深度16 S核糖体RNA基因测序以确定微生物群组成,并在粪便样本的巢式子集中确定短链脂肪酸水平。在allo-HCT后180天确定呼吸道病毒感染和LRTI的发展。随后使用生存分析评估LRTI的临床和微生物群风险因素。149例(41.4%)患者发生呼吸道病毒感染。其中,47例(31.5%)发生LRTI。丁酸盐产生菌丰度较高的患者发生病毒性下呼吸道感染的可能性降低5倍,与其他因素无关(校正后的风险比为0.22,95%置信区间为0.04-0.69)。粪便微生物群中丁酸盐产生菌的较高代表性与allo-HCT患者对LRTI呼吸道病毒感染的抵抗力增加相关。
Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio 5 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.