重症监护病房微生物组计划：重症与微生物多样性丧失和细菌重要变化相关
肠道和口腔细菌菌群变化与多样性的丧失被认为与重症监护病房（ICU）患者感染并发症和死亡相关。然而，迄今为止，ICU患者的微生物生态学评价仅限于小型培养研究。随着16s rRNA微生物组技术的发展，需要对ICU微生物组进行大规模前瞻研究。
美国科罗拉多大学医学院、科罗拉多大学博尔德分校、加拿大维多利亚女王大学、美国圣迭戈加利福尼亚大学对4个重症监护病房（ICU）的149例患者进行了多中心前瞻研究，采用16s rRNA测序和宏基因组的方法，分析肠道、口咽部和皮肤的微生物组成。结果表明，与正常对照组相比，ICU患者这三个部位的微生物多样性均显著降低，并与不良临床结局（如死亡、ARDS、ICU住院时间）密切相关。这可能为今后利用微生物进行疾病的诊断和治疗提供理论基础。
JPEN J Parenter Enteral Nutr. 2016;40:123-124.
ICU Microbiome Project: Critical Illness Is Associated With Loss of Microbial Diversity and Major Alterations in Bacterial Flora.
Paul Wischmeyer; Daniel McDonald; Daren Heyland; Ludmila Khailova; Christine Baird; Rob Knight.
University of Colorado School of Medicine, Aurora, CO, USA; University of Colorado at Boulder, Boulder, CO, USA; Queens University, Kingston, Ontario, Canada; University of California-San Diego, San Diego, CA, USA.
Purpose: Alterations and loss of diversity in gut and oral bacterial flora (dysbiosis) are thought to be associated with infectious complications and mortality in ICU patients. However, to date, evaluations of microbial ecology in ICU patients have been restricted to small culture-based studies. With the evolution of 16s rRNA microbiome techniques, large-scale prospective trials of the ICU microbiome are needed. Thus, we conducted a multicenter prospective trial of the effect of critical illness on gut, oropharynx, and skin microbiome via 16s sequencing and metagenomics versus healthy controls.
Methods: Fecal, oral, and skin samples were collected in 149 mixed ICU patients in 4 centers from the United States and Canada at 2 time points: within 48 hours of ICU admission and discharge or day 10 (whichever came first). Sample collection and processing were performed in accordance with Earth Microbiome Project protocols. Results were compared with samples from self-reported healthy individuals (ie, no antibiotic use in last year; n = 1242 [American Gut Registry]). Diverse clinical outcomes were collected, including mortality, key infections, antibiotic use, and all nutrition delivery data.
Results: Regardless of time point, fecal, oral, and skin ICU samples were significantly different from American Gut healthy samples within principal coordinates space, a separation predominantly explained by a decreased ratio of firmicute abundance. Correlations were observed with changes in microbiome signatures from all sites with adverse outcomes, including mortality, ARDS, and length of stay. A significant “crash” in taxon diversity was observed in fecal/oral samples, with only a few (1 to <5 taxa) making up 95% of entire bacterial population in many ICU patients (showing rank abundance of most abundant operational taxonomic unit in ICU and healthy control patients). As an example, reduced microbiome diversity was associated with longer ICU length of stay (Mann U, P = .008). Many operational taxonomic units significantly depleted in ICU patients have been identified as “health-promoting species” in studies of other diseases states (ie, IBD), such as Faecalibacterium prausnitzii.
Conclusions: These initial data suggest that significant changes in the gut, oral, and skin microbiome occur in ICU patients, including significant loss of bacterial diversity. This loss of diversity can be extreme, with very few taxa making up a significant portion of the fecal and oral microbiome of ICU patients. This loss of diversity appears to be correlated with worsened clinical outcomes. Characterizing these changes opens the door to asking focused questions to understand why these differences arise, and it forms the basis for the development of diagnostic and therapeutic interventions, such as probiotics, prebiotics, and stool transplants utilizing microbiome signatures to guide therapy.
Financial support: National Institutes of Health (R01 GM078312).
