一项关于菊粉预防脓毒症重症监护病房患者肠道病原菌定植和感染的2期随机、安慰剂对照试验。
A phase 2 randomized, placebo-controlled trial of inulin for the prevention of gut pathogen colonization and infection among patients admitted to the intensive care unit for sepsis.
作者信息
Park Heekuk, Lynch Elissa, Tillman Alice, Lewis Kristen, Jin Zhezhen, Uhlemann Anne-Catrin, Abrams Julian A, Freedberg Daniel E
机构信息
Division of Infectious Diseases & Microbiome Core Facility, Columbia University Irving Medical Center, 630 West 168th Street, PS 9-428, New York, NY, 10032, USA.
Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, 630 West 168th Street, P&S 3-401, New York, NY, 10032, USA.
出版信息
Crit Care. 2025 Jan 13;29(1):21. doi: 10.1186/s13054-024-05232-3.
BACKGROUND
Patients admitted to the intensive care unit (ICU) often have gut colonization with pathogenic bacteria and such colonization is associated with increased risk for death and infection. We conducted a trial to determine whether a prebiotic would improve the gut microbiome to decrease gut pathogen colonization and decrease downstream risk for infection among newly admitted medical ICU patients with sepsis.
METHODS
This was a randomized, double-blind, placebo-controlled trial of adults who were admitted to the medical ICU for sepsis and were receiving broad-spectrum antibiotics. Participants were randomized 1:1:1 to placebo, inulin 16 g/day, or inulin 32 g/day which were given for seven days. The trial primary outcome was a surrogate measure for gut colonization resistance, namely the within-individual change from ICU admission to Day 3 in the relative abundance of short chain fatty acid (SCFA)-producing bacteria based on rectal swabs. Additional outcomes sought to evaluate the impact of inulin on the gut microbiome and downstream clinical effects.
RESULTS
Ninety participants were analyzed including 30 in each study group. There was no difference between study groups in the within-individual change in the relative abundance of SCFA-producing bacteria from ICU admission to ICU Day 3 (placebo: 0.0% change, IQR - 8·0% to + 7·4% vs. combined inulin: 0·0% change, IQR - 10·1% to + 4·8%; p = 0·91). At end-of-treatment on ICU Day 7, inulin did not affect SCFA-producer levels, microbiome diversity, or rates of gut colonization with pathogenic bacteria. After 30 days of clinical follow-up, inulin did not affect rates of death or clinical, culture-proven infection. Patients who died or developed culture-proven infections had lower relative abundance of SCFA-producing bacteria at ICU admission compared to those who did not (p = 0·03).
CONCLUSIONS
Prebiotic fiber had minimal impact on the gut microbiome in the ICU and did not improve clinical outcomes.
TRIAL REGISTRATION
Clinicaltrials.gov: NCT03865706.
背景
入住重症监护病房（ICU）的患者肠道常被病原菌定植，这种定植与死亡和感染风险增加相关。我们开展了一项试验，以确定益生元是否会改善肠道微生物群，从而减少肠道病原菌定植，并降低新入院的脓毒症医学ICU患者的下游感染风险。
方法
这是一项针对因脓毒症入住医学ICU且正在接受广谱抗生素治疗的成年人的随机、双盲、安慰剂对照试验。参与者按1:1:1随机分为接受安慰剂、16克/天菊粉或32克/天菊粉治疗，为期7天。试验的主要结局是肠道定植抗性的替代指标，即根据直肠拭子，从ICU入院到第3天，个体体内产生短链脂肪酸（SCFA）的细菌相对丰度的变化。其他结局旨在评估菊粉对肠道微生物群和下游临床效果的影响。
结果
分析了90名参与者，每个研究组各30名。从ICU入院到ICU第3天，各研究组之间产生SCFA的细菌相对丰度的个体内变化无差异（安慰剂组：变化0.0%，四分位距-8.0%至+7.4%；联合菊粉组：变化0.0%，四分位距-10.1%至+4.8%；p = 0.91）。在ICU第7天治疗结束时，菊粉不影响产生SCFA的细菌水平、微生物群多样性或肠道病原菌定植率。经过30天的临床随访，菊粉不影响死亡率或临床确诊感染率。与未死亡或未发生临床确诊感染的患者相比，死亡或发生临床确诊感染的患者在ICU入院时产生SCFA的细菌相对丰度较低（p = 0.03）。
结论
益生元纤维对ICU患者的肠道微生物群影响极小，且未改善临床结局。
试验注册
Clinicaltrials.gov：NCT03865706。
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