Gao Yuzheng, Liu Lidan, Cui Yuning, Zhang Jiaxin, Wu Xiuying
Department of Anesthesia, ShengJing Hospital of China Medical University, Shenyang, Liaoning, China.
Front Immunol. 2024 Apr 18;15:1266579. doi: 10.3389/fimmu.2024.1266579. eCollection 2024.
Several observational studies have proposed a potential link between gut microbiota and the onset and progression of sepsis. Nevertheless, the causality of gut microbiota and sepsis remains debatable and warrants more comprehensive exploration.
We conducted a two-sample Mendelian randomization (MR) analysis to test the causality between gut microbiota and the onset and progression of sepsis. The genome-wide association study (GWAS) summary statistics for 196 bacterial traits were extracted from the MiBioGen consortium, whereas the GWAS summary statistics for sepsis and sepsis-related outcomes came from the UK Biobank. The inverse-variance weighted (IVW) approach was the primary method used to examine the causal association. To complement the IVW method, we utilized four additional MR methods. We performed a series of sensitivity analyses to examine the robustness of the causal estimates.
We assessed the causality of 196 bacterial traits on sepsis and sepsis-related outcomes. Genus [odds ratio (OR) 0.81, 95% confidence interval (CI) (0.69-0.94), = 0.007] and genus (OR 0.85, 95% CI 0.74-0.97, = 0.016) had a protective effect on sepsis, whereas genus (OR 1.10, 95% CI 1.01-1.20, = 0.024) increased the risk of sepsis. When it came to sepsis requiring critical care, genus (OR 0.49, 95% CI 0.31-0.76, = 0.002), genus (OR 0.65, 95% CI 0.43-1.00, = 0.049), and genus (OR 0.51, 95% CI 0.34-0.77, = 0.001) emerged as protective factors. Concerning 28-day mortality of sepsis, genus (OR 0.67, 95% CI 0.48-0.94, = 0.020), genus (OR 0.48, 95% CI 0.27-0.86, = 0.013), genus (OR 0.70, 95% CI 0.52-0.95, = 0.023), and genus (OR 0.82, 95% CI 0.68-0.99, = 0.042) presented a protective effect, whereas genus (OR 1.53, 95% CI 1.00-2.35, = 0.049), genus (OR 1.25, 95% CI 1.04-1.50, = 0.019), and genus (OR 1.43, 95% CI 1.02-2.02, = 0.040) presented a harmful effect. Furthermore, genus (OR 0.42, 95% CI 0.19-0.92, = 0.031), genus (OR 0.34, 95% CI 0.14-0.83, = 0.018), and genus (OR 0.43, 95% CI 0.22-0.83, = 0.012) were associated with a lower 28-day mortality of sepsis requiring critical care.
This MR analysis unveiled a causality between the 21 bacterial traits and sepsis and sepsis-related outcomes. Our findings may help the development of novel microbiota-based therapeutics to decrease the morbidity and mortality of sepsis.
多项观察性研究提出肠道微生物群与脓毒症的发生和发展之间可能存在联系。然而，肠道微生物群与脓毒症之间的因果关系仍存在争议，值得进行更全面的探索。
我们进行了一项两样本孟德尔随机化（MR）分析，以检验肠道微生物群与脓毒症的发生和发展之间的因果关系。从MiBioGen联盟提取了196个细菌性状的全基因组关联研究（GWAS）汇总统计数据，而脓毒症和脓毒症相关结局的GWAS汇总统计数据来自英国生物银行。逆方差加权（IVW）方法是用于检验因果关联的主要方法。为补充IVW方法，我们还使用了另外四种MR方法。我们进行了一系列敏感性分析，以检验因果估计的稳健性。
我们评估了196个细菌性状对脓毒症和脓毒症相关结局的因果关系。属 [比值比（OR）0.81，95%置信区间（CI）（0.69 - 0.94）， = 0.007] 和属 （OR 0.85，95% CI 0.74 - 0.97， = 0.016）对脓毒症有保护作用，而属 （OR 1.10，95% CI 1.01 - 1.20， = 0.024）增加了脓毒症的风险。对于需要重症监护的脓毒症，属 （OR 0.49，95% CI 0.31 - 0.76， = 0.002）、属 （OR 0.65，95% CI 0.43 - 1.00， = 0.049）和属 （OR 0.51，95% CI 0.34 - 0.77， = 0.001）是保护因素。关于脓毒症的28天死亡率，属 （OR 0.67，95% CI 0.48 - 0.94， = 0.020）、属 （OR 0.48，95% CI 0.27 - 0.86， = 0.013）、属 （OR 0.70，95% CI 0.52 - 0.95， = 0.023）和属 （OR 0.82，95% CI 0.68 - 0.99， = 0.042）具有保护作用，而属 （OR 1.53，95% CI 1.00 - 2.35， = 0.049）、属 （OR 1.25，95% CI 1.04 - 1.50， = 0.019）和属 （OR 1.43，95% CI 1.02 - 2.02， = 0.040）具有有害作用。此外，属 （OR 0.42，95% CI 0.19 - 0.92， = 0.031）、属 （OR 0.34，95% CI 0.14 - 0.83， = 0.018）和属 （OR 0.43，95% CI 0.22 - 0.83， = 0.012）与需要重症监护的脓毒症较低的28天死亡率相关。
这项MR分析揭示了21个细菌性状与脓毒症及脓毒症相关结局之间的因果关系。我们的研究结果可能有助于开发基于微生物群的新型疗法，以降低脓毒症的发病率和死亡率。
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