Alhmoud Tarik, Kumar Anand, Lo Chien-Chi, Al-Sadi Rana, Clegg Stacey, Alomari Ihab, Zmeili Tarek, Gleasne Cheryl Diane, Mcmurry Kim, Dichosa Armand Earl Ko, Vuyisich Momchilo, Chain Patrick Sam Guy, Mishra Shiraz, Ma Thomas
University of New Mexico Health Science Center, 2400 Tucker Ave NE, Albuquerque, NM 87131, USA.
Biosecurity and Public Health Group, Bioscience Division, Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, NM 87545, USA.
Hum Microb J. 2019 Aug;13. doi: 10.1016/j.humic.2019.100059. Epub 2019 Jul 19.
Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Perturbed gut- microbiota (dysbiosis) and increased intestinal permeability (leaky-gut) with translocation of bacterial antigens, play critical role in obesity and metabolic syndrome, which are also major ACS risk factors. Additionally, Trimethylamine-N-Oxide (TMAO), a metabolite produced by phylum Proteobacteria in gut is implicated in developing ACS. As Proteobacteria is a major source of translocated antigen lipopolysaccharides (LPS), we hypothesized that ACS patients have leaky-gut condition characterized by dysbiosis with increased Proteobacteria, leading to elevated blood levels of TMAO and LPS.
In a pilot case-control study, we enrolled 19 ACS patients (within 72-h of cardiac events) and 19 healthy-controls. Gut barrier function was determined using lactulose-to-mannitol urinary excretion ratio (L/M ratio). Stool microbiome composition was examined using16S sequencing and predictive functional analysis for LPS biosynthesis pathway by PICRUSt tool. Serum TMAO and LPS levels were measured.
ACS patients had increased Gammaproteobacteria compared to controls:1.8 ±3.0 vs. 0.2 ±0.4% (P =0.04). Though Proteobacteria level was increased but not statistically significant: 4.1 ±3.8 vs. 2.1 ±1.7% (P =0.056). L/M-ratio was three times higher in ACS patients; 0.06 ±0.07 vs 0.023 ±0.02, (P =0.014). Surprisingly, there was no difference in the mean serum LPS or TMAO levels. However, PICRUSt analysis indicated increased Proteobacteria population increasingly contributed to LPS biosynthesis in ACS patients only.
ACS patients likely to have leaky-gut and perturbed gut microbiota. Further studies are required to precisely define the role of dysbiosis in ACS.
急性冠状动脉综合征（ACS）是发病和死亡的主要原因。肠道微生物群紊乱（生态失调）以及肠道通透性增加（肠漏）和细菌抗原易位，在肥胖和代谢综合征中起关键作用，而肥胖和代谢综合征也是主要的ACS危险因素。此外，肠道中变形菌门产生的代谢产物氧化三甲胺（TMAO）与ACS的发生有关。由于变形菌是易位抗原脂多糖（LPS）的主要来源，我们推测ACS患者存在肠漏情况，其特征是生态失调，变形菌增加，导致血液中TMAO和LPS水平升高。
在一项初步病例对照研究中，我们招募了19名ACS患者（心脏事件发生后72小时内）和19名健康对照者。使用乳果糖与甘露醇尿排泄率（L/M比）来确定肠道屏障功能。通过16S测序检查粪便微生物群组成，并使用PICRUSt工具对LPS生物合成途径进行预测功能分析。测量血清TMAO和LPS水平。
与对照组相比，ACS患者的γ-变形菌增加：1.8±3.0%对0.2±0.4%（P = 0.04）。虽然变形菌水平有所增加，但无统计学意义：4.1±3.8%对2.1±1.7%（P = 0.056）。ACS患者的L/M比高出三倍；0.06±0.07对0.023±0.02，（P = 0.014）。令人惊讶的是，血清LPS或TMAO平均水平没有差异。然而，PICRUSt分析表明，仅ACS患者中增加的变形菌群体对LPS生物合成的贡献越来越大。
ACS患者可能存在肠漏和肠道微生物群紊乱。需要进一步研究以准确界定生态失调在ACS中的作用。
