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Title: Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients

Abstract

Acute Coronary Syndrome (ACS) is a prime cause of morbidity and mortality. Perturbed gutmicrobiota (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. Methods: 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 using 16S 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). Interestingly, there was no differencemore » in the mean serum LPS or TMAO levels. Yet, 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.« less

Authors:
 [1]; ORCiD logo [2]; ORCiD logo [2];  [3];  [4];  [5];  [4]; ORCiD logo [2];  [2]; ORCiD logo [2];  [6]; ORCiD logo [2];  [4];  [3]
  1. Univ. of New Mexico, Albuquerque, NM (United States); Univ. of Toledo, OH (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Univ. of New Mexico, Albuquerque, NM (United States); Penn State College of Medicine, Hershey, PA (United States)
  4. Univ. of New Mexico, Albuquerque, NM (United States)
  5. Univ. of California, Irvine, CA (United States)
  6. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Viome. Inc., Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); Clinical and Translational Science Center (CTSC)
OSTI Identifier:
1545182
Alternate Identifier(s):
OSTI ID: 1558047
Report Number(s):
LA-UR-18-26913
Journal ID: ISSN 2452-2317
Grant/Contract Number:  
89233218CNA000001; 20160340ER; 20170671PRD2
Resource Type:
Published Article
Journal Name:
Human Microbiome Journal
Additional Journal Information:
Journal Volume: 13; Journal Issue: C; Journal ID: ISSN 2452-2317
Country of Publication:
United States
Language:
English
Subject:
Acute Coronary Syndrome; leaky gut; Trimethylamine-N-Oxide (TMAO), dysbiosis; gut microbiome

Citation Formats

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, Momchiloo, Chain, Patrick Sam Guy, Mishra, Shiraz, and Ma, Thomas. Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients. United States: N. p., 2019. Web. doi:10.1016/j.humic.2019.100059.
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, Momchiloo, Chain, Patrick Sam Guy, Mishra, Shiraz, & Ma, Thomas. Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients. United States. doi:10.1016/j.humic.2019.100059.
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, Momchiloo, Chain, Patrick Sam Guy, Mishra, Shiraz, and Ma, Thomas. Fri . "Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients". United States. doi:10.1016/j.humic.2019.100059.
@article{osti_1545182,
title = {Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients},
author = {Alhmoud, Tarik and Kumar, Anand and Lo, Chien-Chi and Al-Sadi, Rana and Clegg, Stacey and Alomari, Ihab and Zmeili, Tarek and Gleasne, Cheryl Diane and Mcmurry, Kim and Dichosa, Armand Earl Ko and Vuyisich, Momchiloo and Chain, Patrick Sam Guy and Mishra, Shiraz and Ma, Thomas},
abstractNote = {Acute Coronary Syndrome (ACS) is a prime cause of morbidity and mortality. Perturbed gutmicrobiota (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. Methods: 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 using 16S 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). Interestingly, there was no difference in the mean serum LPS or TMAO levels. Yet, 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.},
doi = {10.1016/j.humic.2019.100059},
journal = {Human Microbiome Journal},
number = C,
volume = 13,
place = {United States},
year = {2019},
month = {7}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.humic.2019.100059

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