skip to main content
Show search Show menu
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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:
; ORCiD logo; ; ; ; ; ; ; ; ; ; ; ;
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; LA-UR-19-31930
Journal ID: ISSN 2452-2317; S2452231719300107; 100059; PII: S2452231719300107
Grant/Contract Number:  
20160340ER; 20170671PRD2; 89233218CNA000001
Resource Type:
Journal Article: Published Article
Journal Name:
Human Microbiome Journal
Additional Journal Information:
Journal Name: Human Microbiome Journal Journal Volume: 13 Journal Issue: C; Journal ID: ISSN 2452-2317
Publisher:
Elsevier
Country of Publication:
Country unknown/Code not available
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 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. Country unknown/Code not available: N. p., 2019. Web. doi:10.1016/j.humic.2019.100059.
Copy to clipboard
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. Country unknown/Code not available. https://doi.org/10.1016/j.humic.2019.100059
Copy to clipboard
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. 2019. "Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients". Country unknown/Code not available. https://doi.org/10.1016/j.humic.2019.100059.
Copy to clipboard
@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},
url = {https://www.osti.gov/biblio/1545182}, journal = {Human Microbiome Journal},
issn = {2452-2317},
number = C,
volume = 13,
place = {Country unknown/Code not available},
year = {Thu Aug 01 00:00:00 EDT 2019},
month = {Thu Aug 01 00:00:00 EDT 2019}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.1016/j.humic.2019.100059
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal

Figures / Tables:

Table 1 Table 1: Baseline characteristics of ACS patients and healthy controls.
All figures and tables (5 total)
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

The heart and the gut
journal, July 2013

Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors
journal, October 2012

Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults
journal, February 2010

The Human Intestinal Microbiome in Health and Disease
journal, December 2016

Modulating the innate immune response by combinatorial engineering of endotoxin
journal, January 2013

Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
journal, March 2014

Association of endotoxemia with carotid atherosclerosis and cardiovascular disease
journal, December 1999

Expression of the Lipopolysaccharide-Modifying Enzymes PagP and PagL Modulates the Endotoxic Activity of Bordetella pertussis
journal, October 2006

CD14 C(-260)T promoter polymorphism and prevalence of acute coronary syndromes
journal, February 2005

Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
journal, April 2013

Human oral, gut, and plaque microbiota in patients with atherosclerosis
journal, October 2010

Intra-individual variation of plasma trimethylamine-N-oxide (TMAO), betaine and choline over 1 year
journal, January 2017

The Human Microbiome Project
journal, October 2007

Automated enzymatic assays for the determination of intestinal permeability probes in urine. 1. Lactulose and lactose
journal, February 1990

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans
journal, May 2016

Toll-like Receptor 4 Polymorphisms and Atherogenesis
journal, July 2002

Leaky gut and diabetes mellitus: what is the link?: Leaky gut in diabetes
journal, March 2011

The Long-Term Stability of the Human Gut Microbiota
journal, July 2013

The Treatment-Naive Microbiome in New-Onset Crohn’s Disease
journal, March 2014

Proteobacteria: microbial signature of dysbiosis in gut microbiota
journal, September 2015

The gut microbiome in atherosclerotic cardiovascular disease
journal, October 2017

Microbial Enterotypes, Inferred by the Prevotella-to-Bacteroides Ratio, Remained Stable during a 6-Month Randomized Controlled Diet Intervention with the New Nordic Diet
journal, December 2013

Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
journal, April 2013

Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
journal, November 2012

    Sort options
    [ × clear filter / sort ]

    Figures / Tables found in this record:

    Table 1(p. 4)table
    Fig. 1(p. 5)figure
    Fig. 2(p. 6)figure
    Fig. 3.(p. 7)figure
    Fig. 4(p. 8)figure
      Sort options
      [ × clear filter / sort ]
      Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.

      Similar records in OSTI.GOV collections: