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

T. Alhmoud, A. Kumar, Chien Chi Lo, Rana Al-Sadi, Stacey Clegg, Ihab Alomari, T. Zmeili, Cheryl Diane Gleasne, Kim Mcmurry, Armand Earl Ko Dichosa, Momchiloo Vuyisich, Patrick Sam Guy Chain, Shiraz Mishra, Thomas Ma

Research output: Contribution to journalArticle

Abstract

Background: 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. 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 using16S sequencing and predictive functional analysis for LPS biosynthesis pathway by PICRUSt tool. Serum TMAO and LPS levels were measured. Results: 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. Conclusions: ACS patients likely to have leaky-gut and perturbed gut microbiota. Further studies are required to precisely define the role of dysbiosis in ACS.

Original languageEnglish (US)
Article number100059
JournalHuman Microbiome Journal
Volume13
DOIs
StatePublished - Aug 1 2019

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Acute Coronary Syndrome
Permeability
Proteobacteria
Lipopolysaccharides
Dysbiosis
Gastrointestinal Microbiome
Bacterial Antigens
Gammaproteobacteria
Lactulose
Microbiota
Mannitol
Serum
Case-Control Studies
Obesity
Morbidity
Antigens
Mortality
trimethyloxamine

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Alhmoud, T. ; Kumar, A. ; Lo, Chien Chi ; Al-Sadi, Rana ; Clegg, Stacey ; Alomari, Ihab ; Zmeili, T. ; 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. In: Human Microbiome Journal. 2019 ; Vol. 13.
@article{6dd2e241fa064dd088f14de8330d0d48,
title = "Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients",
abstract = "Background: 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. 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 using16S sequencing and predictive functional analysis for LPS biosynthesis pathway by PICRUSt tool. Serum TMAO and LPS levels were measured. Results: 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. Conclusions: ACS patients likely to have leaky-gut and perturbed gut microbiota. Further studies are required to precisely define the role of dysbiosis in ACS.",
author = "T. Alhmoud and A. Kumar and Lo, {Chien Chi} and Rana Al-Sadi and Stacey Clegg and Ihab Alomari and T. Zmeili and Gleasne, {Cheryl Diane} and Kim Mcmurry and Dichosa, {Armand Earl Ko} and Momchiloo Vuyisich and Chain, {Patrick Sam Guy} and Shiraz Mishra and Thomas Ma",
year = "2019",
month = "8",
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doi = "10.1016/j.humic.2019.100059",
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Alhmoud, T, Kumar, A, Lo, CC, Al-Sadi, R, Clegg, S, Alomari, I, Zmeili, T, Gleasne, CD, Mcmurry, K, Dichosa, AEK, Vuyisich, M, Chain, PSG, Mishra, S & Ma, T 2019, 'Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients', Human Microbiome Journal, vol. 13, 100059. https://doi.org/10.1016/j.humic.2019.100059

Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients. / Alhmoud, T.; Kumar, A.; Lo, Chien Chi; Al-Sadi, Rana; Clegg, Stacey; Alomari, Ihab; Zmeili, T.; Gleasne, Cheryl Diane; Mcmurry, Kim; Dichosa, Armand Earl Ko; Vuyisich, Momchiloo; Chain, Patrick Sam Guy; Mishra, Shiraz; Ma, Thomas.

In: Human Microbiome Journal, Vol. 13, 100059, 01.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients

AU - Alhmoud, T.

AU - Kumar, A.

AU - Lo, Chien Chi

AU - Al-Sadi, Rana

AU - Clegg, Stacey

AU - Alomari, Ihab

AU - Zmeili, T.

AU - Gleasne, Cheryl Diane

AU - Mcmurry, Kim

AU - Dichosa, Armand Earl Ko

AU - Vuyisich, Momchiloo

AU - Chain, Patrick Sam Guy

AU - Mishra, Shiraz

AU - Ma, Thomas

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: 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. 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 using16S sequencing and predictive functional analysis for LPS biosynthesis pathway by PICRUSt tool. Serum TMAO and LPS levels were measured. Results: 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. Conclusions: ACS patients likely to have leaky-gut and perturbed gut microbiota. Further studies are required to precisely define the role of dysbiosis in ACS.

AB - Background: 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. 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 using16S sequencing and predictive functional analysis for LPS biosynthesis pathway by PICRUSt tool. Serum TMAO and LPS levels were measured. Results: 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. Conclusions: ACS patients likely to have leaky-gut and perturbed gut microbiota. Further studies are required to precisely define the role of dysbiosis in ACS.

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DO - 10.1016/j.humic.2019.100059

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