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
N1 - Funding Information:
This project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant UL1TR001449, the University of New Mexico Clinical and Translational Science Center. This project was also partially supported by a Los Alamos National Laboratory (LANL) internal Grants, the Laboratory Directed Research and Development Grant 20160340ER and the LANL Director's Postdoctoral Fellowship, Grant 20170671PRD2. Jessica Hancock: clinical coordinator who recruited patients, collected and processed human samples. Clinical and Translational Science Center (CTSC) at the University of New Mexico for providing funding for the study and providing clinic space, laboratory work including DNA extraction, sample storage and shipment, and recruitment of healthy controls.
Funding Information:
This project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant UL1TR001449 , the University of New Mexico Clinical and Translational Science Center . This project was also partially supported by a Los Alamos National Laboratory (LANL) internal Grants, the Laboratory Directed Research and Development Grant 20160340ER and the LANL Director’s Postdoctoral Fellowship , Grant 20170671PRD2 .
Publisher Copyright:
© 2019 Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PY - 2019/8
Y1 - 2019/8
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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U2 - 10.1016/j.humic.2019.100059
DO - 10.1016/j.humic.2019.100059
M3 - Article
AN - SCOPUS:85069639515
SN - 2452-2317
VL - 13
JO - Human Microbiome Journal
JF - Human Microbiome Journal
M1 - 100059
ER -