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Article

Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite

1
Laboratory of the Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, 02–097 Warsaw, Poland
2
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02–106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6161; https://doi.org/10.3390/ijms21176161
Received: 20 July 2020 / Revised: 7 August 2020 / Accepted: 24 August 2020 / Published: 26 August 2020
Trimethylamine (TMA) is a gut bacteria product oxidized by the liver to trimethylamine-N-oxide (TMAO). Clinical evidence suggests that cardiovascular disease is associated with increased plasma TMAO. However, little headway has been made in understanding this relationship on a mechanistic and molecular level. We investigated the mechanisms affecting plasma levels of TMAO in Spontaneously Hypertensive Heart Failure (SHHF) rats. Healthy Wistar Kyoto (WKY) and SHHF rats underwent metabolic, hemodynamic, histopathological and biochemical measurements, including tight junction proteins analysis. Stool, plasma and urine samples were evaluated for TMA and TMAO using ultra performance liquid chromatography-mass spectrometry. SHHF presented disturbances of the gut–blood barrier including reduced intestinal blood flow, decreased thickness of the colonic mucosa and alterations in tight junctions, such as claudin 1 and 3, and zonula occludens-1. This was associated with significantly higher plasma levels of TMA and TMAO and increased gut-to-blood penetration of TMA in SHHF compared to WKY. There was no difference in kidney function or liver oxidation of TMA to TMAO between WKY and SHHF. In conclusion, increased plasma TMAO in heart failure rats results from a perturbed gut–blood barrier and increased gut-to-blood passage of TMAO precursor, i.e., TMA. Increased gut-to-blood penetration of bacterial metabolites may be a marker and a mediator of cardiovascular pathology. View Full-Text
Keywords: bacterial metabolites; tight junctions; TMAO; intestinal barrier; leaky gut; cardiovascular disease bacterial metabolites; tight junctions; TMAO; intestinal barrier; leaky gut; cardiovascular disease
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MDPI and ACS Style

Drapala, A.; Szudzik, M.; Chabowski, D.; Mogilnicka, I.; Jaworska, K.; Kraszewska, K.; Samborowska, E.; Ufnal, M. Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite. Int. J. Mol. Sci. 2020, 21, 6161. https://doi.org/10.3390/ijms21176161

AMA Style

Drapala A, Szudzik M, Chabowski D, Mogilnicka I, Jaworska K, Kraszewska K, Samborowska E, Ufnal M. Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite. International Journal of Molecular Sciences. 2020; 21(17):6161. https://doi.org/10.3390/ijms21176161

Chicago/Turabian Style

Drapala, Adrian, Mateusz Szudzik, Dawid Chabowski, Izabella Mogilnicka, Kinga Jaworska, Katarzyna Kraszewska, Emilia Samborowska, and Marcin Ufnal. 2020. "Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite" International Journal of Molecular Sciences 21, no. 17: 6161. https://doi.org/10.3390/ijms21176161

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