Cargando…

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

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 molecu...

Descripción completa

Detalles Bibliográficos
Autores principales: Drapala, Adrian, Szudzik, Mateusz, Chabowski, Dawid, Mogilnicka, Izabella, Jaworska, Kinga, Kraszewska, Katarzyna, Samborowska, Emilia, Ufnal, Marcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504565/
https://www.ncbi.nlm.nih.gov/pubmed/32859047
http://dx.doi.org/10.3390/ijms21176161
_version_ 1783584654031323136
author Drapala, Adrian
Szudzik, Mateusz
Chabowski, Dawid
Mogilnicka, Izabella
Jaworska, Kinga
Kraszewska, Katarzyna
Samborowska, Emilia
Ufnal, Marcin
author_facet Drapala, Adrian
Szudzik, Mateusz
Chabowski, Dawid
Mogilnicka, Izabella
Jaworska, Kinga
Kraszewska, Katarzyna
Samborowska, Emilia
Ufnal, Marcin
author_sort Drapala, Adrian
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7504565
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75045652020-09-24 Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite Drapala, Adrian Szudzik, Mateusz Chabowski, Dawid Mogilnicka, Izabella Jaworska, Kinga Kraszewska, Katarzyna Samborowska, Emilia Ufnal, Marcin Int J Mol Sci Article 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. MDPI 2020-08-26 /pmc/articles/PMC7504565/ /pubmed/32859047 http://dx.doi.org/10.3390/ijms21176161 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Drapala, Adrian
Szudzik, Mateusz
Chabowski, Dawid
Mogilnicka, Izabella
Jaworska, Kinga
Kraszewska, Katarzyna
Samborowska, Emilia
Ufnal, Marcin
Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
title Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
title_full Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
title_fullStr Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
title_full_unstemmed Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
title_short Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
title_sort heart failure disturbs gut–blood barrier and increases plasma trimethylamine, a toxic bacterial metabolite
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504565/
https://www.ncbi.nlm.nih.gov/pubmed/32859047
http://dx.doi.org/10.3390/ijms21176161
work_keys_str_mv AT drapalaadrian heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT szudzikmateusz heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT chabowskidawid heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT mogilnickaizabella heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT jaworskakinga heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT kraszewskakatarzyna heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT samborowskaemilia heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite
AT ufnalmarcin heartfailuredisturbsgutbloodbarrierandincreasesplasmatrimethylamineatoxicbacterialmetabolite