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Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells

Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effe...

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Autores principales: Jalandra, Rekha, Makharia, Govind K., Sharma, Minakshi, Kumar, Anil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885123/
https://www.ncbi.nlm.nih.gov/pubmed/36726978
http://dx.doi.org/10.3389/fimmu.2022.1101429
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author Jalandra, Rekha
Makharia, Govind K.
Sharma, Minakshi
Kumar, Anil
author_facet Jalandra, Rekha
Makharia, Govind K.
Sharma, Minakshi
Kumar, Anil
author_sort Jalandra, Rekha
collection PubMed
description Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium.
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spelling pubmed-98851232023-01-31 Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells Jalandra, Rekha Makharia, Govind K. Sharma, Minakshi Kumar, Anil Front Immunol Immunology Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium. Frontiers Media S.A. 2023-01-16 /pmc/articles/PMC9885123/ /pubmed/36726978 http://dx.doi.org/10.3389/fimmu.2022.1101429 Text en Copyright © 2023 Jalandra, Makharia, Sharma and Kumar https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Jalandra, Rekha
Makharia, Govind K.
Sharma, Minakshi
Kumar, Anil
Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
title Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
title_full Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
title_fullStr Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
title_full_unstemmed Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
title_short Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
title_sort inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885123/
https://www.ncbi.nlm.nih.gov/pubmed/36726978
http://dx.doi.org/10.3389/fimmu.2022.1101429
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