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      Gut microbiota derived trimethylamine N-oxide (TMAO) detection through molecularly imprinted polymer based sensor

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          Abstract

          Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite has been implicated in human health and disease. Its early detection in body fluids has been presumed to be significant in understanding the pathogenesis and treatment of many diseases. Hence, the development of reliable and rapid technologies for TMAO detection may augment our understanding of pathogenesis and diagnosis of diseases that TMAO has implicated. The present work is the first report on the development of a molecularly imprinted polymer (MIP) based electrochemical sensor for sensitive and selective detection of TMAO in body fluids. The MIP developed was based on the polypyrrole (PPy), which was synthesized via chemical oxidation polymerization method, with and without the presence of TMAO. The MIP, NIP and the non-sonicated polymer (PPy-TMAO) were separately deposited electrophoretically onto the hydrolyzed indium tin oxide (ITO) coated glasses. The chemical, morphological, and electrochemical behavior of MIP, non-imprinted polymer (NIP), and PPy-TMAO were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and electrochemical techniques. The detection response was recorded using differential pulse voltammetry (DPV), which revealed a decrease in the peak current with the increase in concentration of TMAO. The MIP sensor showed a dynamic detection range of 1–15 ppm with a sensitivity of 2.47 µA mL ppm −1 cm −2. The developed sensor is easy to construct and operate and is also highly selective to detect TMAO in body fluids such as urine. The present research provides a basis for innovative strategies to develop sensors based on MIP to detect other metabolites derived from gut microbiota that are implicated in human health and diseases.

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          Most cited references59

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          Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

          Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.
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            Recent advances in molecular imprinting technology: current status, challenges and highlighted applications.

            Molecular imprinting technology (MIT) concerns formation of selective sites in a polymer matrix with the memory of a template. Recently, molecularly imprinted polymers (MIPs) have aroused extensive attention and been widely applied in many fields, such as solid-phase extraction, chemical sensors and artificial antibodies owing to their desired selectivity, physical robustness, thermal stability, as well as low cost and easy preparation. With the rapid development of MIT as a research hotspot, it faces a number of challenges, involving biological macromolecule imprinting, heterogeneous binding sites, template leakage, incompatibility with aqueous media, low binding capacity and slow mass transfer, which restricts its applications in various aspects. This critical review briefly reviews the current status of MIT, particular emphasis on significant progresses of novel imprinting methods, some challenges and effective strategies for MIT, and highlighted applications of MIPs. Finally, some significant attempts in further developing MIT are also proposed (236 references).
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              Molecularly imprinted polymers and their use in biomimetic sensors.

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                Author and article information

                Contributors
                anilk@nii.ac.in
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 January 2021
                14 January 2021
                2021
                : 11
                : 1338
                Affiliations
                [1 ]GRID grid.10706.30, ISNI 0000 0004 0498 924X, Special Center for Nanoscience, , Jawaharlal Nehru University, ; New Delhi, India
                [2 ]GRID grid.444644.2, ISNI 0000 0004 1805 0217, Amity Institute of Applied Sciences, Amity University, Uttar Pradesh, ; Noida, India
                [3 ]GRID grid.411524.7, ISNI 0000 0004 1790 2262, Department of Zoology, , Maharshi Dayanand University, ; Rohtak, 124001 India
                [4 ]GRID grid.19100.39, ISNI 0000 0001 2176 7428, National Institute of Immunology, ; New Delhi, India
                Article
                80122
                10.1038/s41598-020-80122-6
                7809026
                33446682
                60cf88c2-b602-443c-8cb7-34860e7dfa4a
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 June 2020
                : 15 December 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001407, Department of Biotechnology, Ministry of Science and Technology, India;
                Funded by: ICMR
                Award ID: Pratima R. Solanki
                Award ID: Pratima R. Solanki
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001409, Department of Science and Technology, Ministry of Science and Technology, India;
                Award ID: PURSE
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100011753, National Institute of Immunology;
                Funded by: FundRef http://dx.doi.org/10.13039/501100001843, Science and Engineering Research Board;
                Categories
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                © The Author(s) 2021

                Uncategorized
                biotechnology,cancer,biomarkers,diseases,health occupations,medical research,engineering,materials science,nanoscience and technology

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