A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers

There is a need for large-scale, longitudinal studies to determine the mechanisms by which the gut microbiome and its interactions with the host affect human health and disease. Current methods for profiling the microbiome typically utilize next-generation sequencing applications that are expensive,...

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Main Authors: Donghia, Nina, Ananthakrishnan, Ashwin, Takahashi, Melissa Kimie, Tan, Xiao, Dy, Aaron James, Braff, Dana, Akana, Reid T., Furuta, Yoshikazu, Collins, James J.
Other Authors: Institute for Medical Engineering and Science
Format: Article
Published: Nature Publishing Group 2018
Online Access:http://hdl.handle.net/1721.1/117563
https://orcid.org/0000-0002-3198-5944
https://orcid.org/0000-0003-0319-5416
https://orcid.org/0000-0003-4710-1389
https://orcid.org/0000-0002-5560-8246
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author Donghia, Nina
Ananthakrishnan, Ashwin
Takahashi, Melissa Kimie
Tan, Xiao
Dy, Aaron James
Braff, Dana
Akana, Reid T.
Furuta, Yoshikazu
Collins, James J.
author2 Institute for Medical Engineering and Science
author_facet Institute for Medical Engineering and Science
Donghia, Nina
Ananthakrishnan, Ashwin
Takahashi, Melissa Kimie
Tan, Xiao
Dy, Aaron James
Braff, Dana
Akana, Reid T.
Furuta, Yoshikazu
Collins, James J.
author_sort Donghia, Nina
collection MIT
description There is a need for large-scale, longitudinal studies to determine the mechanisms by which the gut microbiome and its interactions with the host affect human health and disease. Current methods for profiling the microbiome typically utilize next-generation sequencing applications that are expensive, slow, and complex. Here, we present a synthetic biology platform for affordable, on-demand, and simple analysis of microbiome samples using RNA toehold switch sensors in paper-based, cell-free reactions. We demonstrate species-specific detection of mRNAs from 10 different bacteria that affect human health and four clinically relevant host biomarkers. We develop a method to quantify mRNA using our toehold sensors and validate our platform on clinical stool samples by comparison to RT-qPCR. We further highlight the potential clinical utility of the platform by showing that it can be used to rapidly and inexpensively detect toxin mRNA in the diagnosis of Clostridium difficile infections.
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spelling mit-1721.1/1175632022-09-30T20:38:24Z A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers Donghia, Nina Ananthakrishnan, Ashwin Takahashi, Melissa Kimie Tan, Xiao Dy, Aaron James Braff, Dana Akana, Reid T. Furuta, Yoshikazu Collins, James J. Institute for Medical Engineering and Science Massachusetts Institute of Technology. Department of Biological Engineering Takahashi, Melissa Kimie Tan, Xiao Dy, Aaron James Braff, Dana Akana, Reid T. Furuta, Yoshikazu Collins, James J. There is a need for large-scale, longitudinal studies to determine the mechanisms by which the gut microbiome and its interactions with the host affect human health and disease. Current methods for profiling the microbiome typically utilize next-generation sequencing applications that are expensive, slow, and complex. Here, we present a synthetic biology platform for affordable, on-demand, and simple analysis of microbiome samples using RNA toehold switch sensors in paper-based, cell-free reactions. We demonstrate species-specific detection of mRNAs from 10 different bacteria that affect human health and four clinically relevant host biomarkers. We develop a method to quantify mRNA using our toehold sensors and validate our platform on clinical stool samples by comparison to RT-qPCR. We further highlight the potential clinical utility of the platform by showing that it can be used to rapidly and inexpensively detect toxin mRNA in the diagnosis of Clostridium difficile infections. National Institutes of Health (U.S.) (Grant T32-DK007191) 2018-08-27T19:37:05Z 2018-08-27T19:37:05Z 2018-08 2017-12 2018-08-27T17:08:44Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/117563 Takahashi, Melissa K. et al. “A Low-Cost Paper-Based Synthetic Biology Platform for Analyzing Gut Microbiota and Host Biomarkers.” Nature Communications 9, 1 (August 2018): 3347 https://orcid.org/0000-0002-3198-5944 https://orcid.org/0000-0003-0319-5416 https://orcid.org/0000-0003-4710-1389 https://orcid.org/0000-0002-5560-8246 http://dx.doi.org/10.1038/s41467-018-05864-4 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature
spellingShingle Donghia, Nina
Ananthakrishnan, Ashwin
Takahashi, Melissa Kimie
Tan, Xiao
Dy, Aaron James
Braff, Dana
Akana, Reid T.
Furuta, Yoshikazu
Collins, James J.
A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers
title A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers
title_full A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers
title_fullStr A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers
title_full_unstemmed A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers
title_short A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers
title_sort low cost paper based synthetic biology platform for analyzing gut microbiota and host biomarkers
url http://hdl.handle.net/1721.1/117563
https://orcid.org/0000-0002-3198-5944
https://orcid.org/0000-0003-0319-5416
https://orcid.org/0000-0003-4710-1389
https://orcid.org/0000-0002-5560-8246
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