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Engineered calprotectin-sensing probiotics for IBD surveillance in humans

Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through...

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Autores principales: Xia, Jonathan Y., Hepler, Chelsea, Tran, Peter, Waldeck, Nathan J., Bass, Joseph, Prindle, Arthur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410751/
https://www.ncbi.nlm.nih.gov/pubmed/37523538
http://dx.doi.org/10.1073/pnas.2221121120
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author Xia, Jonathan Y.
Hepler, Chelsea
Tran, Peter
Waldeck, Nathan J.
Bass, Joseph
Prindle, Arthur
author_facet Xia, Jonathan Y.
Hepler, Chelsea
Tran, Peter
Waldeck, Nathan J.
Bass, Joseph
Prindle, Arthur
author_sort Xia, Jonathan Y.
collection PubMed
description Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice. Here, we introduce an engineered probiotic capable of detecting the clinical gold standard IBD biomarker, calprotectin, with sensitivity and specificity in IBD patients. Specifically, we identified a bacterial promoter in the probiotic strain Escherichia coli Nissle 1917 (EcN) which exhibits a specific expression increase in the presence of calprotectin. Using murine models of colitis, we show that the reporter signal is activated in vivo during transit of the GI tract following oral delivery. Furthermore, our engineered probiotic can successfully discriminate human patients with active IBD from those in remission and without IBD using patient stool samples, where the intensity of reporter signal quantitatively tracks with clinical laboratory–measured levels of calprotectin. Our pilot study sets the stage for probiotics that can be engineered to detect fecal calprotectin for precise noninvasive disease activity monitoring in IBD patients.
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spelling pubmed-104107512023-08-10 Engineered calprotectin-sensing probiotics for IBD surveillance in humans Xia, Jonathan Y. Hepler, Chelsea Tran, Peter Waldeck, Nathan J. Bass, Joseph Prindle, Arthur Proc Natl Acad Sci U S A Physical Sciences Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice. Here, we introduce an engineered probiotic capable of detecting the clinical gold standard IBD biomarker, calprotectin, with sensitivity and specificity in IBD patients. Specifically, we identified a bacterial promoter in the probiotic strain Escherichia coli Nissle 1917 (EcN) which exhibits a specific expression increase in the presence of calprotectin. Using murine models of colitis, we show that the reporter signal is activated in vivo during transit of the GI tract following oral delivery. Furthermore, our engineered probiotic can successfully discriminate human patients with active IBD from those in remission and without IBD using patient stool samples, where the intensity of reporter signal quantitatively tracks with clinical laboratory–measured levels of calprotectin. Our pilot study sets the stage for probiotics that can be engineered to detect fecal calprotectin for precise noninvasive disease activity monitoring in IBD patients. National Academy of Sciences 2023-07-31 2023-08-08 /pmc/articles/PMC10410751/ /pubmed/37523538 http://dx.doi.org/10.1073/pnas.2221121120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Physical Sciences
Xia, Jonathan Y.
Hepler, Chelsea
Tran, Peter
Waldeck, Nathan J.
Bass, Joseph
Prindle, Arthur
Engineered calprotectin-sensing probiotics for IBD surveillance in humans
title Engineered calprotectin-sensing probiotics for IBD surveillance in humans
title_full Engineered calprotectin-sensing probiotics for IBD surveillance in humans
title_fullStr Engineered calprotectin-sensing probiotics for IBD surveillance in humans
title_full_unstemmed Engineered calprotectin-sensing probiotics for IBD surveillance in humans
title_short Engineered calprotectin-sensing probiotics for IBD surveillance in humans
title_sort engineered calprotectin-sensing probiotics for ibd surveillance in humans
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410751/
https://www.ncbi.nlm.nih.gov/pubmed/37523538
http://dx.doi.org/10.1073/pnas.2221121120
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