Modification of the intestinal microbiota with Enterobacteriaceae-specific oligonucleotide antimicrobials as a novel approach to improve metabolic health

Wong, N., Divekar, D., D. Calvo, T., Watson, A., Mayer, M. J., McArthur, Michael and Narbad, Arjan (2024) Modification of the intestinal microbiota with Enterobacteriaceae-specific oligonucleotide antimicrobials as a novel approach to improve metabolic health. Diabetes & Obesity International Journal, 9 (2). ISSN 2574-7770

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Abstract

Imbalances in the microbiota due to overgrowth of Enterobacteriaceae is associated with numerous metabolic conditions- most notably obesity. We describe an oligonucleotide antimicrobial, Transcription Factor Decoys (TFDs) that competitively inhibit the Crp-FNR transcription factor highly conserved amongst Enterobacteriaceae and is critical for the regulation of stress response and survival under anaerobic conditions. A nanoparticulate formulation delivers the TFDs to the cytoplasm of E. coli, as visualised by confocal microscopy, rapidly reduced viable bacteria under anaerobic conditions. In vitro data showed FNR TFD decreased up to log10 6 CFU/ml of coliforms within the Enterobacteriaceae family while other families remained relatively undisturbed; similarly when delivered orally to wild-type mice in vivo, Enterobacteriaceae were significantly reduced while other key bacterial populations were unaffected. This demonstrates that TFDs can be used to make precise changes to the microbiota and has utility in testing associations between dysbiosis and disease potentially leading to the development of microbiota targeted therapeutics to tackle obesity.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	https://medwinpublishers.com/article-des...
Depositing User:	LivePure Connector
Date Deposited:	31 Jan 2025 16:30
Last Modified:	18 Feb 2025 01:21
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98340
DOI:	10.23880/doij-16000291

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