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Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides

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  • Seth G. Kabonick

    (Penn State College of Medicine
    Pennsylvania State University
    Pennsylvania State University)

  • Kamalesh Verma

    (Penn State College of Medicine
    Pennsylvania State University
    Pennsylvania State University)

  • Jennifer L. Modesto

    (Penn State College of Medicine
    Pennsylvania State University
    Pennsylvania State University)

  • Victoria H. Pearce

    (Penn State College of Medicine
    Pennsylvania State University
    Pennsylvania State University)

  • Kailyn M. Winokur

    (Penn State College of Medicine
    Pennsylvania State University
    Pennsylvania State University)

  • Eduardo A. Groisman

    (Yale University School of Medicine)

  • Guy E. Townsend

    (Penn State College of Medicine
    Pennsylvania State University
    Pennsylvania State University)

Abstract

Human dietary choices control the gut microbiome. Industrialized populations consume abundant amounts of glucose and fructose, resulting in microbe-dependent intestinal disorders. Simple sugars inhibit the carbohydrate utilization regulator (Cur), a transcription factor in members of the prominent gut bacterial phylum, Bacteroidetes. Cur controls products necessary for carbohydrate utilization, host immunomodulation, and intestinal colonization. Here, we demonstrate how simple sugars decrease Cur activity in the mammalian gut. Our findings in two Bacteroides species show that ATP-dependent fructose-1,6-bisphosphate (FBP) synthesis is necessary for glucose or fructose to inhibit Cur, but dispensable for growth because of an essential pyrophosphate (PPi)-dependent enzyme. Furthermore, we show that ATP-dependent FBP synthesis is required to regulate Cur in the gut but does not contribute to fitness when cur is absent, indicating PPi is sufficient to drive glycolysis in these bacteria. Our findings reveal how sugar-rich diets inhibit Cur, thereby disrupting Bacteroides fitness and diminishing products that are beneficial to the host.

Suggested Citation

  • Seth G. Kabonick & Kamalesh Verma & Jennifer L. Modesto & Victoria H. Pearce & Kailyn M. Winokur & Eduardo A. Groisman & Guy E. Townsend, 2025. "Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59704-3
    DOI: 10.1038/s41467-025-59704-3
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    References listed on IDEAS

    as
    1. Chun-Ying Wang & Martin Lempp & Niklas Farke & Stefano Donati & Timo Glatter & Hannes Link, 2021. "Metabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Morgan N. Price & Kelly M. Wetmore & R. Jordan Waters & Mark Callaghan & Jayashree Ray & Hualan Liu & Jennifer V. Kuehl & Ryan A. Melnyk & Jacob S. Lamson & Yumi Suh & Hans K. Carlson & Zuelma Esquive, 2018. "Mutant phenotypes for thousands of bacterial genes of unknown function," Nature, Nature, vol. 557(7706), pages 503-509, May.
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