Genotypic adaptations associated with prolonged persistence of Lactobacillus plantarum in the murine digestive tract

Authors

  • Hermien van Bokhorst-van de Veen,

    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. NIZO Food Research, Ede, The Netherlands
    3. Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, The Netherlands
    4. Food & Biobased Research, Wageningen University and Research Centre, Wageningen, The Netherlands
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  • Maaike J. Smelt,

    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. Pathology and Medical Biology, Section Immunoendocrinology, University Medical Centre Groningen, Groningen, The Netherlands
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  • Michiel Wels,

    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. NIZO Food Research, Ede, The Netherlands
    3. Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Nijmegen, The Netherlands
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  • Sacha A. F. T. van Hijum,

    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. NIZO Food Research, Ede, The Netherlands
    3. Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Nijmegen, The Netherlands
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  • Paul de Vos,

    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. Pathology and Medical Biology, Section Immunoendocrinology, University Medical Centre Groningen, Groningen, The Netherlands
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  • Prof. Michiel Kleerebezem,

    Corresponding author
    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. NIZO Food Research, Ede, The Netherlands
    3. Host-Microbe Interactomics, Wageningen University and Research Centre, Wageningen, The Netherlands
    • Host-Microbe Interactomics, Wageningen University and Research Centre, P.O. Box 338, 6700 AH Wageningen, The Netherlands
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  • Peter A. Bron

    1. TI Food & Nutrition, Wageningen, The Netherlands
    2. NIZO Food Research, Ede, The Netherlands
    3. Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands
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Abstract

Probiotic bacteria harbor effector molecules that confer health benefits, but also adaptation factors that enable them to persist in the gastrointestinal tract of the consumer. To study these adaptation factors, an antibiotic-resistant derivative of the probiotic model organism Lactobacillus plantarum WCFS1 was repeatedly exposed to the mouse digestive tract by three consecutive rounds of (re)feeding of the longest persisting colonies. This exposure to the murine intestine allowed the isolation of intestine-adapted derivatives of the original strain that displayed prolonged digestive tract residence time. Re-sequencing of the genomes of these adapted derivatives revealed single nucleotide polymorphisms as well as a single nucleotide insertion in comparison with the genome of the original WCFS1 strain. Detailed in silico analysis of the identified genomic modifications pinpointed that alterations in the coding regions of genes encoding cell envelope associated functions and energy metabolism appeared to be beneficial for the gastrointestinal tract survival of L. plantarum WCFS1. This work demonstrates the feasibility of experimental evolution for the enhancement of the gastrointestinal residence time of probiotic strains, while full-genome re-sequencing of the adapted isolates provided clues towards the bacterial functions involved. Enhanced gastrointestinal residence is industrially relevant because it enhances the efficacy of the delivery of viable probiotics in situ.

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