Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 35, Issue 10, Pages -Publisher
WILEY
DOI: 10.1111/nmo.14629
Keywords
enteric nervous system; gut microbiota; intestinal motility; microbial metabolites; tryptophan synthase
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This study discovered a method to promote intestinal motility by using bacteria that produce tryptophan, possibly through increased 5-HT signaling and/or actions of tryptophan metabolites, and involvement of the 5-HT4 receptor.
BackgroundAn emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate a novel approach to promote intestinal motility by exploiting the biochemical capability of specific bacteria to produce the serotonin (5-HT) precursor, tryptophan (Trp). MethodsMice were treated daily for 1 week by oral gavage of Bacillus (B.) subtilis (R0179), heat-inactivated R0179, or a tryptophan synthase-null strain of B. subtilis (1A2). Tissue levels of Trp, 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were measured and changes in motility were evaluated. Key resultsMice treated with B. subtilis R0179 exhibited greater colonic tissue levels of Trp and the 5-HT breakdown product, 5-HIAA, compared to vehicle-treated mice. Furthermore, B. subtilis treatment accelerated colonic motility in both healthy mice as well as in a mouse model of constipation. These effects were not observed with heat-inactivated R0179 or the live 1A2 strain that does not express tryptophan synthase. Lastly, we found that the prokinetic effects of B. subtilis R0179 were blocked by coadministration of a 5-HT4 receptor (5-HT4R) antagonist and were absent in 5-HT4R knockout mice. Conclusions and inferencesTaken together, these data demonstrate that intestinal motility can be augmented by treatment with bacteria that synthesize Trp, possibly through increased 5-HT signaling and/or actions of Trp metabolites, and involvement of the 5-HT4R. Our findings provide mechanistic insight into a transient and predictable bacterial strategy to promote GI motility.
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