Tryptophan-synthesizing bacteria enhance colonic motility

Area of Science:

• Microbiology and Gut Physiology
• Gastrointestinal Motility Research
• Microbiome-Host Interactions

Background:

• Gastrointestinal (GI) dysmotility is increasingly treated with isolated bacteria.
• Mechanisms underlying bacterial treatment for GI dysmotility are not well understood.
• This study explores bacterial production of tryptophan (Trp) to enhance intestinal motility.

Purpose of the Study:

• To investigate the role of bacterial tryptophan synthesis in promoting intestinal motility.
• To elucidate the mechanism by which bacteria influence gut motility via tryptophan and serotonin pathways.
• To evaluate the involvement of the serotonin 5-HT4 receptor in bacterial-mediated prokinetic effects.

Main Methods:

• Oral gavage administration of Bacillus subtilis strains (R0179, tryptophan synthase-null 1A2) or heat-inactivated bacteria in mice.
• Measurement of tissue levels of tryptophan (Trp), serotonin (5-HT), and 5-HIAA.
• Assessment of colonic motility in healthy and constipated mouse models, with and without 5-HT4 receptor antagonists or in knockout mice.

Main Results:

• Bacillus subtilis R0179 treatment increased colonic Trp and 5-HIAA levels.
• B. subtilis R0179 accelerated colonic motility in healthy and constipated mice.
• Prokinetic effects were dependent on live bacteria expressing tryptophan synthase and involved the 5-HT4 receptor.

Conclusions:

• Bacteria synthesizing Trp can augment intestinal motility, potentially via enhanced serotonin signaling.
• The findings highlight a novel mechanism involving tryptophan metabolism and the 5-HT4 receptor in bacterial-mediated gut motility.
• This provides mechanistic insight into using specific bacteria to promote GI motility.