The microbiota drives diurnal rhythms in tryptophan metabolism in the stressed gut

• Published in: Cell reports (Cambridge) Vol. 43; no. 4; p. 114079
• Main Authors: Gheorghe, Cassandra E., Leigh, Sarah-Jane, Tofani, Gabriel S.S., Bastiaanssen, Thomaz F.S., Lyte, Joshua M., Gardellin, Elisa, Govindan, Ashokkumar, Strain, Conall, Martinez-Herrero, Sonia, Goodson, Michael S., Kelley-Loughnane, Nancy, Cryan, John F., Clarke, Gerard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.04.2024; Elsevier
• Subjects: acute stress; Animals; Circadian Rhythm - physiology; circadian rhythms; CP: Metabolism; CP: Microbiology; Gastrointestinal Microbiome - physiology; gut barrier; gut function; gut permeability; indole metabolites; Male; Mice; Mice, Inbred C57BL; microbial metabolites; microbiota-gut-brain axis; Stress, Physiological; Tryptophan - metabolism; gut function; microbial metabolites; tryptophan metabolism; gut permeability; CP: Metabolism; acute stress; CP: Microbiology; microbiota-gut-brain axis; indole metabolites; circadian rhythms; gut barrier
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114079

Chronic stress disrupts microbiota-gut-brain axis function and is associated with altered tryptophan metabolism, impaired gut barrier function, and disrupted diurnal rhythms. However, little is known about the effects of acute stress on the gut and how it is influenced by diurnal physiology. Here, we used germ-free and antibiotic-depleted mice to understand how microbiota-dependent oscillations in tryptophan metabolism would alter gut barrier function at baseline and in response to an acute stressor. Cecal metabolomics identified tryptophan metabolism as most responsive to a 15-min acute stressor, while shotgun metagenomics revealed that most bacterial species exhibiting rhythmicity metabolize tryptophan. Our findings highlight that the gastrointestinal response to acute stress is dependent on the time of day and the microbiome, with a signature of stress-induced functional alterations in the ileum and altered tryptophan metabolism in the colon. [Display omitted] •Acute stress alters microbial tryptophan metabolism and impairs gut barrier integrity•Tryptophan-metabolizing bacteria display diurnal rhythmicity•Host tryptophan enzymes display diurnal rhythmicity in the gut•Microbial depletion alters rhythms in gut barrier and host tryptophan metabolism Chronic stress disrupts diurnal rhythmicity and the microbiota-gut-brain axis. Here, Gheorghe et al. show that acute stress alters microbial tryptophan metabolism and gut barrier integrity and that diurnal rhythmicity is a feature of tryptophan-metabolizing bacteria. Normal diurnal rhythms in gut barrier function and host tryptophan metabolism are dependent on the microbiota.