The microbiota drives diurnal rhythms in tryptophan metabolism in the stressed gut
Cassandra E. Gheorghe,
Sarah-Jane Leigh,
Gabriel S.S. Tofani,
Thomaz F.S. Bastiaanssen,
Joshua M. Lyte,
Elisa Gardellin,
Ashokkumar Govindan,
Conall Strain,
Sonia Martinez-Herrero,
Michael S. Goodson,
Nancy Kelley-Loughnane,
John F. Cryan,
Gerard Clarke
Affiliations
Cassandra E. Gheorghe
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Sarah-Jane Leigh
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Gabriel S.S. Tofani
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Thomaz F.S. Bastiaanssen
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Joshua M. Lyte
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Elisa Gardellin
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 CY82 Cork, Ireland
Ashokkumar Govindan
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy Co, P61 C996 Cork, Ireland
Conall Strain
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy Co, P61 C996 Cork, Ireland
Sonia Martinez-Herrero
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Michael S. Goodson
711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH 45324, USA
Nancy Kelley-Loughnane
711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH 45324, USA
John F. Cryan
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, T12 CY82 Cork, Ireland
Gerard Clarke
APC Microbiome Ireland, University College Cork, T12 CY82 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, T12 CY82 Cork, Ireland; Corresponding author
Summary: 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.
