Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-021-99845-1
Title: Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature
Authors: Brydges, Christopher R.
Fiehn, Oliver
Mayberg, Helen S.
Schreiber, Henry
Dehkordi, Siamak Mahmoudian
Bhattacharyya, Sudeepa
Cha, Jungho
Choi, Ki Sueng
Craighead, W. Edward
Krishnan, Ranga R.
Rush, A. John 
Dunlop, Boadie W.
Kaddurah-Daouk, Rima
Penninx, Brenda
Binder, Elizabeth
Kastenmüller, Gabi
Arnold, Matthias
Nevado-Helgado, Alejo
Blach, Colette
Milaneschi, Yuri
Knauer-Arloth, Janine
Jansen, Rich
Mook-Kanamori, Dennis
Han, Xianlin
Baillie, Rebecca
Rinaldo, Piero
Issue Date: 25-Oct-2021
Publisher: Nature Research
Citation: Brydges, Christopher R., Fiehn, Oliver, Mayberg, Helen S., Schreiber, Henry, Dehkordi, Siamak Mahmoudian, Bhattacharyya, Sudeepa, Cha, Jungho, Choi, Ki Sueng, Craighead, W. Edward, Krishnan, Ranga R., Rush, A. John, Dunlop, Boadie W., Kaddurah-Daouk, Rima, Penninx, Brenda, Binder, Elizabeth, Kastenmüller, Gabi, Arnold, Matthias, Nevado-Helgado, Alejo, Blach, Colette, Milaneschi, Yuri, Knauer-Arloth, Janine, Jansen, Rich, Mook-Kanamori, Dennis, Han, Xianlin, Baillie, Rebecca, Rinaldo, Piero (2021-10-25). Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature. Scientific Reports 11 (1) : 21011. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-021-99845-1
Rights: Attribution 4.0 International
Abstract: It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite’s effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies. Clinical trial NCT00360399 “Predictors of Antidepressant Treatment Response: The Emory CIDAR” https://clinicaltrials.gov/ct2/show/NCT00360399. © 2021, The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/232700
ISSN: 2045-2322
DOI: 10.1038/s41598-021-99845-1
Rights: Attribution 4.0 International
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