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Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.

Publication ,  Journal Article
Brydges, CR; Fiehn, O; Mayberg, HS; Schreiber, H; Dehkordi, SM; Bhattacharyya, S; Cha, J; Choi, KS; Craighead, WE; Krishnan, RR; Rush, AJ ...
Published in: Sci Rep
October 25, 2021

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 .

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 25, 2021

Volume

11

Issue

1

Start / End Page

21011

Location

England

Related Subject Headings

  • Young Adult
  • Uremic Toxins
  • Symptom Assessment
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Metabolic Networks and Pathways
  • Male
  • Magnetic Resonance Imaging
  • Indican
 

Citation

APA
Chicago
ICMJE
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Brydges, C. R., Fiehn, O., Mayberg, H. S., Schreiber, H., Dehkordi, S. M., Bhattacharyya, S., … Mood Disorders Precision Medicine Consortium, . (2021). Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature. Sci Rep, 11(1), 21011. https://doi.org/10.1038/s41598-021-99845-1
Brydges, Christopher R., Oliver Fiehn, Helen S. Mayberg, Henry Schreiber, Siamak Mahmoudian Dehkordi, Sudeepa Bhattacharyya, Jungho Cha, et al. “Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.Sci Rep 11, no. 1 (October 25, 2021): 21011. https://doi.org/10.1038/s41598-021-99845-1.
Brydges CR, Fiehn O, Mayberg HS, Schreiber H, Dehkordi SM, Bhattacharyya S, et al. Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature. Sci Rep. 2021 Oct 25;11(1):21011.
Brydges, Christopher R., et al. “Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.Sci Rep, vol. 11, no. 1, Oct. 2021, p. 21011. Pubmed, doi:10.1038/s41598-021-99845-1.
Brydges CR, Fiehn O, Mayberg HS, Schreiber H, Dehkordi SM, Bhattacharyya S, Cha J, Choi KS, Craighead WE, Krishnan RR, Rush AJ, Dunlop BW, Kaddurah-Daouk R, Mood Disorders Precision Medicine Consortium. Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature. Sci Rep. 2021 Oct 25;11(1):21011.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 25, 2021

Volume

11

Issue

1

Start / End Page

21011

Location

England

Related Subject Headings

  • Young Adult
  • Uremic Toxins
  • Symptom Assessment
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Metabolic Networks and Pathways
  • Male
  • Magnetic Resonance Imaging
  • Indican