Evidence map›Paper›PMID 36419205›Full record

ArticleMicrobiome2022

Lactobacillus reuteri tryptophan metabolism promotes host susceptibility to CNS autoimmunity.

Theresa L Montgomery, Korin Eckstrom, Katarina H Lile, Sydney Caldwell, Eamonn R Heney, Karolyn G Lahue, Angelo D'Alessandro, Matthew J Wargo, Dimitry N Krementsov

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Microbiome, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 2 pooled it
13.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 175 citations in OpenAlex.

  1. Pooled it
  2. Indoxyl Sulfate and Autism Spectrum Disorder: A Literature Review.International journal of molecular sciences · 2024
    Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Article
  8. Review
  9. Tobacco smoking disrupts bile acid and tryptophan metabolism in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Article
  10. Nutrient control enables metabolic reconstruction ofbioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. Article
  13. Review
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  16. Article
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  20. Article

47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Theresa L MontgomeryDepartment of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05401, USA.
Korin EckstromDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05401, USA.
Katarina H LileDepartment of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05401, USA.
Sydney CaldwellDepartment of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05401, USA.
Eamonn R HeneyDepartment of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05401, USA.
Karolyn G LahueDepartment of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05401, USA.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO, 80045, USA.
Matthew J WargoDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05401, USA.
Dimitry N KrementsovDepartment of Biomedical and Health Sciences, University of Vermont, Burlington, VT, 05401, USA. dimitry.krementsov@uvm.edu.
University of Vermont · USUniversity of Colorado Anschutz Medical Campus · US

Funding

SUBSTRATE SPECIFICITY OF THE BER OXIDATIVE DNA GLYCOSYLASESP01CA098993 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI LEE, ANDREA J · 2004 to 2021
$25.9M
National Gnotobiotic Rodent Resource CenterP40OD010995 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ryan B Sartor · 2012 to 2026
$9.7M
Vermont Immunology/Infectious Diseases CenterP30GM118228 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BUDD, RALPH C · 2016 to 2021
$6.8M
Vermont Immunology/Infectious Diseases Training GrantT32AI055402 · NIAID · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI GARY E WARD · 2005 to 2026
$2.7M
Interactions Between Host Genetics and the Gut Microbiome in CNS AutoimmunityR01NS097596 · NINDS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI KREMENTSOV, DIMITRY N · 2017 to 2021
$1.7M
Acquisition of a new Flow CytometerS10OD026843 · OD · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BOYSON, JONATHAN E · 2019 to 2019
$204k
Mechanisms Underlying Regulation of Susceptibility to CNS Autoimmunity by Commensal Lactobacillus SpeciesF31NS120381 · NINDS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI MONTGOMERY, THERESA LYNN · 2021 to 2022
$30k
NCI NIH HHS P01 CA098993NIAID NIH HHS T32 AI055402NIGMS NIH HHS P30 GM118228NIH HHS P40 OD010995NIH HHS S10 OD026843NINDS NIH HHS F31 NS120381NINDS NIH HHS R01 NS097596
6 · The paper itself

Abstract

backgroundDysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links between this apparent metabolic rewiring and individual constituents of the gut microbiota remains challenging. We and others have previously shown that colonization with the gut commensal and putative probiotic species, Lactobacillus reuteri, unexpectedly enhances host susceptibility to experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. To identify underlying mechanisms, we characterized the genome of commensal L. reuteri isolates, coupled with in vitro and in vivo metabolomic profiling, modulation of dietary substrates, and gut microbiota manipulation.

resultsThe enzymes necessary to metabolize dietary tryptophan into immunomodulatory indole derivatives were enriched in the L. reuteri genomes, including araT, fldH, and amiE. Moreover, metabolite profiling of L. reuteri monocultures and serum of L. reuteri-colonized mice revealed a depletion of kynurenines and production of a wide array of known and novel tryptophan-derived aryl hydrocarbon receptor (AhR) agonists and antagonists, including indole acetate, indole-3-glyoxylic acid, tryptamine, p-cresol, and diverse imidazole derivatives. Functionally, dietary tryptophan was required for L. reuteri-dependent EAE exacerbation, while depletion of dietary tryptophan suppressed disease activity and inflammatory T cell responses in the CNS. Mechanistically, L. reuteri tryptophan-derived metabolites activated the AhR and enhanced T cell production of IL-17.

conclusionsOur data suggests that tryptophan metabolism by gut commensals, such as the putative probiotic species L. reuteri, can unexpectedly enhance autoimmunity, inducing broad shifts in the metabolome and immunological repertoire. Video Abstract.

Indexed as

Limosilactobacillus reuteriMultiple SclerosisAnimalsAutoimmunityIndolesMiceTryptophanIndolesTryptophanAryl hydrocarbon receptor (AhR)Experimental autoimmune encephalomyelitis (EAE)L. reuteriMicrobiomeMicrobiotaMultiple sclerosisTryptophan

Identifiers

PMID36419205
PMCPMC9685921
OpenAlexW4309884182

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.