Evidence map›Paper›PMID 27411368›Full record

ArticleGut2017

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism.

I Oancea, R Movva, I Das, D Aguirre de Cárcer, V Schreiber, Y Yang, A Purdon, B Harrington, M Proctor, R Wang and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
6.3field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 79 citations in OpenAlex.

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  10. Novel Techniques and Models for Studying the Role of the Gut Microbiota in Drug Metabolism.European journal of drug metabolism and pharmacokinetics · 2024
    Review
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  20. Personalized medicine to implementation science: Thiopurines set for the leap.JGH open : an open access journal of gastroenterology and hepatology · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

I OanceaImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
R MovvaImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
I DasImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
D Aguirre de CárcerDivision of Livestock Industries, CSIRO Preventative Health National Research Flagship, Brisbane, Queensland, Australia.
V SchreiberImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
Y YangImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
A PurdonImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
B HarringtonImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
M ProctorImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
R WangImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
Y ShengImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
M LobbInflammatory Diseases Biology & Therapeutics Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
R LourieImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
P Ó CuívTranslational Research Institute, Woolloongabba, Queensland, Australia.
J A DuleyDivision of Livestock Industries, CSIRO Preventative Health National Research Flagship, Brisbane, Queensland, Australia.
J BegunImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
T H J FlorinImmunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
University of Queensland · AUMater Research · AUTranslational Research Institute · AUCommonwealth Scientific and Industrial Research Organisation · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveMercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG).

designC57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed.

resultsOral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt

conclusionsTreatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation.

Indexed as

Administration, OralAdministration, RectalAnimalsAutophagyBacteroides thetaiotaomicronCells, CulturedColitisColonCytokinesDextran SulfateEnterococcus faecalisEpithelial CellsEscherichia coliFemaleFibroblastsGastrointestinal MicrobiomeCytokinesDextran SulfateHypoxanthine PhosphoribosyltransferaseImmunosuppressive AgentsMercaptopurineMuc2 protein, mouseMucin-2RNA, MessengerThioguanineAZATHIOPRINECOLONIC BACTERIADRUG METABOLISMIBD MODELS

Identifiers

PMID27411368
PMCPMC5256391
OpenAlexW2336923290

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.