Evidence map›Paper›PMID 34086699›Full record

ArticlePloS one2021

Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.

Laura Tran, Sarah B Jochum, Maliha Shaikh, Sherry Wilber, Lijuan Zhang, Dana M Hayden, Christopher B Forsyth, Robin M Voigt, Faraz Bishehsari, Ali Keshavarzian and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  7. The circadian rhythm as therapeutic target in inflammatory bowel disease.Journal of the Canadian Association of Gastroenterology · 2025
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  19. Circadian rhythms in colonic function.Frontiers in physiology · 2023
    Review
  20. Article
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

11 authors at 1 institution in 1 country.

Laura TranRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.ORCID 0000-0002-4428-053X
Sarah B JochumDepartment of Surgery, Rush University Medical Center, Chicago, Illinois, United States of America.
Maliha ShaikhRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Sherry WilberRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.ORCID 0000-0002-2117-4670
Lijuan ZhangRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Dana M HaydenDepartment of Surgery, Rush University Medical Center, Chicago, Illinois, United States of America.
Christopher B ForsythRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Robin M VoigtRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Faraz BishehsariRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Ali KeshavarzianRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Garth R SwansonRush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, United States of America.
Rush University Medical Center · US

Funding

Center for Circadian Rhythms and Alcohol-Induced Tissue DamageR24AA026801 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI ALI KESHAVARZIAN · 2019 to 2026
$4.5M
Abnormal Food Timing and Circadian Dyssynchrony in Alcohol Induced Colon CarcinogenesisK23AA025387 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI BISHEHSARI, FARAZ · 2018 to 2022
$945k
NIAAA NIH HHS K23 AA025387NIAAA NIH HHS R24 AA026801
6 · The paper itself

Abstract

backgroundPhysiological circadian rhythms (CRs) are complex processes with 24-hour oscillations that regulate diverse biological functions. Chronic weekly light/dark (LD) shifting (CR disruption; CRD) in mice results in colonic hyperpermeability. However, the mechanisms behind this phenomenon are incompletely understood. One potential innovative in vitro method to study colonic CRs are colon organoids. The goals of this study were to utilize circadian clock gene Per2 luciferase reporter (Per2::Luc) mice to measure the effects of chronic LD shifting on colonic tissue circadian rhythmicity ex vivo and to determine if organoids made from shifted mice colons recapitulate the in vivo phenotype.

methodsNon-shifted (NS) and shifted (S) BL6 Per2::Luc mice were compared after a 22-week experiment. NS mice had a standard 12h light/12h dark LD cycle throughout. S mice alternated 12h LD patterns weekly, with light from 6am-6pm one week followed by shifting light to 6pm-6am the next week for 22 weeks. Mice were tested for intestinal permeability while colon tissue and organoids were examined for CRs of bioluminescence and proteins of barrier function and cell fate.

resultsThere was no absolute difference in NS vs. S 24h circadian period or phase. However, chronic LD shifting caused Per2::Luc S mice colon tissue to exhibit significantly greater variability in both the period and phase of Per2::Luc rhythms than NS mice colon tissue and organoids. Chronic LD shifting also resulted in increased colonic permeability of the Per2::Luc mice as well as decreased protein markers of intestinal permeability in colonic tissue and organoids from shifted Per2:Luc mice.

conclusionsOur studies support a model in which chronic central circadian disruption by LD shifting alters the circadian phenotype of the colon tissue and results in colon leakiness and loss of colonic barrier function. These CRD-related changes are stably expressed in colon stem cell derived organoids from CRD mice.

Indexed as

AnimalsCircadian ClocksCircadian RhythmColonHumansIntestinesLuciferasesMaleMiceMice, Inbred C57BLMotor ActivityPeriod Circadian ProteinsPermeabilityPhotoperiodSuprachiasmatic NucleusLuciferasesPeriod Circadian Proteins

Identifiers

PMID34086699
PMCPMC8177509
OpenAlexW3164432804

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.