BMAL1 Regulates the Daily Timing of Colitis
Many physiological functions exhibit circadian rhythms: oscillations in biological processes that occur in a 24-hour period. These daily rhythms are maintained through a highly conserved molecular pacemaker known as the circadian clock. Circadian disruption has been proposed to cause increased risk...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.773413/full |
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| author | Zainab Taleb Vania Carmona-Alcocer Kyle Stokes Marta Haireek Huaqing Wang Stephen M. Collins Waliul I. Khan Waliul I. Khan Phillip Karpowicz |
| author_facet | Zainab Taleb Vania Carmona-Alcocer Kyle Stokes Marta Haireek Huaqing Wang Stephen M. Collins Waliul I. Khan Waliul I. Khan Phillip Karpowicz |
| author_sort | Zainab Taleb |
| collection | DOAJ |
| description | Many physiological functions exhibit circadian rhythms: oscillations in biological processes that occur in a 24-hour period. These daily rhythms are maintained through a highly conserved molecular pacemaker known as the circadian clock. Circadian disruption has been proposed to cause increased risk of Inflammatory Bowel Disease (IBD) but the underlying mechanisms remain unclear. Patients with IBD experience chronic inflammation and impaired regeneration of intestinal epithelial cells. Previous animal-based studies have revealed that colitis models of IBD are more severe in mice without a circadian clock but the timing of colitis, and whether its inflammatory and regenerative processes have daily rhythms, remains poorly characterized. We tested circadian disruption using Bmal1-/- mutant mice that have a non-functional circadian clock and thus no circadian rhythms. Dextran Sulfate Sodium (DSS) was used to induce colitis. The disease activity of colitis was found to exhibit time-dependent variation in Bmal1+/+ control mice but is constant and elevated in Bmal1-/- mutants, who exhibit poor recovery. Histological analyses indicate worsened colitis severity in Bmal1-/- mutant colon, and colon infiltration of immune system cells shows a daily rhythm that is lost in the Bmal1-/- mutant. Similarly, epithelial proliferation in the colon has a daily rhythm in Bmal1+/+ controls but not in Bmal1-/- mutants. Our results support a critical role of a functional circadian clock in the colon which drives 24-hour rhythms in inflammation and healing, and whose disruption impairs colitis recovery. This indicates that weakening circadian rhythms not only worsens colitis, but delays healing and should be taken into account in the management of IBD. Recognition of this is important in the management of IBD patients required to do shift work. |
| first_indexed | 2024-12-24T01:50:35Z |
| format | Article |
| id | doaj.art-f91dd03a08294ff8b2eb724aa0e48f41 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-24T01:50:35Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-f91dd03a08294ff8b2eb724aa0e48f412022-12-21T17:21:45ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-02-011210.3389/fcimb.2022.773413773413BMAL1 Regulates the Daily Timing of ColitisZainab Taleb0Vania Carmona-Alcocer1Kyle Stokes2Marta Haireek3Huaqing Wang4Stephen M. Collins5Waliul I. Khan6Waliul I. Khan7Phillip Karpowicz8Department of Biomedical Sciences, University of Windsor, Windsor, ON, CanadaDepartment of Biomedical Sciences, University of Windsor, Windsor, ON, CanadaDepartment of Biomedical Sciences, University of Windsor, Windsor, ON, CanadaDepartment of Biomedical Sciences, University of Windsor, Windsor, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, CanadaFarncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, CanadaFarncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, CanadaDepartment of Biomedical Sciences, University of Windsor, Windsor, ON, CanadaMany physiological functions exhibit circadian rhythms: oscillations in biological processes that occur in a 24-hour period. These daily rhythms are maintained through a highly conserved molecular pacemaker known as the circadian clock. Circadian disruption has been proposed to cause increased risk of Inflammatory Bowel Disease (IBD) but the underlying mechanisms remain unclear. Patients with IBD experience chronic inflammation and impaired regeneration of intestinal epithelial cells. Previous animal-based studies have revealed that colitis models of IBD are more severe in mice without a circadian clock but the timing of colitis, and whether its inflammatory and regenerative processes have daily rhythms, remains poorly characterized. We tested circadian disruption using Bmal1-/- mutant mice that have a non-functional circadian clock and thus no circadian rhythms. Dextran Sulfate Sodium (DSS) was used to induce colitis. The disease activity of colitis was found to exhibit time-dependent variation in Bmal1+/+ control mice but is constant and elevated in Bmal1-/- mutants, who exhibit poor recovery. Histological analyses indicate worsened colitis severity in Bmal1-/- mutant colon, and colon infiltration of immune system cells shows a daily rhythm that is lost in the Bmal1-/- mutant. Similarly, epithelial proliferation in the colon has a daily rhythm in Bmal1+/+ controls but not in Bmal1-/- mutants. Our results support a critical role of a functional circadian clock in the colon which drives 24-hour rhythms in inflammation and healing, and whose disruption impairs colitis recovery. This indicates that weakening circadian rhythms not only worsens colitis, but delays healing and should be taken into account in the management of IBD. Recognition of this is important in the management of IBD patients required to do shift work.https://www.frontiersin.org/articles/10.3389/fcimb.2022.773413/fullcircadian clockinflammatory bowel diseasegastrointestinal tractinflammationregeneration |
| spellingShingle | Zainab Taleb Vania Carmona-Alcocer Kyle Stokes Marta Haireek Huaqing Wang Stephen M. Collins Waliul I. Khan Waliul I. Khan Phillip Karpowicz BMAL1 Regulates the Daily Timing of Colitis Frontiers in Cellular and Infection Microbiology circadian clock inflammatory bowel disease gastrointestinal tract inflammation regeneration |
| title | BMAL1 Regulates the Daily Timing of Colitis |
| title_full | BMAL1 Regulates the Daily Timing of Colitis |
| title_fullStr | BMAL1 Regulates the Daily Timing of Colitis |
| title_full_unstemmed | BMAL1 Regulates the Daily Timing of Colitis |
| title_short | BMAL1 Regulates the Daily Timing of Colitis |
| title_sort | bmal1 regulates the daily timing of colitis |
| topic | circadian clock inflammatory bowel disease gastrointestinal tract inflammation regeneration |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.773413/full |
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