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Food restriction heals darkness-related second brain inflammation

Cellular & Molecular Immunology (2024)Cite this article

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Modern lifestyle-related circadian disruption has been closely linked to several pathologies, including inflammatory bowel diseases (IBD) such as colitis (Fig. 1B). It can alter immune responses and shift a healthy intestinal microbiota into a pathological one, facilitating the onset of colitis [4]. Moreover, the intestines, otherwise known as the “second brain,” contain about the same number of neurons as the spinal cord and aid in regulating physical and mental health, highlighting the intricate connections between our digestive system and overall well-being [5, 6].

Recently, Niu et al. reported a close relationship between colon inflammation and constant darkness-induced disruption of the intestinal circadian clock (Fig. 1B, C), specifically involving a gene named brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1). Their study revealed that night-time restricted feeding (nRF) alleviates this condition by promoting specific immune responses that foster a healthy colonic microbiota, which was validated by mechanistic fecal transplantation experiments [7].

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Fig. 1

References

  1. Koronowski KB, Kinouchi K, Welz PS, Smith JG, Zinna VM, Shi J, et al. Defining the Independence of the Liver Circadian Clock. Cell. 2019;177:1448–62.e14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Welz PS, Zinna VM, Symeonidi A, Koronowski KB, Kinouchi K, Smith JG, et al. BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis. Cell. 2019;177:1436–47.e12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yang CH, Hwang CF, Chuang JH, Lian WS, Wang FS, Huang EI, et al. Constant Light Dysregulates Cochlear Circadian Clock and Exacerbates Noise-Induced Hearing Loss. Int J Mol Sci. 2020;21:7535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schneider KM, Blank N, Alvarez Y, Thum K, Lundgren P, Litichevskiy L, et al. The enteric nervous system relays psychological stress to intestinal inflammation. Cell. 2023;186:2823–38.e20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hoogerwerf WA, Hellmich HL, Cornélissen G, Halberg F, Shahinian VB, Bostwick J, et al. Clock gene expression in the murine gastrointestinal tract: endogenous rhythmicity and effects of a feeding regimen. Gastroenterology. 2007;133:1250–60.

    Article  CAS  PubMed  Google Scholar 

  6. Drokhlyansky E, Smillie CS, Van Wittenberghe N, Ericsson M, Griffin GK, Eraslan G, et al. The Human and Mouse Enteric Nervous System at Single-Cell Resolution. Cell. 2020;182:1606–22.e23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Niu Y, Heddes M, Altaha B, Birkner M, Kleigrewe K, Meng C, et al. Targeting the intestinal circadian clock by meal timing ameliorates gastrointestinal inflammation. Cell Mol Immunol. 2024;21:842–55.

  8. Ono D, Honma S, Nakajima Y, Kuroda S, Enoki R, Honma KI. Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus in parallel with behavioral outputs. Proc Natl Acad Sci USA. 2017;114:E3699–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abe YO, Yoshitane H, Kim DW, Kawakami S, Koebis M, Nakao K, et al. Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals. Nat Commun. 2022;13:4652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Curtis AM, Fagundes CT, Yang G, Palsson-McDermott EM, Wochal P, McGettrick AF, et al. Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1. Proc Natl Acad Sci USA. 2015;112:7231–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhai Q, Zeng Y, Gu Y, Li Z, Zhang T, Yuan B, et al. Time-restricted feeding entrains long-term behavioral changes through the IGF2-KCC2 pathway. iScience. 2022;25:104267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. University of Toronto, Department of Pharmacology and Toxicology, 1 King’s College Cir, Toronto, ON, M5S 1A8, Canada

    Vinicius Kannen

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Kannen, V. Food restriction heals darkness-related second brain inflammation. Cell Mol Immunol (2024). https://doi.org/10.1038/s41423-024-01196-0

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