Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis

Faraz Bishehsari; Phillip A. Engen; Robin M. Voigt; Garth Swanson; Maliha Shaikh; Sherry Wilber; Ankur Naqib; Stefan J. Green; Brandon Shetuni; Christopher B. Forsyth; Abdulrahman Saadalla; Abu Osman; Bruce R. Hamaker; Ali Keshavarzian; Khashayarsha Khazaie

doi:10.1016/j.jcmgh.2019.10.011

Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis

Faraz Bishehsari, Phillip A. Engen, Robin M. Voigt, Garth Swanson, Maliha Shaikh, Sherry Wilber, Ankur Naqib, Stefan J. Green, Brandon Shetuni, Christopher B. Forsyth, Abdulrahman Saadalla, Abu Osman, Bruce R. Hamaker, Ali Keshavarzian, Khashayarsha Khazaie

Allergy, Asthma and Clinical Immunology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background & Aims: Alcohol intake with circadian rhythm disruption (CRD) increases colon cancer risk. We hypothesized that eating during or around physiologic rest time, a common habit in modern society, causes CRD and investigated the mechanisms by which it promotes alcohol-associated colon carcinogenesis. Methods: The effect of feeding time on CRD was assessed using B6 mice expressing a fusion protein of PERIOD2 and LUCIFERASE (PER2::LUC) were used to model colon polyposis and to assess the effects of feeding schedules, alcohol consumption, and prebiotic treatment on microbiota composition, short-chain fatty acid levels, colon inflammation, and cancer risk. The relationship between butyrate signaling and a proinflammatory profile was assessed by inactivating the butyrate receptor GPR109A. Results: Eating at rest (wrong-time eating [WTE]) shifted the phase of the colon rhythm in PER2::LUC mice. In TS4Cre × APC^lox468 mice, a combination of WTE and alcohol exposure (WTE + alcohol) decreased the levels of short-chain fatty acid–producing bacteria and of butyrate, reduced colonic densities of regulatory T cells, induced a proinflammatory profile characterized by hyperpermeability and an increased mucosal T-helper cell 17/regulatory T cell ratio, and promoted colorectal cancer. Prebiotic treatment improved the mucosal inflammatory profile and attenuated inflammation and cancer. WTE + alcohol–induced polyposis was associated with increased signal transducer and activator of transcription 3 expression. Decreased butyrate signaling activated the epithelial signal transducer and activator of transcription 3 in vitro. The relationship between butyrate signaling and a proinflammatory profile was confirmed in human colorectal cancers using The Cancer Genome Atlas. Conclusions: Abnormal timing of food intake caused CRD and interacts with alcohol consumption to promote colon carcinogenesis by inducing a protumorigenic inflammatory profile driven by changes in the colon microbiota and butyrate signaling. Accession number of repository for microbiota sequence data: raw FASTQ data were deposited in the NCBI Sequence Read Archive under project PRJNA523141.

Original language	English (US)
Pages (from-to)	219-237
Number of pages	19
Journal	CMGH
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.jcmgh.2019.10.011
State	Published - 2020

Keywords

Alcohol
Butyrate
Circadian
Colon Cancer
Food Time
Microbiota

ASJC Scopus subject areas

Hepatology
Gastroenterology

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10.1016/j.jcmgh.2019.10.011

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Bishehsari, F., Engen, P. A., Voigt, R. M., Swanson, G., Shaikh, M., Wilber, S., Naqib, A., Green, S. J., Shetuni, B., Forsyth, C. B., Saadalla, A., Osman, A., Hamaker, B. R., Keshavarzian, A., & Khazaie, K. (2020). Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis. CMGH, 9(2), 219-237. https://doi.org/10.1016/j.jcmgh.2019.10.011

Bishehsari, F, Engen, PA, Voigt, RM, Swanson, G, Shaikh, M, Wilber, S, Naqib, A, Green, SJ, Shetuni, B, Forsyth, CB, Saadalla, A, Osman, A, Hamaker, BR, Keshavarzian, A & Khazaie, K 2020, 'Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis', CMGH, vol. 9, no. 2, pp. 219-237. https://doi.org/10.1016/j.jcmgh.2019.10.011

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title = "Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis",

abstract = "Background & Aims: Alcohol intake with circadian rhythm disruption (CRD) increases colon cancer risk. We hypothesized that eating during or around physiologic rest time, a common habit in modern society, causes CRD and investigated the mechanisms by which it promotes alcohol-associated colon carcinogenesis. Methods: The effect of feeding time on CRD was assessed using B6 mice expressing a fusion protein of PERIOD2 and LUCIFERASE (PER2::LUC) were used to model colon polyposis and to assess the effects of feeding schedules, alcohol consumption, and prebiotic treatment on microbiota composition, short-chain fatty acid levels, colon inflammation, and cancer risk. The relationship between butyrate signaling and a proinflammatory profile was assessed by inactivating the butyrate receptor GPR109A. Results: Eating at rest (wrong-time eating [WTE]) shifted the phase of the colon rhythm in PER2::LUC mice. In TS4Cre × APClox468 mice, a combination of WTE and alcohol exposure (WTE + alcohol) decreased the levels of short-chain fatty acid–producing bacteria and of butyrate, reduced colonic densities of regulatory T cells, induced a proinflammatory profile characterized by hyperpermeability and an increased mucosal T-helper cell 17/regulatory T cell ratio, and promoted colorectal cancer. Prebiotic treatment improved the mucosal inflammatory profile and attenuated inflammation and cancer. WTE + alcohol–induced polyposis was associated with increased signal transducer and activator of transcription 3 expression. Decreased butyrate signaling activated the epithelial signal transducer and activator of transcription 3 in vitro. The relationship between butyrate signaling and a proinflammatory profile was confirmed in human colorectal cancers using The Cancer Genome Atlas. Conclusions: Abnormal timing of food intake caused CRD and interacts with alcohol consumption to promote colon carcinogenesis by inducing a protumorigenic inflammatory profile driven by changes in the colon microbiota and butyrate signaling. Accession number of repository for microbiota sequence data: raw FASTQ data were deposited in the NCBI Sequence Read Archive under project PRJNA523141.",

keywords = "Alcohol, Butyrate, Circadian, Colon Cancer, Food Time, Microbiota",

author = "Faraz Bishehsari and Engen, {Phillip A.} and Voigt, {Robin M.} and Garth Swanson and Maliha Shaikh and Sherry Wilber and Ankur Naqib and Green, {Stefan J.} and Brandon Shetuni and Forsyth, {Christopher B.} and Abdulrahman Saadalla and Abu Osman and Hamaker, {Bruce R.} and Ali Keshavarzian and Khashayarsha Khazaie",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

doi = "10.1016/j.jcmgh.2019.10.011",

language = "English (US)",

volume = "9",

pages = "219--237",

journal = "CMGH",

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T1 - Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis

AU - Bishehsari, Faraz

AU - Engen, Phillip A.

AU - Voigt, Robin M.

AU - Swanson, Garth

AU - Shaikh, Maliha

AU - Wilber, Sherry

AU - Naqib, Ankur

AU - Green, Stefan J.

AU - Shetuni, Brandon

AU - Forsyth, Christopher B.

AU - Saadalla, Abdulrahman

AU - Osman, Abu

AU - Hamaker, Bruce R.

AU - Keshavarzian, Ali

AU - Khazaie, Khashayarsha

PY - 2020

Y1 - 2020

N2 - Background & Aims: Alcohol intake with circadian rhythm disruption (CRD) increases colon cancer risk. We hypothesized that eating during or around physiologic rest time, a common habit in modern society, causes CRD and investigated the mechanisms by which it promotes alcohol-associated colon carcinogenesis. Methods: The effect of feeding time on CRD was assessed using B6 mice expressing a fusion protein of PERIOD2 and LUCIFERASE (PER2::LUC) were used to model colon polyposis and to assess the effects of feeding schedules, alcohol consumption, and prebiotic treatment on microbiota composition, short-chain fatty acid levels, colon inflammation, and cancer risk. The relationship between butyrate signaling and a proinflammatory profile was assessed by inactivating the butyrate receptor GPR109A. Results: Eating at rest (wrong-time eating [WTE]) shifted the phase of the colon rhythm in PER2::LUC mice. In TS4Cre × APClox468 mice, a combination of WTE and alcohol exposure (WTE + alcohol) decreased the levels of short-chain fatty acid–producing bacteria and of butyrate, reduced colonic densities of regulatory T cells, induced a proinflammatory profile characterized by hyperpermeability and an increased mucosal T-helper cell 17/regulatory T cell ratio, and promoted colorectal cancer. Prebiotic treatment improved the mucosal inflammatory profile and attenuated inflammation and cancer. WTE + alcohol–induced polyposis was associated with increased signal transducer and activator of transcription 3 expression. Decreased butyrate signaling activated the epithelial signal transducer and activator of transcription 3 in vitro. The relationship between butyrate signaling and a proinflammatory profile was confirmed in human colorectal cancers using The Cancer Genome Atlas. Conclusions: Abnormal timing of food intake caused CRD and interacts with alcohol consumption to promote colon carcinogenesis by inducing a protumorigenic inflammatory profile driven by changes in the colon microbiota and butyrate signaling. Accession number of repository for microbiota sequence data: raw FASTQ data were deposited in the NCBI Sequence Read Archive under project PRJNA523141.

AB - Background & Aims: Alcohol intake with circadian rhythm disruption (CRD) increases colon cancer risk. We hypothesized that eating during or around physiologic rest time, a common habit in modern society, causes CRD and investigated the mechanisms by which it promotes alcohol-associated colon carcinogenesis. Methods: The effect of feeding time on CRD was assessed using B6 mice expressing a fusion protein of PERIOD2 and LUCIFERASE (PER2::LUC) were used to model colon polyposis and to assess the effects of feeding schedules, alcohol consumption, and prebiotic treatment on microbiota composition, short-chain fatty acid levels, colon inflammation, and cancer risk. The relationship between butyrate signaling and a proinflammatory profile was assessed by inactivating the butyrate receptor GPR109A. Results: Eating at rest (wrong-time eating [WTE]) shifted the phase of the colon rhythm in PER2::LUC mice. In TS4Cre × APClox468 mice, a combination of WTE and alcohol exposure (WTE + alcohol) decreased the levels of short-chain fatty acid–producing bacteria and of butyrate, reduced colonic densities of regulatory T cells, induced a proinflammatory profile characterized by hyperpermeability and an increased mucosal T-helper cell 17/regulatory T cell ratio, and promoted colorectal cancer. Prebiotic treatment improved the mucosal inflammatory profile and attenuated inflammation and cancer. WTE + alcohol–induced polyposis was associated with increased signal transducer and activator of transcription 3 expression. Decreased butyrate signaling activated the epithelial signal transducer and activator of transcription 3 in vitro. The relationship between butyrate signaling and a proinflammatory profile was confirmed in human colorectal cancers using The Cancer Genome Atlas. Conclusions: Abnormal timing of food intake caused CRD and interacts with alcohol consumption to promote colon carcinogenesis by inducing a protumorigenic inflammatory profile driven by changes in the colon microbiota and butyrate signaling. Accession number of repository for microbiota sequence data: raw FASTQ data were deposited in the NCBI Sequence Read Archive under project PRJNA523141.

KW - Alcohol

KW - Butyrate

KW - Circadian

KW - Colon Cancer

KW - Food Time

KW - Microbiota

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Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis

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