Dataset Information

Abnormal Food Timing Promotes Alcohol-Associated Dysbiosis and Colon Carcinogenesis Pathways.

ABSTRACT: Background: Alcohol consumption is an established risk factor for colorectal cancer (CRC). Identifying cofactor(s) that modulate the effect of alcohol on colon inflammation and carcinogenesis could help risk stratification for CRC. Disruption of circadian rhythm by light/dark shift promotes alcohol-induced colonic inflammation and cancer. More recently, we found that abnormal food timing causes circadian rhythm disruption and promotes alcohol associated colon carcinogenesis. In this study, we examined the interaction of wrong-time feeding (WTF) and alcohol on CRC-related pathways, in relation to changes in microbial community structure. Methods: Polyposis mice (TS4Cre ×cAPC ?468) underwent four conditions: alcohol or water and feeding during the light (wrong-time fed/WTF) or during the dark (right-time fed). Colonic cecum mucosal gene expression was analyzed by RNA-seq. Microbiota 16S ribosomal RNA sequencing analysis was used to examine colonic feces. Modeling was used to estimate the extent of the gene expression changes that could be related to the changes in the colonic microbial composition. Results: The circadian rhythm pathway was the most altered pathway by the WTF treatment, indicating that WTF is disruptive to the colonic circadian rhythm. Pathway analysis revealed interaction of WTF with alcohol in dysregulating pathways related to colon carcinogenesis. Similarly, the interaction of alcohol and WTF was detected at multiple parameters of the colonic microbiota including ? and ? diversity, as well as the community structure. Our modeling revealed that almost a third of total gene alterations induced by our treatments could be related to alterations in the abundance of the microbial taxa. Conclusion: These data support the promoting effect of abnormal food timing alcohol-associated CRC-related pathways in the colon and suggest colon dysbiosis as a targetable mechanism.

SUBMITTER: Bishehsari F

PROVIDER: S-EPMC7396506 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Abnormal Food Timing Promotes Alcohol-Associated Dysbiosis and Colon Carcinogenesis Pathways.

Bishehsari Faraz F Moossavi Shirin S Engen Phillip A PA Liu Xiaohan X Zhang Yue Y

Frontiers in oncology 20200717

<b>Background:</b> Alcohol consumption is an established risk factor for colorectal cancer (CRC). Identifying cofactor(s) that modulate the effect of alcohol on colon inflammation and carcinogenesis could help risk stratification for CRC. Disruption of circadian rhythm by light/dark shift promotes alcohol-induced colonic inflammation and cancer. More recently, we found that abnormal food timing causes circadian rhythm disruption and promotes alcohol associated colon carcinogenesis. In this study ...[more]

PMID: 32850307

Similar Datasets

Project description:Background & aimsAlcohol 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.MethodsThe 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.ResultsEating 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.ConclusionsAbnormal 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.

Dataset Information

Abnormal Food Timing Promotes Alcohol-Associated Dysbiosis and Colon Carcinogenesis Pathways.

Publications

Abnormal Food Timing Promotes Alcohol-Associated Dysbiosis and Colon Carcinogenesis Pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets