Dataset Information

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.

SUBMITTER: Bishehsari F

PROVIDER: S-EPMC6957855 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Bishehsari Faraz F Engen Phillip A PA Voigt Robin M RM Swanson Garth G Shaikh Maliha M Wilber Sherry S Naqib Ankur A Green Stefan J SJ Shetuni Brandon B Forsyth Christopher B CB Saadalla Abdulrahman A Osman Abu A Hamaker Bruce R BR Keshavarzian Ali A Khazaie Khashayarsha K

Cellular and molecular gastroenterology and hepatology 20191102 2

<h4>Background & aims</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31689559

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Project description: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.

Project description:Restrained Eating, i.e. the tendency to restrict dietary intake to control body-weight, often emerges during adolescence and may result in changes in circadian eating patterns.The objective of the present investigation was to determine the cross-sectional relevance of restrained eating for characteristics of circadian eating pattern in adolescents and whether changes in restrained eating are accompanied by concurrent changes in circadian eating pattern over the course of adolescence.Two questionnaires assessing restrained eating (Score 0-30) with parallel 3-day weighed dietary records from two different time points were available from 209 (?:101, ?:108) 11-18 year old adolescents of the DONALD study. Mixed linear regression models were used to analyze whether restrained eating was associated with eating occasion frequency, snack frequency and morning and evening energy intake [in % of daily energy intake, %E]. Linear regression models were used to examine whether changes in restrained eating were associated with changes in the mentioned variables.Among girls, greater restrained eating was cross-sectionally associated with higher morning energy intake (p = 0.03). Further, there was a tendency towards lower evening energy intake with higher levels of restrained eating for the whole sample (p = 0.06). No cross-sectional associations were found with eating occasion or snack frequency. Each one-point increase in restrained eating during adolescence was related to a concurrent decrease in eating occasion frequency by 0.04 (95% CI -0.08; -0.01, p = 0.02) and in evening energy intake by 0.36%E (95% CI -0.70; -0.03, p = 0.04). A tendency towards decreasing snack frequency with increasing restrained eating was observed (? = -0.03, 95% CI -0.07; 0.00, p = 0.07). No association was found between changes in restrained eating and concurrent changes in morning energy intake.We found indications for cross-sectional and prospective associations between restrained eating and chronobiological aspects of food intake in adolescents. Our results suggest that restrained eating should be considered a relevant determinant of circadian eating patterns.

Project description:BackgroundAlcoholic liver disease (ALD) is commonly associated with intestinal permeability. An unanswered question is why only a subset of heavy alcohol drinkers develop endotoxemia. Recent studies suggest that circadian disruption is the susceptibility factor for alcohol-induced gut leakiness to endotoxins. The circadian protein PER2 is increased after exposure to alcohol and siRNA knockdown of PER2 in vitro blocks alcohol-induced intestinal barrier dysfunction. We have shown that blocking CYP2E1 (i.e., important for alcohol metabolism) with siRNA inhibits the alcohol-induced increase in PER2 and suggesting that oxidative stress may mediate alcohol-induced increase in PER2 in intestinal epithelial cells. The aim of this study was to elucidate whether a mechanism incited by alcohol-derived oxidative stress mediates the transcriptional induction of PER2 and subsequent intestinal hyperpermeability.MethodsCaco-2 cells were exposed to 0.2% alcohol with or without pretreatment with modulators of oxidative stress or PKA activity. Permeability of the Caco-2 monolayer was assessed by transepithelial electrical resistance. Protein expression was measured by Western blot and mRNA with real-time polymerase chain reaction. Wild-type C57BL/6J mice were fed with alcohol diet (29% of total calories, 4.5% v/v) for 8 weeks. Western blot was used to analyze PER2 expression in mouse proximal colon tissue.ResultsAlcohol increased oxidative stress, caused Caco-2 cell monolayer dysfunction, and increased levels of the circadian clock proteins PER2 and CLOCK. These effects were mitigated by pretreatment of Caco-2 cells with an antioxidant scavenger. Alcohol-derived oxidative stress activated cAMP response element-binding (CREB) via the PKA pathway and increased PER2 mRNA and protein. Inhibiting CREB prevented the increase in PER2 and Caco-2 cell monolayer hyperpermeability.ConclusionsTaken together, these data suggest that strategies to reduce alcohol-induced oxidative stress may alleviate alcohol-mediated circadian disruption and intestinal leakiness, critical drivers of ALD.

Project description:BackgroundEmotional eating (EE) is one of the most significant symptoms of various eating disorders. It has been difficult to collect a large amount of behavioral data on EE; therefore, only partial studies of this symptom have been conducted. To provide adequate support for online social media users with symptoms of EE, we must understand their behavior patterns to design a sophisticated personalized support system (PSS).ObjectiveThis study aimed to analyze the behavior patterns of emotional eaters as the first step to designing a personalized intervention system.MethodsThe machine learning (ML) framework and Latent Dirichlet Allocation (LDA) topic modeling tool were used to collect and analyze behavioral data on EE. Data from a subcommunity of Reddit, /r/loseit, were analyzed. This dataset included all posts and feedback from July 2014 to May 2018, comprising 185,950 posts and 3,528,107 comments. In addition, deleted and improperly collected data were eliminated. Stochastic gradient descent-based ML classifier with an accuracy of 90.64% was developed to collect refined behavioral data of online users with EE behaviors. The expert group that labeled the dataset to train the ML classifiers included a medical doctor specializing in EE diagnosis and a nutritionist with profound knowledge of EE behavior. The experts labeled 5126 posts as EE (coded as 1) or others (coded as 0). Finally, the topic modeling process was conducted with LDA.ResultsThe following 4 macroperspective topics of online EE behaviors were identified through linguistic evidence regarding each topic: addressing feelings, sharing physical changes, sharing and asking for dietary information, and sharing dietary strategies. The 5 main topics of feedback were dietary information, compliments, consolation, automatic bot feedback, and health information. The feedback topic distribution significantly differed depending on the type of EE behavior (overall P<.001).ConclusionsThis study introduces a data-driven approach for analyzing behavior patterns of social website users with EE behaviors. We discovered the possibility of the LDA topic model as an exploratory user study method for abnormal behaviors in medical research. We also investigated the possibilities of ML- and topic modeling-based classifiers to automatically categorize text-based behavioral data, which could be applied to personalized medicine in future research.

Dataset Information

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

Publications

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

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