Alcohol Use and Gastrointestinal Diseases.
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ABSTRACT:
SUBMITTER: Seitz HK
PROVIDER: S-EPMC7383275 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWhether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases.MethodsGenetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption.ResultsGenetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation.ConclusionsThis study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases.FundingThe Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.
| S-EPMC10017103 | biostudies-literature
Project description:Introduction: Alcohol is a carcinogen for human cancer. This contribution summarizes the relationships between alcohol use and gastrointestinal cancers, and implications for prevention. Methods: Comparative risk assessment and narrative literature review. Results: The following gastrointestinal cancer sites were found to be causally impacted by alcohol use: lip and oral cavity, pharynx other than nasopharynx, esophagus, colon and rectum, and liver. Globally, 368,000 deaths (304,000 men and 64,000 women) and more than 10 million disability-adjusted life years (DALYs) lost (10.1 million; 8.4 million men and 1.6 million women) in 2016 were attributable to alcohol use, making up about 10% of all deaths and DALYs lost due to these cancers, respectively. There are effective and cost-effective alcohol control policies available to reduce this burden, namely the best buys of increasing taxation, reducing availability, and banning advertisement. In addition, public knowledge about the alcohol-cancer link should be increased. Discussion: There are a number of assumptions underlying these estimates, but overall all of them seem to be conservative.
| S-EPMC7109294 | biostudies-literature
Project description:Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.
| S-EPMC10572150 | biostudies-literature
Project description:Gastrointestinal tract microbiota plays a key role in the regulation of the pathogenesis of several gastrointestinal diseases. In particular, the viral fraction, composed essentially of bacteriophages, influences homeostasis by exerting a selective pressure on the bacterial communities living in the tract. Gastrointestinal inflammatory diseases are mainly induced by bacteria, and have risen due to the emergence of antibiotic resistant strains. In the lack of effective treatments, phage therapy has been proposed as a clinical alternative to restore intestinal eubiosis, thanks to its immunomodulatory and bactericidal effect against bacterial pathogens, such as Clostridioides difficile in ulcerative colitis and invasive adherent Escherichia coli in Crohn's disease. In addition, genetically modified temperate phages could be used to suppress the transcription of bacterial virulence factors. In this review, we will highlight the latest advances in research in the field, as well as the clinical trials based on phage therapy in the area of gastroenterology.
| S-EPMC7565598 | biostudies-literature
Project description:Despite the great advances of life course epidemiology studies during the last decade in understanding the general health effects of employment trajectories, research has yet to evaluate the effects of employment trajectories along with other major risk factors, such as tobacco and alcohol consumption, on cardiovascular diseases (CVDs)-the main cause of deaths worldwide. This is highly relevant, since health advantages in one domain (e.g., being a permanent formal full-time worker) may offset health disadvantages in other domains (e.g., being a regular smoker or alcohol consumer); conversely, disadvantages in both domains may interact, leading to even greater health risks. Considering these knowledge gaps, this research has two main objectives: (1) to reconstruct simultaneous employment, tobacco use, and alcohol consumption trajectories over the life course (from birth to old age) and (2) to measure the association between these trajectories and CVD in old age. Drawing on a rich and comprehensive life history dataset and using multichannel sequence and regression analyses, we analyzed a cohort of individuals aged 65-75 in Chile, a Latin American country with high social inequalities and scarce research on this matter. Our study shows that following a trajectory of formal employment together with no tobacco and alcohol use reduces CVD risk by 36 percentage points relative to a similar employment trajectory but with regular tobacco and alcohol use. Even with an employment trajectory characterized by constant informal employment or permanent inactivity, a life course free of regular tobacco and alcohol use shows protective effects against CVD. This study stresses the importance of health policies that consider CVD as a condition that strongly depends on individual experiences in multiple life domains and across different life stages.
| S-EPMC7848642 | biostudies-literature
Project description:IntroductionThe causal effects of smoking and alcohol use on the risk of infectious diseases are unclear, and it is hard investigate them in an observational study due to the potential confounding factors. The aim of this study was to use Mendelian randomization (MR) techniques to assess the causalities between smoking, alcohol use and risk of infectious diseases.MethodsUnivariable and multivariable MR analyses were performed using genome-wide association data for the age of initiation of regular smoking (AgeSmk, N = 341,427), smoking initiation (SmkInit, N = 1,232,091), cigarettes per day (CigDay, N = 337,334), lifetime smoking (LifSmk, N = 462,690), drinks per week (DrnkWk, N = 941,280), sepsis (N = 486,484), pneumonia (N = 486,484), upper respiratory tract infection (URTI, N = 486,484) and urinary tract infection (UTI, N = 486,214) among individuals of European ancestry. Independent genetic variants that were significantly (P < 5 × 10-8) associated with each exposure were considered as instruments. The inverse-variance-weighted method was used in the primary analysis, which was followed by a series of sensitivity analyses.ResultsGenetically predicted SmkInit was associated with an increased risk of sepsis (OR 1.353, 95% CI 1.079-1.696, P = 0.009), pneumonia (OR 1.770, 95% CI 1.464-2.141, P = 3.8 × 10-9) and UTI (OR 1.445, 95% CI 1.184-1.764, P = 3 × 10-4). Moreover, genetically predicted CigDay was associated with a higher risk of sepsis (OR 1.403, 95% CI 1.037-1.898, P = 0.028) and pneumonia (OR 1.501, 95% CI 1.167-1.930, P = 0.00156). Furthermore, genetically predicted LifSmk was associated with an increased risk of sepsis (OR 2.200, 95% CI 1.583-3.057, P = 2.63 × 10-6), pneumonia (OR 3.462, 95% CI 2.798-4.285, P = 3.28 × 10-30), URTI (OR 2.523, 95% CI 1.315-4.841, P = 0.005) and UTI (OR 2.036, 95% CI 1.585-2.616, P = 3.0 × 10-8). However, there was no significant causal evidence for genetically predicted DrnkWk in sepsis, pneumonia, URTI or UTI. Multivariable MR analyses and sensitivity analyses showed that the above results for causal association estimations were robust.ConclusionIn this MR study, we demonstrated the causal association between tobacco smoking and risk of infectious diseases. However, no evidence was found to support causality between alcohol use and the risk of infectious diseases.
| S-EPMC10017901 | biostudies-literature
Project description:The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.
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Project description: Not available
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Project description:Mitochondria play a central role in the pathophysiology of inflammatory bowel disease (IBD) and colorectal cancer (CRC). The maintenance of mitochondrial function is necessary for a stable immune system. Mitochondrial dysfunction in the gastrointestinal system leads to the excessive activation of multiple inflammatory signaling pathways, leading to IBD and increased severity of CRC. In this review, we focus on the mitochondria and inflammatory signaling pathways and its related gastrointestinal diseases.
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Project description:The scientific basis and the clinical application of mAb therapies that target specific immunologic pathways for eosinophilic gastrointestinal diseases are areas of active interest. There is a growing recognition of a subset of patients with eosinophilic esophagitis whose disease does not respond well to topical steroids or elimination diets. In addition, long-term use of corticosteroids presents possible risks that are currently being evaluated. Systemic therapy with a biologic agent offers potential advantages as a global approach that could limit the need for multiple, locally active medical therapies and allergen avoidance. The identification of novel biologic strategies is ongoing, and the recent validation of instruments and outcome measures to assess disease activity has proved essential in demonstrating efficacy. Studies using biologics that target IL-13 pathways in the treatment of eosinophilic esophagitis have demonstrated substantial promise.
| S-EPMC6035775 | biostudies-literature