Alcoholism, clinical and experimental research最新文献

{"title":"Cost-effectiveness and cost-utility analyses of a web-based computer-tailored intervention for prevention of binge drinking among Spanish adolescents.","authors":"A. Vargas-Martínez, M. Lima-Serrano, M. Trapero-Bertran","doi":"10.21203/rs.3.rs-34394/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-34394/v1","url":null,"abstract":"BACKGROUND\u0000Binge drinking (BD) among adolescents is a public health concern worldwide. This study assessed the cost-effectiveness and cost-utility of a web-based computer-tailored intervention to prevent BD in adolescence.\u0000\u0000\u0000METHODS\u0000The sample was drawn from a study evaluating the Alerta Alcohol program. The population consisted of adolescents 15 to 19 years of age. Data were recorded at baseline (January to February 2016) and after 4 months (May to June 2017) and were used to estimate costs and health outcomes, as measured by the number of BD occasions and quality-adjusted life years (QALYs). Incremental cost-effectiveness and cost-utility ratios were calculated from National Health Service (NHS) and societal perspectives and for a time horizon of 4 months. A multivariate deterministic sensitivity analysis of best/worst scenarios by subgroups was used to account for uncertainty.\u0000\u0000\u0000RESULTS\u0000The cost of reducing BD occasions by one per month was €16.63 from the NHS perspective, which from the societal perspective resulted in savings of €7986.37. From the societal perspective, the intervention resulted in an incremental cost of €71.05 per QALY gained from the NHS perspective and this was dominant, resulting in savings of €34,126.64 per QALY gained in comparison with the control group. Subgroup analyses showed that the intervention was dominant for girls from both the perspectives and for individuals 17 years or older from the NHS perspective.\u0000\u0000\u0000CONCLUSIONS\u0000Computer-tailored feedback is a cost-effective way to reduce BD and increase QALYs among adolescents. However, long-term follow-up is needed to evaluate more fully changes in both BD and health-related quality of life.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2020-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87333351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can fetal alcohol exposure increase the risk of hypertension? A new study in children and adolescents diagnosed with fetal alcohol spectrum disorder suggests it can.","authors":"K. Moritz, N. Reid, L. Akison","doi":"10.1111/acer.14175","DOIUrl":"https://doi.org/10.1111/acer.14175","url":null,"abstract":"Prenatal alcohol exposure (PAE) is increasingly recognized as being associated with a wide range of physical health problems, in addition to the well-defined neurocognitive difficulties that have been reported (Mattson et al., 2019). In line with other prenatal perturbations, including smoking, inadequate nutrition and exposure to stress, exposure of the fetus to alcohol during critical stages of development may contribute to 'developmental origins of health and disease' (DOHaD), as first proposed by Barker and colleagues (1995). DOHaD suggests that a suboptimal environment in early development may increase susceptibility to conditions such as hypertension, insulin resistance and obesity, which are risk factors for prevalent non-communicable chronic diseases such as cardiovascular disease and type II diabetes (Hanson and Gluckman, 2011). This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88186281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar hypermetabolism in alcohol use disorder: compensatory mechanism or maladaptive plasticity?","authors":"L. Ritz, S. Segobin, C. Lannuzel, A. Laniepce, C. Boudehent, N. Cabé, F. Eustache, F. Vabret, H. Beaunieux, A. Pitel","doi":"10.1111/acer.14158","DOIUrl":"https://doi.org/10.1111/acer.14158","url":null,"abstract":"BACKGROUND\u0000Despite severe structural brain abnormalities within the fronto-cerebellar circuit (FCC), cerebellar metabolism studied with FDG-PET is relatively preserved in patients with alcohol use disorder (AUD). The compensatory role of the cerebellum has been explored mainly through fMRI examination of AUD patients with preserved level of performance. The present study aims at examining cerebellar metabolism and its relationship with regional brain metabolism and neuropsychological functioning in AUD patients.\u0000\u0000\u0000METHODS\u0000Thirty-two recently detoxified AUD patients and 23 controls underwent an FDG-PET examination at rest. Participants also performed a neuropsychological battery assessing executive functions, verbal memory and ataxia.\u0000\u0000\u0000RESULTS\u0000Compared to controls, AUD patients had higher glucose-uptake in the cerebellar lobules VIII, in association with hypometabolism notably in several nodes of the FCC. Cerebellar hypermetabolism correlated negatively with regional hypometabolism in the premotor and frontal cortices. This pattern of regional hypermetabolism and hypometabolism related to ataxia and working memory deficits.\u0000\u0000\u0000CONCLUSIONS\u0000These specific brain-behaviour relationships do not fulfil the criteria for brain compensatory processes. Cerebellar hypermetabolism may rather reflect the involvement of different pathological mechanisms, leading to a maladaptive plasticity phenomenon within the FCC in AUD patients who are early in abstinence. Further studies are required to examine the contributions of structural and functional connectivity alterations in the cerebellar hypermetabolism and the changes of these pathological mechanisms with abstinence or relapse. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79832635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome-wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption among European American Male Veterans.","authors":"Ke Xu, J. Montalvo-Ortiz, Xinyu Zhang, S. Southwick, J. Krystal, R. Pietrzak, J. Gelernter","doi":"10.1111/acer.14168","DOIUrl":"https://doi.org/10.1111/acer.14168","url":null,"abstract":"BACKGROUND\u0000Hazardous alcohol consumption has significant adverse medical consequences. These effects may be mediated, in part, by alterations in DNA methylation. Thus, DNA methylation signatures in peripheral cells may provide biomarkers of the medical impact of alcohol use and the risk for future alcohol consumption.\u0000\u0000\u0000METHOD\u0000Using a high density methylation array, we characterized epigenome-wide DNA methylation in saliva cells with respect to alcohol consumption in a large cohort of male European American veterans. In this study, DNA methylation of over 870,000 CpG DNA sites was profiled in 1,135 European American men. Alcohol consumption was assessed using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Linear regression was applied in an epigenome-wide association study (EWAS), adjusted for confounders. Gene set enrichment analysis was performed in the KEGG database with a correction for gene length.\u0000\u0000\u0000RESULTS\u0000We found that a total of 70 CpG sites reached EWAS-corrected significance (p<6E-08) with small effects on alcohol consumption for individual CpG sites, including 64 new CpG sites and six CpG sites that were previously reported as associated with alcohol use disorder, liver function, body mass index, and lipid metabolism. The most significant CpG site was located in SLC7A11(t=-11.34, p=2.66E-28), a gene involved specifically in cysteine and glutamate transportation. The 70 significant CpG sites were located on 44 genes, including genes involved in amino acid transport and metabolism systems. We identified 68 pathways with a false discovery rate <0.05.\u0000\u0000\u0000CONCLUSION\u0000We identified novel DNA methylation sites associated with alcohol consumption. Results may shed light on peripheral mechanisms of alcohol consumption on adverse health outcomes among heavy drinkers. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78358917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unpacking Genetic Risk Pathways for College Student Alcohol Consumption: The Mediating Role of Impulsivity.","authors":"Albert J Ksinan, Jinni Su, Fazil Aliev, Danielle M Dick","doi":"10.1111/acer.14157","DOIUrl":"10.1111/acer.14157","url":null,"abstract":"<p><strong>Background: </strong>The period of college represents a particularly risky developmental stage with regard to alcohol use, as college students engage in more risky drinking behaviors than their noncollege peers, and such problematic alcohol use is associated with far-reaching negative consequences. Existing findings from genome-wide association studies (GWAS) indicate that alcohol consumption has a complex polygenic etiology. Currently, there is a lack of studies examining genetic risk for alcohol consumption using polygenic risk scores (PRS) in college samples. In this study, we examined whether alcohol-specific and risky behavior-related PRS were longitudinally associated with alcohol consumption among college students and whether this effect might be partially mediated by impulsivity domains.</p><p><strong>Methods: </strong>The sample included n = 2,385 European ancestry (EA) and n = 1,153 African ancestry (AA) college students assessed over the course of 4 years. To indicate genetic risk, 2 PRS were created based on recent large-scale GWAS: alcohol consumption (Liu et al., 2019) -drinks per week (DPW)-PRS and risky behaviors (Linnér et al., 2019) -RISK-PRS. The main outcome was alcohol consumption, measured across 4 waves of follow-up data. The UPPS-P impulsivity subscales were examined as mediators of the genetic effect on alcohol consumption.</p><p><strong>Results: </strong>The results from structural equation modeling showed that among EA students, both DPW-PRS and RISK-PRS had significant positive effects on alcohol consumption above and beyond UPPS dimensions and control variables. RISK-PRS explained larger portion of variance in alcohol consumption than DPW-PRS. RISK-PRS showed a significant indirect effect on alcohol consumption through sensation seeking and lack of perseverance; no significant indirect effect of DPW-PRS was found. No significant association of either PRS or alcohol consumption was found for AA participants.</p><p><strong>Conclusions: </strong>The current results found that PRS related to more broadly defined risky behaviors predicted alcohol consumption across college years and that this association was partially mediated via dimensions of impulsivity.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83919253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOP receptor antagonists decrease alcohol drinking in the dark in C57BL/6J mice.","authors":"Gloria Brunori, Michelle Weger, Jennifer Schoch, Katarzyna M Targowska-Duda, Megan Barnes, A. M. Borruto, L. Rorick‐Kehn, N. Zaveri, J. Pintar, R. Ciccocioppo, L. Toll, A. Cippitelli","doi":"10.1111/acer.14165","DOIUrl":"https://doi.org/10.1111/acer.14165","url":null,"abstract":"BACKGROUND\u0000The nociceptin/orphanin FQ opioid peptide (NOP) receptor and its endogenous ligand N/OFQ have been implicated in the regulation of drug and alcohol use disorders. In particular, evidence demonstrated that NOP receptor activation blocks reinforcing and motivating effects of alcohol across a range of behavioral measures, including alcohol intake, conditioned place preference and vulnerability to relapse.\u0000\u0000\u0000METHODS\u0000Here, we show the effects of pharmacological activation and inhibition of NOP receptors on binge-like alcohol consumption, as measured by the \"drinking in the dark\" (DID) model in C57BL/6J mice.\u0000\u0000\u0000RESULTS\u0000We found that two potent and selective NOP agonists AT-202 (0, 0.3, 1, 3 mg/kg) and AT-312 (0, 0.3, 1 mg/kg) did not affect binge alcohol drinking at doses that do not affect locomotor activity. AT-202 also failed to alter DID behavior when administered to mice previously exposed to chronic alcohol treatment with an alcohol-containing liquid diet. Conversely, treatment with either the high affinity NOP receptor antagonist SB-612111 (0, 3, 10, 30 mg/kg) or the selective antagonist LY2817412 (0, 3, 10, 30 mg/kg) decreased binge drinking. SB-612111 was effective at all doses examined, LY2817412 was effective at 30 mg/kg. Consistently, NOP receptor knockout mice consumed less alcohol compared to wild type. SB-612111 reduced DID and increased sucrose consumption at doses that do not appear to affect locomotor activity. However, the high dose of SB-612111 (30 mg/kg) reduced alcohol intake but failed to inhibit preference in a two-bottle choice DID model that can assess moderate alcohol intake.\u0000\u0000\u0000CONCLUSIONS\u0000The present results suggest that NOP receptor inhibition rather than activation may represent a valuable approach for treatment of alcohol use disorders characterized by excessive alcohol consumption such as binge drinking. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74213689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Functional Magnetic Resonance Imaging to Test Pharmacotherapies for Alcohol Use Disorder: A Systematic Review.","authors":"Erica N Grodin, Lara A Ray","doi":"10.1111/acer.14167","DOIUrl":"10.1111/acer.14167","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) is a chronic relapsing condition that represents a significant public health concern. Pharmacological treatment development for AUD is a top research priority, and many studies are being conducted to evaluate potential AUD treatments. Understanding the brain circuitry impacted by addiction is crucial for the development of efficacious pharmacological interventions. These neuroadaptations can be probed noninvasively using functional magnetic resonance neuroimaging (fMRI). fMRI may be an effective tool to identify biomarkers for AUD pharmacotherapies, evaluating changes associated with pharmacological treatment. Thus, the present qualitative review of the literature focuses on the role of fMRI as a tool for medication development for AUD. The aim of this review was to assemble research across a range of fMRI paradigms to study the effectiveness of pharmacological treatments of adult AUD. First, we present a qualitative review of fMRI AUD pharmacotherapy studies, differentiating studies based on their dosing regimen. Second, we provide recommendations for the field to improve the use of fMRI as a biomarker for AUD pharmacotherapy.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88650693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study.","authors":"Jody Tanabe, Dorothy J Yamamoto, Brianne Sutton, Mark S Brown, Paula L Hoffman, Ellen L Burnham, Deborah H Glueck, Boris Tabakoff","doi":"10.1111/acer.14173","DOIUrl":"10.1111/acer.14173","url":null,"abstract":"<p><strong>Background: </strong>Acute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein-coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals.</p><p><strong>Methods: </strong>Twenty-four healthy participants were assigned by convenience to receive either 0.6 g/kg alcohol orally (n = 12) or acetate intravenously (n = 12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole-brain CBF maps were compared between placebo and drug using a paired t-test, and set at a threshold of p < 0.05 corrected for multiple comparisons (k ≥ 142 voxels, ≥3.78 cm³ ), voxel-level p < 0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS-7).</p><p><strong>Results: </strong>Compared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS-7 scores (p < 0.001).</p><p><strong>Conclusions: </strong>Increased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88217711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-month Follow up of the Families on Track Intervention Pilot Trial for Children with Fetal Alcohol Spectrum Disorders and Their Families.","authors":"C. Petrenko, Elizabeth M. Demeusy, Michelle E. Alto","doi":"10.1111/acer.14180","DOIUrl":"https://doi.org/10.1111/acer.14180","url":null,"abstract":"BACKGROUND\u0000When the primary disabilities associated with fetal alcohol spectrum disorders (FASD) are not well supported, individuals are at higher risk for mental health problems and other secondary conditions. The Families on Track intervention was designed to prevent secondary conditions and improve family functioning in children with FASD. Promising results from a pilot study demonstrated positive effects on child and caregiver outcomes immediately following the intervention. The objective of this study was to examine the sustainability of these effects 6-months post-intervention.\u0000\u0000\u0000METHODS\u0000Thirty children (ages 4 to 8) with prenatal alcohol exposure and their caregivers were enrolled in the original study. Families were randomized to the Families on Track intervention or an active comparison group that provided comprehensive assessment and individualized feedback. The intervention integrated a positive parenting curriculum and a child skills group. Families were assessed at baseline, post-intervention, and 6-month follow up visits. Follow up data were available for 24 families on child and caregiver outcomes. Data were analyzed using effect size calculations and analysis of variance techniques.\u0000\u0000\u0000RESULTS\u0000Relative to the comparison group, intervention families showed continued gains in parenting efficacy and maintained prior improvements in FASD knowledge over the follow-up period. Although intervention families reported a decrease in their needs being met over the follow up period, they continued to report their needs being met to greater extent than those in the comparison group. Consistent with post-intervention outcomes, children in both groups exhibited similar decreases in child disruptive behavior 6 months following the intervention. Unfortunately, positive gains seen at post-intervention for child self-esteem and emotion regulation were attenuated at follow-up.\u0000\u0000\u0000CONCLUSIONS\u0000This pilot study yielded promising effects on important areas of caregiver functioning. However, the intervention's impact on child functioning waned over time, suggesting the need for sustained or alternate child intervention.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82896307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal microbial products from alcohol-fed mice contribute to intestinal permeability and peripheral immune activation.","authors":"Derrick R. Samuelson, Min Gu, J. Shellito, P. Molina, Christopher M. Taylor, Meng Luo, D. Welsh","doi":"10.1111/acer.14176","DOIUrl":"https://doi.org/10.1111/acer.14176","url":null,"abstract":"BACKGROUND\u0000Alcohol use causes significant disruption of intestinal microbial communities, yet exactly how these dysbiotic communities interact with the host is unclear. We sought to understand the role of microbial products associated with alcohol-dysbiosis in mice on intestinal permeability and immune activation in an in-vitro model system.\u0000\u0000\u0000METHODS\u0000Microbiota samples from binge-on-chronic alcohol-fed and pair-fed male and female mice were cultured in Gifu Anaerobic Broth for 24 hours under anaerobic conditions. Live/whole organisms were removed, microbial products were collected, and added to human peripheral blood mononuclear cells (PBMC) or polarized C2BBe1 intestinal epithelial monolayers. Following stimulation, transepithelial electrical resistance (TEER) was measured using a volt/ohm meter and immune activation of PBMC was assessed via flow cytometry.\u0000\u0000\u0000RESULTS\u0000Microbial products from male and female alcohol-fed mice significantly decreased TEER (mean percentage change from baseline alcohol-fed 0.86 Ω/cm2 v. pair-fed 1.10 Ω/cm2 ) compared to microbial products from control mice. Following ex-vivo stimulation immune activation of PBMC was assessed via flow cytometry. We found that microbial products from alcohol-fed mice significantly increased the percentage of CD38+ CD4+ (mean alcohol-fed 17.32%+0.683% SD v. mean pair-fed 14.2%+1.21% SD, P<0.05) and CD8+ (mean alcohol-fed 20.28%+0.88% SD v. mean pair-fed 12.58%+3.59% SD, P<0.05) T-cells.\u0000\u0000\u0000CONCLUSIONS\u0000Collectively, these data suggest that microbial products contribute to immune activation and intestinal permeability associated with alcohol dysbiosis. Further, utilization of these ex-vivo microbial product assays will allow us to rapidly assess the impact of microbial products on intestinal permeability and immune activation and to identify probiotic therapies to ameliorate these defects. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79446880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}