Aishwarya Thakurdesai, Suman K. Jha, Iyabo Erinkitola, Aula Said, Thwisha Joshi, Melanie L. Schwandt, Dipendra Parajuli, Ashwani K. Singal, Maiying Kong, Matthew C. Cave, Vatsalya Vatsalya
{"title":"酒精使用障碍和临床血清锌水平低患者的肠道-免疫-肝轴。","authors":"Aishwarya Thakurdesai, Suman K. Jha, Iyabo Erinkitola, Aula Said, Thwisha Joshi, Melanie L. Schwandt, Dipendra Parajuli, Ashwani K. Singal, Maiying Kong, Matthew C. Cave, Vatsalya Vatsalya","doi":"10.1111/acer.15408","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Thirty-nine male and female AUD patients were grouped by normal [≥71 <i>μ</i>g/dL (Group 1, number (<i>n</i>) = 26)] and low [<71 <i>μ</i>g/dL (Group 2, <i>n</i> = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Group 2 females exhibited lower LTDH than Group 2 males (<i>p</i> = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (<i>p</i> = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (<i>p</i> = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (<i>R</i><sup>2</sup> = 0.633, <i>p</i> = 0.037).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.</p>\n </section>\n </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels\",\"authors\":\"Aishwarya Thakurdesai, Suman K. Jha, Iyabo Erinkitola, Aula Said, Thwisha Joshi, Melanie L. Schwandt, Dipendra Parajuli, Ashwani K. Singal, Maiying Kong, Matthew C. Cave, Vatsalya Vatsalya\",\"doi\":\"10.1111/acer.15408\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Thirty-nine male and female AUD patients were grouped by normal [≥71 <i>μ</i>g/dL (Group 1, number (<i>n</i>) = 26)] and low [<71 <i>μ</i>g/dL (Group 2, <i>n</i> = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Group 2 females exhibited lower LTDH than Group 2 males (<i>p</i> = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (<i>p</i> = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (<i>p</i> = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (<i>R</i><sup>2</sup> = 0.633, <i>p</i> = 0.037).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.</p>\\n </section>\\n </div>\",\"PeriodicalId\":72145,\"journal\":{\"name\":\"Alcohol (Hanover, York County, Pa.)\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alcohol (Hanover, York County, Pa.)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/acer.15408\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"SUBSTANCE ABUSE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alcohol (Hanover, York County, Pa.)","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/acer.15408","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SUBSTANCE ABUSE","Score":null,"Total":0}
The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels
Background
Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients.
Methods
Thirty-nine male and female AUD patients were grouped by normal [≥71 μg/dL (Group 1, number (n) = 26)] and low [<71 μg/dL (Group 2, n = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers.
Results
Group 2 females exhibited lower LTDH than Group 2 males (p = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (p = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (p = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (R2 = 0.633, p = 0.037).
Conclusion
Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.
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