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Chronic alcohol consumption compromises gut barrier integrity and promotes endotoxemia:Implications for sepsis susceptibility in immunocompromised hosts 认领 引用
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作者 Thansita Bhunyakarnjanarat Chatsuree Suksamai +3 位作者 Dhammika Leshan Wannigama Kent Doi Wiwat Chancharoenthana Asada Leelahavanichkul 《Animal Models and Experimental Medicine》 CAS CSCD 2026年第5期967-979,共13页
Background:Gut barrier integrity prevents microbial translocation and systemic infection.Chronic alcohol disrupts this barrier,but its role in infection susceptibility among immune-compromised hosts remains unclear.We... Background:Gut barrier integrity prevents microbial translocation and systemic infection.Chronic alcohol disrupts this barrier,but its role in infection susceptibility among immune-compromised hosts remains unclear.We investigated how chronic alcohol promotes gut barrier dysfunction,endotoxemia,and dysbiosis,predisposing to bacterial translocation and sepsis.Methods:Twenty-four-week-old female FcγRIIb−/−and wild-type mice received oral gavage of 35%ethanol(4.2 g/kg/day)or water for 10 weeks.Gut barrier integrity was assessed by serum endotoxin,FITC-dextran permeability,ileal claudin-1,and in-testinal IgGeutrophil infiltration.Systemic inflammation was evaluated by serum TNF-α,IL-1β,and IL-6;gut microbiota by 16S rRNA sequencing.Bone marrow-derived macrophages and hepatocytes from both genotypes were stimulated with LPS or ethanol to assess inflammatory responses,mitochondrial damage,and cGAS-STING activation.Results:Chronic alcohol induced gut barrier dysfunction in both groups,with more severe effects in FcγRIIb−/−mice,which showed marked increases in serum endotoxin and FITC-dextran permeability,reduced claudin-1,and enhanced intestinal IgG depo-sition with neutrophil accumulation.Serum TNF-α,IL-1β,and IL-6 were significantly elevated,reflecting a sepsis-like profile.Alcohol induced dysbiosis with an increased Firmicutes-to-Bacteroidota ratio,elevated Lachnospiraceae,and reduced Alistipes,Bacteroides,and Odoribacter.In vitro,LPS elicited stronger inflammation than ethanol in both cell types,with FcγRIIb−/−cells producing greater cytokine levels.Both stimuli caused comparable mitochondrial damage and cGAS-STING activation.Conclusions:Alcohol-induced gut barrier dysfunction,endotoxemia,and dysbiosis predispose to bacterial translocation and early sepsis,particularly in hosts with impaired inhibitory Fcγreceptor signaling,supporting gut barrier preservation as a strategy for preventing alcohol-associated infections and sepsis. 展开更多
关键词 alcohol endotoxemia gut barrier dysfunction gut microbiota sepsis susceptibility
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Modeling vaccination strategies with limited early COVID-19 vaccine access in low-and middle-income countries:A case study of Thailand 认领 引用 被引量：2
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作者 Suparinthon Anupong Tanakorn Chantanasaro +8 位作者 Chaiwat Wilasang Natcha CJitsuk Chayanin Sararat Kan Sornbundit Busara Pattanasiri Dhammika Leshan Wannigama Mohan Amarasiri Sudarat Chadsuthi Charin Modchang 《Infectious Disease Modelling》 CSCD 2023年第4期1177-1189,共13页
Low-and middle-income countries faced significant challenges in accessing COVID-19 vaccines during the early stages of the pandemic.In this study,we utilized an agestructured modeling approach to examine the implicati... Low-and middle-income countries faced significant challenges in accessing COVID-19 vaccines during the early stages of the pandemic.In this study,we utilized an agestructured modeling approach to examine the implications of various vaccination strategies,vaccine prioritization,and vaccine rollout speeds in Thailand,an upper-middleincome country experiencing vaccine shortages during the early stages of the pandemic.The model directly compares the effectiveness of several vaccination strategies,including the heterologous vaccination where CoronaVac(CV)vaccine was administered as the first dose,followed by ChAdOx1 nCoV-19(AZ)vaccine as the second dose,under varying disease transmission dynamics.We found that the traditional AZ homologous vaccination was more effective than the CV homologous vaccination,regardless of disease transmission dynamics.However,combining CV and AZ vaccines via either parallel homologous or heterologous vaccinations was more effective than relying solely on AZ homologous vaccination.Additionally,prioritizing vaccination for the elderly aged 60 years and above was the most effective way to reduce mortality when community transmission is wellcontrolled.On the other hand,prioritizing workers aged 20e59 was most effective in lowering COVID-19 cases,irrespective of the transmission dynamics.Lastly,despite the vaccine prioritization strategy,rapid vaccine rollout speeds were crucial in reducing COVID-19 infections and deaths.These findings suggested that in low-and middle-income countries where early access to high-efficacy vaccines might be limited,obtaining any accessible vaccines as early as possible and using them in parallel with other higherefficacy vaccines might be a better strategy than waiting for and relying solely on higher-efficacy vaccines. 展开更多
关键词 COVID-19 Low-and middle-income countries Vaccine inequality Thailand
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