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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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Microparticles at the crossroads of the gut-kidney axis:Mechanistic drivers and therapeutic horizons in hemodialysis 认领 引用
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作者 Thansita Bhunyakarnjanarat Asada Leelahavanichkul Wiwat Chancharoenthana 《World Journal of Nephrology》 2026年第2期140-153,共14页
Chronic kidney disease(CKD)and end-stage kidney disease(ESKD)pose significant global health challenges,with hemodialysis serving as a vital treatment for ESKD patients.Despite its life-sustaining role,hemodialysis is ... Chronic kidney disease(CKD)and end-stage kidney disease(ESKD)pose significant global health challenges,with hemodialysis serving as a vital treatment for ESKD patients.Despite its life-sustaining role,hemodialysis is associated with elevated cardiovascular morbidity and mortality,driven in part by the accumulation of uremic toxins.Recent research underscores the gut-kidney axis as a pivotal contributor to CKD progression and its complications,with gut microbiota dysbiosis amplifying uremic toxin production.Microparticles(MPs)-small extracellular vesicles released from cells-have emerged as key mediators in intercellular communication,inflammation,and vascular dysfunction.This review examines the role of MPs in the gut-kidney axis,with a focus on their contribution to uremic toxicity and clinical outcomes in hemodialysis patients.We explore how MPs,originating from endothelial cells,platelets,and gut microbiota,transport bioactive molecules,intensify inflammation,and impair endothelial function,thereby heightening cardiovascular risk.Furthermore,we assess their potential as biomarkers of disease severity and as novel therapeutic targets.By integrating current evidence,this review elucidates the intricate interplay between MPs,the gut-kidney axis,and uremic toxicity,offering fresh insights into improving outcomes for hemodialysis patients. 展开更多
关键词 Microparticles Gut-kidney axis Hemodialysis Uremic toxins Chronic kidney disease
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Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand? 认领 引用 被引量：21
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作者 Wiwat Chancharoenthana Asada Leelahavanichkul 《World Journal of Gastroenterology》 SCIE CAS 2019年第28期3684-3703,共20页
Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI ... Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established. 展开更多
关键词 Acute kidney injury Acute-on-chronic liver failure Chronic liver disease Hepatorenal syndrome Plasma perfusion and bilirubin adsorption and double plasma molecular absorption system Fractionated plasma separation and adsorption Molecular adsorbent recycling system Single-pass albumin dialysis
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Gastrointestinal manifestations of long-term effects after COVID-19 infection in patients with dialysis or kidney transplantation:An observational cohort study 认领 引用
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作者 Wiwat Chancharoenthana Supitcha Kamolratanakul +6 位作者 Asada Leelahavanichkul Wassawon Ariyanon Sutatip Chinpraditsuk Rattanaporn Saelim Somratai Vadcharavivad Weerapong Phumratanaprapin PolratWilairatana 《World Journal of Gastroenterology》 SCIE CAS 2023年第19期3013-3026,共14页
BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially ga... BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially gastrointestinal(GI)problems,during immunosuppressive therapy.AIM To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.METHODS This observational,prospective study included patients with COVID-19 infection,confirmed by reverse transcription polymerase chain reaction,with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset,either through the out-patient follow-up or by telephone interviews.RESULTS The 645 eligible participants consisted of 588 cases with hemodialysis(HD),38 patients with peritoneal dialysis(PD),and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these,577(89.5%) cases agreed to the interviews,while 64(10.9%)patients with HD and 4(10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups,respectively,and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524(56%) and 21/34(62%) in HD and PD,respectively,and 7/19(37%) KT recipients. Fatigue was the most prevalent(96%) of the non-GI tract symptoms,whereas anorexia(90.9%),loss of taste(64.4%),and abdominal pain(62.5%) were the first three common GI manifestations of Long-COVID. Notably,there were 6 cases of mesenteric panniculitis from 19patients with GI symptoms in the KT group.CONCLUSION Different from patients with non-chronic kidney disease,there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary. 展开更多
关键词 COVID-19 Kidney transplant Post-acute COVID-19 syndrome Long-COVID-19 Gastrointestinal SARS-CoV-2
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