Leaky Gut Syndrome Is Associated with Endotoxemia and Serum (1→3)-β-D-Glucan in Severe Dengue Infection.

Wiwat Chancharoenthana,Polrat Wilairatana,Pornsawan Leaungwutiwong,Asada Leelahavanichkul,Weerapong Phumratanaprapin,Somratai Vadcharavivad,Wassawon Ariyanon,Supitcha Kamolratanakul,Suphasit Phatcharophaswattanakul

doi:10.3390/microorganisms9112390

Abstract

The hallmark of severe dengue infection is the increased vascular permeability and hemodynamic alteration that might be associated with an intestinal permeability defect. However, the mechanisms underlying the gastrointestinal-related symptoms of dengue are not well characterized. A prospective observational study was conducted on patients with dengue who were categorized according to: (i) febrile versus critical phase and (ii) hospitalized patients with versus without the warning signs to evaluate the gut barrier using lactulose-to-mannitol excretion ratio (LEMR). Serum endotoxins, (1→3)-β-D-glucan (BG), and inflammatory parameters were measured. A total of 48 and 38 patients were enrolled in febrile illness and critical phase, respectively, while 22 and 64 patients presented with or without the warning signs, respectively. At enrollment, a positive LEMR test was found in 20 patients (91%) with warning signs, regardless of phase of infection. Likewise, serum endotoxins and BG, the indirect biomarkers for leaky gut, prominently increased in patients who developed severe dengue when compared with the non-severe dengue (endotoxins, 399.1 versus 143.4 pg/mL (p < 0.0001); BG, 123 versus 73.8 pg/mL (p = 0.016)). Modest impaired intestinal permeability occurred in dengue patients, particularly those with warning signs, and were associated with endotoxemia and elevated BG. Thus, leaky gut syndrome might be associated with severity of dengue infection.

Highlights

This article is an open access articleDengue virus (DENV), the most prevalent mosquito-borne viral pathogen among humans globally, was identified by the World Health Organization (WHO) as one of the top 10 threats to global health in 2019 [1]
Serum (1→3)-β-D-glucan (BG) and lipopolysaccharides (LPS) have been proposed as indirect biomarkers of gut barrier defects in several publications [12,13,22–24], the association between these biomarkers and a standard gut permeability test in patients was clearly observed for the first time
LPS and gut barrier defects than serum Because (1→3)-β-D-glucan (BG), both LPS and BG were correlated with gut permeability injury, which may be useful for the prediction of severe dengue infection

Summary

Introduction

This article is an open access articleDengue virus (DENV), the most prevalent mosquito-borne viral pathogen among humans globally, was identified by the World Health Organization (WHO) as one of the top 10 threats to global health in 2019 [1]. An estimated annual incidence of dengue viral infection has increased progressively over the last 50 years [2]; approximately 40% of the world is at risk of dengue fever, and there are approximately 390 million infections a distributed under the terms and conditions of the Creative Commons. 60% of the global population by the year 2080 [3] This data set is more accurate than that analyzed in a previous study because dengue infection was used as the definition, not dengue fever, which may include atypical presentation in some individuals. The prediction of severe dengue during the febrile phase and appropriately prompt interventions are key to virus management and to reducing the mortality rate, which will decrease the societal healthcare burden of dengue

Methods

Results

Conclusion