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1.
Int J Mol Sci ; 22(21)2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1480797

ABSTRACT

The intestinal barrier plays an extremely important role in maintaining the immune homeostasis of the gut and the entire body. It is made up of an intricate system of cells, mucus and intestinal microbiota. A complex system of proteins allows the selective permeability of elements that are safe and necessary for the proper nutrition of the body. Disturbances in the tightness of this barrier result in the penetration of toxins and other harmful antigens into the system. Such events lead to various digestive tract dysfunctions, systemic infections, food intolerances and autoimmune diseases. Pathogenic and probiotic bacteria, and the compounds they secrete, undoubtedly affect the properties of the intestinal barrier. The discovery of zonulin, a protein with tight junction regulatory activity in the epithelia, sheds new light on the understanding of the role of the gut barrier in promoting health, as well as the formation of diseases. Coincidentally, there is an increasing number of reports on treatment methods that target gut microbiota, which suggests that the prevention of gut-barrier defects may be a viable approach for improving the condition of COVID-19 patients. Various bacteria-intestinal barrier interactions are the subject of this review, aiming to show the current state of knowledge on this topic and its potential therapeutic applications.


Subject(s)
Bacterial Infections/therapy , Haptoglobins/metabolism , Intestinal Mucosa/metabolism , Probiotics/therapeutic use , Protein Precursors/metabolism , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/pathology , Bacterial Physiological Phenomena , Gastrointestinal Microbiome , Humans , Intestinal Mucosa/microbiology , Mucus/metabolism , Tight Junctions/metabolism
2.
Front Immunol ; 12: 686240, 2021.
Article in English | MEDLINE | ID: covidwho-1285294

ABSTRACT

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.


Subject(s)
COVID-19/immunology , Gastrointestinal Microbiome/immunology , Inflammation/immunology , Intestines/physiology , SARS-CoV-2/physiology , Female , Glycomics , Haptoglobins/metabolism , Humans , Lipidomics , Male , Metabolomics , Middle Aged , Permeability , Protein Precursors/metabolism , Tight Junctions/metabolism
3.
Clin Transl Gastroenterol ; 12(6): e00348, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1259760

ABSTRACT

INTRODUCTION: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications. METHODS: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered. RESULTS: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events. DISCUSSION: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.


Subject(s)
COVID-19 , Endotoxemia , Haptoglobins/metabolism , Intestinal Mucosa , Protein Precursors/metabolism , SARS-CoV-2 , Thrombosis , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , Correlation of Data , Endotoxemia/diagnosis , Endotoxemia/metabolism , Endotoxemia/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/virology , Lipopolysaccharides/analysis , Male , Middle Aged , Permeability , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology
4.
Front Immunol ; 12: 665300, 2021.
Article in English | MEDLINE | ID: covidwho-1226978

ABSTRACT

The irruption of SARS-CoV-2 during 2020 has been of pandemic proportions due to its rapid spread and virulence. COVID-19 patients experience respiratory, digestive and neurological symptoms. Distinctive symptom as anosmia, suggests a potential neurotropism of this virus. Amongst the several pathways of entry to the nervous system, we propose an alternative pathway from the infection of the gut, involving Toll-like receptor 4 (TLR4), zonulin, protease-activated receptor 2 (PAR2) and zonulin brain receptor. Possible use of zonulin antagonists could be investigated to attenuate neurological manifestations caused by SARS-CoV-19 infection.


Subject(s)
COVID-19/complications , Haptoglobins/metabolism , Nervous System Diseases/complications , Protein Precursors/metabolism , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/virology , Brain/metabolism , Brain/virology , COVID-19/metabolism , COVID-19/virology , Complement System Proteins/metabolism , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/metabolism , Gastrointestinal Diseases/virology , Humans , Nervous System Diseases/metabolism , Nervous System Diseases/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Toll-Like Receptor 4/metabolism
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