A Systems Biology Approach to Study Systemic Inflammation

Severe COVID-19 Is Fueled by Disrupted Gut Barrier Integrity

10.1101/2020.11.13.20231209 ◽

2020 ◽

Author(s):

Leila B. Giron ◽

Harsh Dweep ◽

Xiangfan Yin ◽

Han Wang ◽

Mohammad Damra ◽

...

Keyword(s):

Systems Biology ◽

Lung Injury ◽

Gut Microbiota ◽

Systemic Inflammation ◽

Clinical Implications ◽

Metabolic Function ◽

Gut Barrier ◽

Barrier Integrity ◽

Tight Junction Permeability ◽

Injury Causes

ABSTRACTA disruption of the crosstalk between gut microbiota and the lung (gut-lung axis) 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. To test the possibility that a disrupted gut contributes to Coronavirus disease 2019 (COVID-19) severity, we used a systems biology approach to analyze plasma from COVID-19 patients with varying disease severity and controls. Severe COVID-19 is associated with a dramatic increase in tight junction permeability and translocation of bacterial and fungal products into blood. This intestinal disruption and microbial translocation correlate strongly with increased systemic inflammation and complement activation, lower gut metabolic function, and higher mortality. Our study highlights a previously unappreciated factor with significant clinical implications, disruption in gut barrier integrity, as a force that contributes to COVID-19 severity.

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Understanding mechanisms and seeking cures for Alzheimer's disease: why we must be “extraordinarily diverse”

AJP Cell Physiology ◽

10.1152/ajpcell.00111.2017 ◽

2017 ◽

Vol 313 (4) ◽

pp. C353-C361 ◽

Cited By ~ 4

Author(s):

Madhav Thambisetty

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Human Physiology ◽

Systems Biology ◽

Clinical Features ◽

Systemic Inflammation ◽

Molecular Mechanisms ◽

Population Level ◽

Alois Alzheimer ◽

Disease Modifying

After more than a century since Dr. Alois Alzheimer first described the pathological hallmarks accompanying the defining clinical features of the disease, we have yet to deliver any meaningful disease-modifying treatments to our patients. In this article, I present a rationale for the need to be “extraordinarily diverse” in seeking effective ways to treat or prevent this devastating disease. This approach is based on applying a systems-biology perspective at the population level, using a diverse array of “OMICS” methodologies to identify molecular mechanisms associated with well-established AD risk factors including systemic inflammation, obesity, and insulin resistance. We believe that applying this strategy to understand longitudinal changes in human physiology during aging is of paramount importance in identifying meaningful opportunities to intervene effectively in AD.

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A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining

BMC Medical Genomics ◽

10.1186/1755-8794-1-46 ◽

2008 ◽

Vol 1 (1) ◽

Cited By ~ 31

Author(s):

Bor-Sen Chen ◽

Shih-Kuang Yang ◽

Chung-Yu Lan ◽

Yung-Jen Chuang

Keyword(s):

Systems Biology ◽

Gene Regulatory Network ◽

Systemic Inflammation ◽

Regulatory Network ◽

Gene Regulatory

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Combining integrated systems-biology approaches with intervention-based experimental design provides a higher-resolution path forward for microbiome research

Behavioral and Brain Sciences ◽

10.1017/s0140525x18002911 ◽

2019 ◽

Vol 42 ◽

Author(s):

J. Alfredo Blakeley-Ruiz ◽

Carlee S. McClintock ◽

Ralph Lydic ◽

Helen A. Baghdoyan ◽

James J. Choo ◽

...

Keyword(s):

Systems Biology ◽

High Resolution ◽

Experimental Design ◽

Integrated Systems ◽

Microbiome Research ◽

Constructive Criticism

Abstract The Hooks et al. review of microbiota-gut-brain (MGB) literature provides a constructive criticism of the general approaches encompassing MGB research. This commentary extends their review by: (a) highlighting capabilities of advanced systems-biology “-omics” techniques for microbiome research and (b) recommending that combining these high-resolution techniques with intervention-based experimental design may be the path forward for future MGB research.

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