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Westlake University Researchers Found Gut Microbiota Might Underlie the Predisposition of Healthy Individuals to COVID-19

Chi ZHANG
11, 2020

PRESS INQUIRIES Yi FENG
Email: fengyi@westlake.edu.cn
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During the COVID-19 global epidemic, it was noticed that individuals displayed different levels of severity after contracting COVID-19, but the cause of such disparity in susceptibility remained unknown. A joint research paper shedding light on the cause was published by Westlake University Principal Investigators (PIs) Ju-Sheng Zheng and Tiannan Guo and their teams in collaboration with Dr. Yu-ming Chen and his team at Sun Yat-Sen University on medRxiv on April 25th, 2020.


The researchers knew from other previous research that ACE2, an important enzyme regulating inflammation, is used by the coronavirus to infect the human body. They also knew that this enzyme is found in higher concentrations in parts of the intestines than in the lungs. Thus, ACE2 strongly influence the balance or combination of microorganisms and substances in the gut. More than 60% of patients are experiencing gastrointestinal symptoms such as diarrhea, nausea or vomiting. So, the PIs and their teams decided to look at gut microbiota, communities of microorganisms that live within the intestines and fulfill important functions.


Tiannan Guo’s lab had previously discovered important biomarkers (biological indicators) in the blood serum of severe COVID-19 patients. Through systematically monitoring proteins and metabolites (substances formed for or from metabolic processes such as digestion), they found unique molecular changes as well as specific biomarkers in the blood serum of severe cases.


In collaboration with Guo’s lab, Zheng’s lab joined the follow-up research by looking at healthy individuals. The researchers established a risk score based on statistical analysis of 20 major biomarkers in the blood serum of COVID-19 patients. This proteomic risk score (PRS) was found to be correlated with so-called inflammatory cytokines, which are signaling molecules that play a role in activating inflammatory immune responses such as heat, swelling, etc.


(Figure 1: Study design and analysis)



They verified the correlation between the score and the cytokines by analyzing proteomic big data of healthy individuals. They also discovered that certain features of the gut microbiota in healthy individuals offer high predictability of the occurrence of the 20 significant biomarkers. Furthermore, both, the score and the occurrence of cytokines, are strongly associated with certain features of gut microbiota. This implies that certain features of gut microbiota may be a significant indicator for higher predisposition of healthy individuals to COVID-19. The higher the score, the more likely it is for an individual to experience severe symptoms after infection.


(Figure 2: Correlations of certain features of severe COVID-19 with inflammatory factors among healthy individuals)


Thus, the researchers found that the predisposition of healthy individuals to the disease and a potential severe symptom development after infection with Covid-19 could be both predicted for healthy individuals with certain features of gut microbiota. Also, an analysis of the metabolites in the gut suggested the underlying mechanisms. Potential amino acid-related pathways seem to link gut microbiota to inflammation.


(Figure 3: Graph indicating pathways linking certain gut microbiota and inflammation)

 

The researchers hope that the results can help improve clinical diagnosis and enable more effective treatment plans. At Westlake University, researchers such as Zheng and Guo are continuously working around the clock to get a better understanding of the disease in hope to contribute to solving the global health crisis.