Immunoregulation of Ghrelin in neurocognitive sequelae associated with COVID-19: an in silico investigation

Russo, Cristina; Morello, Giovanna; Mannino, Giuliana; Russo, Antonella; Malaguarnera, Mariano

doi:10.1016/j.gene.2022.146647

Cited by 5 publications

(3 citation statements)

References 74 publications

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“…Notably, Ruminiclostridium 6 was previously found to have a strong positive correlation with the levels of ghrelin (32), which exerts immunomodulatory functions in COVID-19 infection, such as the suppressive effects on pro-in ammatory cytokine production including IL-1 β, IL-6 and TNF-α (33).…”

Section: Discussionmentioning

confidence: 98%

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Yan

Zhao

Huang

et al. 2023

Preprint

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Background COVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. Methods Based on two-sample Mendelian randomization framework, the causal effects of 131 microbiota in genus or species level and 452 plasma metabolites on severe COVID-19 are estimated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal bacteria in gut and the concentration of metabolites in plasma have been utilized as the instrument variables to infer whether they are causal factors of severe COVID-19. In addition, mediation analysis is conducted to find the potential link between the microbiota and metabolite which identified by polygenic Mendelian randomization analysis, while colocalization analysis has been performed to validate the causal relationships which identified by cis-Mendelian randomization analysis. Results Mendelian randomization support 13 microbiota and 53 metabolites, which are significantly causal association with severe COVID-19. Mediation analysis find 11 mediated relations, such as myo-inositol, 2-stearoylglycerophosphocholine and alpha-glutamyltyrosine, which appeared to mediate the association of Howardella and Ruminiclostridium 6 with severe COVID-19 respectively, while Butyrivibrio and Ruminococcus gnavus appeared to mediate the association of myo-inositol and N-acetylalanine respectively. Ruminococcus torques abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95). Conclusions Our study results highlight the causal relationships of gut microbiome and plasma metabolome for severe COVID-19, which have the promise to be served as clinical biomarkers for risk stratification and prognostication, and novel basis to unravel the pathophysiological mechanisms of severe COVID-19.

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Section: Discussionmentioning

confidence: 98%

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Yan

Zhao

Huang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Notedly, Ruminiclostridium 6 was previously found to have a strong positive correlation with the levels of ghrelin ( 33 ), which exerts immunomodulatory functions in COVID-19 infection, such as the suppressive effects on pro-inflammatory cytokine production including IL-1 β, IL-6 and TNF- α ( 34 ). Therefore, it is conceivable that the causal effect of Ruminiclostridium 6 on severe COVID-19 may result from ghrelin.…”

Section: Discussionmentioning

confidence: 99%

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Yan,

Zhao,

Huang

et al. 2023

Front. Immunol.

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BackgroundCOVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. However, the causal relationship between specific intestinal bacteria, metabolites and severe COVID-19 remains not clear.MethodsBased on two-sample Mendelian randomization (MR) framework, the causal effects of 131 intestinal taxa and 452 plasma metabolites on severe COVID-19 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal taxa and the concentration of plasma metabolites had been utilized as the instrument variables to infer whether they were causal factors of severe COVID-19. In addition, mediation analysis was conducted to find the potential association between the taxon and metabolite, and further colocalization analysis had been performed to validate the causal relationships.ResultsMR analysis identified 13 taxa and 53 metabolites, which were significantly associated with severe COVID-19 as causal factors. Mediation analysis revealed 11 mediated relationships. Myo-inositol, 2-stearoylglycerophosphocholine, and alpha-glutamyltyrosine, potentially contributed to the association of Howardella and Ruminiclostridium 6 with severe COVID-19, respectively. Butyrivibrio and Ruminococcus gnavus could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, Ruminococcus torques abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95).ConclusionsOur study highlights the potential causal relationships between gut microbiome, plasma metabolome and severe COVID-19, which potentially serve as clinical biomarkers for risk stratification and prognostication and benefit the mechanism mechanistic investigation of severe COVID-19.

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“…The CYP11A1-derived hydroxyderivatives are non-calcaemic or low calcaemic and can be used at high concentrations for therapeutic scopes: they can modulate gene expression by binding the receptor (VDR). Moreover, a bioinformatics approach reported that VDR could be used by other anti-inflammatory mediators, such as ghrelin, exerting an immunomodulatory function in the course of SARS-CoV-2 infection [20].…”

Section: Introductionmentioning

confidence: 99%

COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics

et al. 2023

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An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age. Therefore, the aim of this study was to evaluate the role of single nucleotide polymorphisms in these pathways, clarifying their impact in affecting COVID-19-related clinical features. Genetic polymorphisms were evaluated through real-time PCR. We prospectively enrolled 160 individuals: 139 patients were positive for SARS-CoV-2 detection. We detected different genetic variants able to affect the symptoms and oxygenation. Furthermore, two sub-analyses were performed considering gender and age, showing a different impact of polymorphisms according to these characteristics. This is the first study highlighting a possible contribution of genetic variants of these pathways in affecting COVID-19 clinical features. This may be relevant in order to clarify the COVID-19 etiopathogenesis and to understand the possible genetic contribution for further SARS infections.

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Immunoregulation of Ghrelin in neurocognitive sequelae associated with COVID-19: an in silico investigation

Cited by 5 publications

References 74 publications

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics

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