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The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

ABSTRACT: COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

SUBMITTER: Caterino M

PROVIDER: S-EPMC8431319 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

Caterino Marianna M Costanzo Michele M Fedele Roberta R Cevenini Armando A Gelzo Monica M Di Minno Alessandro A Andolfo Immacolata I Capasso Mario M Russo Roberta R Annunziata Anna A Calabrese Cecilia C Fiorentino Giuseppe G D'Abbraccio Maurizio M Dell'Isola Chiara C Fusco Francesco Maria FM Parrella Roberto R Fabbrocini Gabriella G Gentile Ivan I Castaldo Giuseppe G Ruoppolo Margherita M

International journal of molecular sciences 20210902 17

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohor ...[more]

PMID: 34502454

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Project description:BackgroundMetabolic homeostasis is substantially disrupted in critical illness. Given the pleiotropic effects of vitamin D, we hypothesized that metabolic profiles differ between critically ill patients relative to their vitamin D status.MethodsWe performed a metabolomics study on biorepository samples collected from a single academic medical center on 65 adults with systemic inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to vitamin D status in critical illness, we first generated metabolomic data using gas and liquid chromatography mass spectroscopy. We followed this by partial least squares-discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis to identify groups of metabolites and pathways that were differentiates of vitamin D status. Finally we performed logistic regression to construct a network model of chemical-protein target interactions important in vitamin D status.ResultsMetabolomic profiles significantly differed in critically ill patients with 25(OH)D ≤ 15 ng/ml relative to those with levels >15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl-glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH)D >15 ng/ml. The combination of these five metabolites led to an area under the curve for discrimination for 25(OH)D > 15 ng/ml of 0.82 (95% CI 0.71-0.93). The metabolite pathways related to glutathione metabolism and glutamate metabolism are significantly enriched with regard to vitamin D status.ConclusionVitamin D status is associated with differential metabolic profiles during critical illness. Glutathione and glutamate pathway metabolism, which play principal roles in redox regulation and immunomodulation, respectively, were significantly altered with vitamin D status.

Project description:Antibiotic overuse in poultry husbandry poses a potential threat to meat safety and human health. Lauric acid (LA) is a primary medium-chain fatty acid (MCFA) with a strong antibacterial capacity. The goal of this study was to evaluate the beneficial effects of LA on the growth performance, immune responses, serum metabolism, and cecal microbiota of broiler chickens. One-day-old male Ross 308 broilers were randomly divided into 4 groups: CON, fed a basal diet; ANT, a basal diet supplemented with 75 mg/kg antibiotic; LA500, a basal diet supplemented with 500 mg/kg LA; LA1000, a basal diet supplemented with 1000 mg/kg LA. The feeding period was 42 d. The results showed that LA significantly improved broiler growth and immune functions, as evidenced by increased body weight (BW) and average daily gain (ADG), enhanced intestinal mucosal barrier, upregulated immunoglobulins (IgA, IgM, and IgY), and downregulated inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, and IL-10) (P < 0.05). HPLC/MS-based metabolome analysis revealed that the serum metabolites in the LA group differed from those of CON and ANT groups. LA markedly decreased the abundance of phosphatidylcholines (PCs), increased lysophosphatidylcholines (LysoPCs), and inhibited the sphingolipid metabolism pathway, indicating its capacity to modulate lipid metabolism. 16S rRNA sequencing indicated that LA significantly altered cecal microbiota composition by reducing Phascolarctobacterium, Christensenellaceae_R-7_group, and Bacteroides, and increasing Faecalibacterium and Ruminococcaceae_UCG-014 (P < 0.05). Furthermore, Spearman correlation analysis revealed that changes in metabolism and microbiota were highly correlated with the growth and immune indices; strong links were also found between lipid metabolism and microbial composition. Taken together, LA promotes broiler growth and immune functions by regulating lipid metabolism and gut microbiota. The above findings highlight the substantial potential of LA as a supplement in poultry diets and provide a new strategy to reduce antibiotic usage and improve food safety.

Project description:ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman's rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

Dataset Information

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

Publications

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

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