Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

Abstract

Abstract:Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate.

Perioperative Neurocognitive Disorder

“…In contrast, it has been a popular organism to understand the genetic determinants of general anesthetic sensitivity, 60,61 and more recently it is being used to understand polytrauma and sepsis. 62,63 The advantages are its easy husbandry, fully understood genetics, large numbers of readily available variants, short generation and life span, and lack of regulatory oversight. While the administration of volatile anesthetics is straightforward, the administration of injectable drugs is not.…”

Retracted Article: A high-throughput metabolomics strategy for discovering the influence of differential metabolites and metabolic pathways of huaxian capsules on sepsis-associated Qi deficiency and blood stasis syndrome

“…Some studies reported that sepsis survivors exhibited a metabolic signature, characterized by the decreased level of glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. [15][16][17] The combined approach of high-throughput techniques contribute to revealing the hidden features of sepsis. The main aim of our study is to preliminarily discuss the capability of the metabolomics approach and explore the molecular mechanism in order to treat SQBS in rats, with an attempt to bring new ideas and fundamental reference material for the future sepsis clinical treatment.…”

Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis

“…Yet, it should be noted that this increase was effectively recovered after MaR1 treatment. Bakalov et al [31] reported that a reduced acetate level may be a metabolic feature in a Drosophila melanogaster model of surviving sepsis. Taken together, the recovery of pyruvate metabolism induced by MaR1 treatment could be contributed to its potential therapeutic effect in CLP-induced septic mice.…”