Comparative Analysis of Host Metabolic Alterations in Murine Malaria Models with Uncomplicated or Severe Malaria

Das, Aleena; Sahu, Welka; Ojha, Deepak; Reddy, K. Sony; Suar, Mrutyunjay

doi:10.1021/acs.jproteome.2c00123

Cited by 3 publications

(1 citation statement)

References 86 publications

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“…A metabolomics study found that human malarial infections are associated with the presence of elevated amounts of bile acids, bile pigments, and steroid hormones. Upregulated levels of metabolites such as histidine, ornithine, pantothenate, phenylalanine, pipecolate and valine were observed in individuals with severe malaria (Das et al, 2022). In addition, serum metabolic analysis of mice infected with T. gondii revealed changes in glycerophospholipid metabolism, amino acid biosynthesis, and tyrosine metabolism (Zhou et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

Shen¹,

Wang²,

Han³

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionThe protozoan parasite Babesia microti is the primary cause of human babesiosis. This parasite invades and multiplies inside red blood cells (RBCs), and infections differ significantly based on the age and immune competency of the host. The aim of this study was to investigate the use of serum metabolic profiling to identify systemic metabolic variations between B. microti-infected mice and noninfected controls.MethodsA serum metabolomics analysis of BALB/c mice that had been intraperitoneally injected with 107B. microti-infected RBCs was performed. Serum samples from the early infected group (2 days postinfection), the acutely infected group (9 days postinfection), and the noninfected group were collected and evaluated using a liquid chromatography−mass spectrometry (LC−MS) platform. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) identified metabolomic profiles that differentiated the B. microti-infected and noninfected groups.ResultsOur results confirm that the serum metabolome is significantly influenced by acute B. microti infection and show that infection results in dysregulation of metabolic pathways and perturbation of metabolites. Acutely infected mice displayed perturbations in metabolites associated with taurine and hypotaurine metabolism, histidine metabolism, and arachidonic acid metabolism. Taurocholic acid, anserine, and arachidonic acid may be potential candidates as serological biomarkers for diagnosing B. microti infection at the acute stage. These metabolites could be further examined for their role in disease complexity.DiscussionOur findings demonstrate that the acute stage of B. microti infection induces abnormalities in the metabolites present in mouse serum and provide new insight into the mechanisms involved in systemic metabolic changes that occur during B. microti infection.

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Section: Introductionmentioning

confidence: 99%

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

Shen¹,

Wang²,

Han³

et al. 2023

Front. Cell. Infect. Microbiol.

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Hormones in malaria infection: influence on disease severity, host physiology, and therapeutic opportunities

Das,

Suar,

Reddy

2024

Bioscience Reports

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Human malaria, caused by Plasmodium parasites, is a fatal disease that disrupts the host’s physiological balance and affects the neuroendocrine system. This review explores how malaria influences and is influenced by hormones. Malaria activates the Hypothalamus-Pituitary-Adrenal axis, leading to increased cortisol, aldosterone, and epinephrine. Cortisol, while reducing inflammation, aids parasite survival, whereas epinephrine helps manage hypoglycemia. The Hypothalamus-Pituitary-Gonad and Hypothalamus-Pituitary-Thyroid axes are also impacted, resulting in lower sex and thyroid hormone levels. Malaria disrupts the renin-angiotensin-aldosterone system (RAAS), causing higher angiotensin-II and aldosterone levels, contributing to edema, hyponatremia and hypertension. Malaria-induced anemia is exacerbated by increased hepcidin, which impairs iron absorption, reducing both iron availability for the parasite and red blood cell formation, despite elevated erythropoietin. Hypoglycemia is common due to decreased glucose production and hyperinsulinemia, although some cases show hyperglycemia due to stress hormones and inflammation. Hypocalcemia, and hypophosphatemia are associated with low Vitamin D3 and parathyroid hormone but high calcitonin. Hormones such as DHEA, melatonin, PTH, Vitamin D3, hepcidin, progesterone, and erythropoietin protects against malaria. Furthermore, synthetic analogs, receptor agonists and antagonists or mimics of hormones like DHEA, melatonin, serotonin, PTH, vitamin D3, estrogen, progesterone, angiotensin, and somatostatin are being explored as potential antimalarial treatments or adjunct therapies. Additionally, hormones like leptin and PCT are being studied as probable markers of malaria infection.

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Growth performance, bile acid profile, fecal microbiome and serum metabolomics of growing-finishing pigs fed diets with bile acids supplementation

Zhou,

Yan,

Zhang

et al. 2023

Journal of Animal Science

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The present experiment was conducted to determine the effect of bile acids (BAs) supplementation on growth performance, BAs profile, fecal microbiome, and serum metabolomics in growing-finishing pigs. A total of 60 pigs [Duroc × (Landrace × Yorkshire)] with an average body weight of 27.0 ± 1.5 kg were selected and allotted into one of 2 groups (castrated male to female ratio = 1:1), with 10 replicates per treatment and 3 pigs per replicate. The 2 treatments were the control group (control) and a porcine bile extract-supplemented group dosed at 0.5 g/kg feed (BA). After a 16-wk treatment, growth performance, BAs profiles in serum and feces, and fecal microbial composition were determined. An untargeted metabolomics approach using gas chromatography with a time-of-flight mass spectrometer was conducted to identify the metabolic pathways and associated metabolites in the serum of pigs. We found that BAs supplementation had no effect on the growth performance of the growing-finishing pig. However, it tended to increase the gain-to-feed ratio for the whole period (P = 0.07). BAs supplementation resulted in elevated serum concentrations of secondary bile acids, including hyodeoxycholic acid (HDCA), glycoursodeoxycholic acid, and tauro-hyodeoxycholic acid, as well as fecal concentration of HDCA (P < 0.05). Fecal microbiota analysis revealed no differences in alpha and beta diversity indices or the relative abundance of operational taxonomic units (OTUs) at both phylum and genus levels between groups. Metabolic pathway analysis revealed that the differential metabolites between control and BA groups are mainly involved in purine metabolism, ether lipid metabolism, glycerophospholipid metabolism, and amino sugar and nucleotide sugar metabolism, as well as primary bile acid biosynthesis. Our findings indicate that BAs supplementation tended to improve the feed efficiency, and significantly altered the BA profile in the serum and feces of growing-finished pigs, regardless of any changes in the gut microbial composition. The altered metabolic pathways could potentially play a vital role in improving the feed efficiency of growing-finished pigs with BAs supplementation.

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Comparative Analysis of Host Metabolic Alterations in Murine Malaria Models with Uncomplicated or Severe Malaria

Cited by 3 publications

References 86 publications

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

Hormones in malaria infection: influence on disease severity, host physiology, and therapeutic opportunities

Growth performance, bile acid profile, fecal microbiome and serum metabolomics of growing-finishing pigs fed diets with bile acids supplementation

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