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Metabolites
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Metabolites: From Physiology to Pathology
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Metabolites: From Physiology to Pathology

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (30 December 2020) | Viewed by 25094

Special Issue Editors

Dr. Marika Cordaro

E-Mail Website
Guest Editor
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy
Interests: physiology; metabolites; inflammation; pathology; neurology
Special Issues, Collections and Topics in MDPI journals
Dr. Rosalba Siracusa

E-Mail Website
Assistant Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Interests: clinical biochemistry; inflammation; oxidative stress; neurodegeneration; natural compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is a pleasure for us, to invite you to submit a review or a research article for publication in the Special Issue entitled “Metabolites: From Physiology to Pathology” for the journal Metabolites (MDPI).

Metabolite activity is a fascinating aspect of cellular metabolism because, through interaction, metabolites serve as direct modulators of biological processes and phenotypes. These findings have already shown the significant impact of metabolites on biological systems. However, more recently, with the advent and evolution of metabolomics technologies, the discovery of active metabolites with the capability to change cell physiology has grown rapidly. These studies highlight the intrinsic biological activity of metabolites and provide new import to the value of metabolomics, as a way to identify metabolites that act as drivers of biological processes and, thus, better understand their physiological role.

This Special Issue will include studies on the role of metabolites, not only as a "simple molecule involved in a physiological reaction" but as a predictive disease biomarker that could be used as a prognostic target in several disorders, metabolic and not. Research articles collecting data from both in vitro and in vivo investigations are welcome. In addition, review articles reporting on metabolites currently used as therapeutic targets or biomarkers would complete the topic.

Dr. Marika Cordaro
Ms. Rosalba Siracusa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecules
  • metabolism
  • physiology
  • pathology
  • inflammation
  • disorders
  • biochemistry
  • biochemical markers

Published Papers (6 papers)

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Research

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14 pages, 1091 KiB  
Article
General Unified Microbiome Profiling Pipeline (GUMPP) for Large Scale, Streamlined and Reproducible Analysis of Bacterial 16S rRNA Data to Predicted Microbial Metagenomes, Enzymatic Reactions and Metabolic Pathways
by Boštjan Murovec, Leon Deutsch and Blaž Stres
Metabolites 2021, 11(6), 336; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11060336 - 24 May 2021
Cited by 1 | Viewed by 6255
Abstract
General Unified Microbiome Profiling Pipeline (GUMPP) was developed for large scale, streamlined and reproducible analysis of bacterial 16S rRNA data and prediction of microbial metagenomes, enzymatic reactions and metabolic pathways from amplicon data. GUMPP workflow introduces reproducible data analyses at each of the [...] Read more.
General Unified Microbiome Profiling Pipeline (GUMPP) was developed for large scale, streamlined and reproducible analysis of bacterial 16S rRNA data and prediction of microbial metagenomes, enzymatic reactions and metabolic pathways from amplicon data. GUMPP workflow introduces reproducible data analyses at each of the three levels of resolution (genus; operational taxonomic units (OTUs); amplicon sequence variants (ASVs)). The ability to support reproducible analyses enables production of datasets that ultimately identify the biochemical pathways characteristic of disease pathology. These datasets coupled to biostatistics and mathematical approaches of machine learning can play a significant role in extraction of truly significant and meaningful information from a wide set of 16S rRNA datasets. The adoption of GUMPP in the gut-microbiota related research enables focusing on the generation of novel biomarkers that can lead to the development of mechanistic hypotheses applicable to the development of novel therapies in personalized medicine. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
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15 pages, 1278 KiB  
Article
Spinal Muscular Atrophy after Nusinersen Therapy: Improved Physiology in Pediatric Patients with No Significant Change in Urine, Serum, and Liquor 1H-NMR Metabolomes in Comparison to an Age-Matched, Healthy Cohort
by Leon Deutsch, Damjan Osredkar, Janez Plavec and Blaž Stres
Metabolites 2021, 11(4), 206; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11040206 - 30 Mar 2021
Cited by 17 | Viewed by 3614
Abstract
Spinal muscular atrophy (SMA) is a genetically heterogeneous group of rare neuromuscular diseases and was until recently the most common genetic cause of death in children. The effects of 2-month nusinersen therapy on urine, serum, and liquor 1H-NMR metabolomes in SMA males and [...] Read more.
Spinal muscular atrophy (SMA) is a genetically heterogeneous group of rare neuromuscular diseases and was until recently the most common genetic cause of death in children. The effects of 2-month nusinersen therapy on urine, serum, and liquor 1H-NMR metabolomes in SMA males and females were not explored yet, especially not in comparison to the urine 1H-NMR metabolomes of matching male and female cohorts. In this prospective, single-centered study, urine, serum, and liquor samples were collected from 25 male and female pediatric patients with SMA before and after 2 months of nusinersen therapy and urine samples from a matching healthy cohort (n = 125). Nusinersen intrathecal application was the first therapy for the treatment of SMA by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Metabolomes were analyzed using targeted metabolomics utilizing 600 MHz 1H-NMR, parametric and nonparametric multivariate statistical analyses, machine learning, and modeling. Medical assessment before and after nusinersen therapy showed significant improvements of movement, posture, and strength according to various medical tests. No significant differences were found in metabolomes before and after nusinersen therapy in urine, serum, and liquor samples using an ensemble of statistical and machine learning approaches. In comparison to a healthy cohort, 1H-NMR metabolomes of SMA patients contained a reduced number and concentration of urine metabolites and differed significantly between males and females as well. Significantly larger data scatter was observed for SMA patients in comparison to matched healthy controls. Machine learning confirmed urinary creatinine as the most significant, distinguishing SMA patients from the healthy cohort. The positive effects of nusinersen therapy clearly preceded or took place devoid of significant rearrangements in the 1H-NMR metabolomic makeup of serum, urine, and liquor. Urine creatinine was successful at distinguishing SMA patients from the matched healthy cohort, which is a simple systemic novelty linking creatinine and SMA to the physiology of inactivity and diabetes, and it facilitates the monitoring of SMA disease in pediatric patients through non-invasive urine collection. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
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16 pages, 4520 KiB  
Article
The Importance of Objective Stool Classification in Fecal 1H-NMR Metabolomics: Exponential Increase in Stool Crosslinking Is Mirrored in Systemic Inflammation and Associated to Fecal Acetate and Methionine
by Leon Deutsch and Blaz Stres
Metabolites 2021, 11(3), 172; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11030172 - 16 Mar 2021
Cited by 8 | Viewed by 2926
Abstract
Past studies strongly connected stool consistency—as measured by Bristol Stool Scale (BSS)—with microbial gene richness and intestinal inflammation, colonic transit time and metabolome characteristics that are of clinical relevance in numerous gastro intestinal conditions. While retention time, defecation rate, BSS but not water [...] Read more.
Past studies strongly connected stool consistency—as measured by Bristol Stool Scale (BSS)—with microbial gene richness and intestinal inflammation, colonic transit time and metabolome characteristics that are of clinical relevance in numerous gastro intestinal conditions. While retention time, defecation rate, BSS but not water activity have been shown to account for BSS-associated inflammatory effects, the potential correlation with the strength of a gel in the context of intestinal forces, abrasion, mucus imprinting, fecal pore clogging remains unexplored as a shaping factor for intestinal inflammation and has yet to be determined. Our study introduced a minimal pressure approach (MP) by probe indentation as measure of stool material crosslinking in fecal samples. Results reported here were obtained from 170 samples collected in two independent projects, including males and females, covering a wide span of moisture contents and BSS. MP values increased exponentially with increasing consistency (i.e., lower BSS) and enabled stratification of samples exhibiting mixed BSS classes. A trade-off between lowest MP and highest dry matter content delineated the span of intermediate healthy density of gel crosslinks. The crossectional transects identified fecal surface layers with exceptionally high MP and of <5 mm thickness followed by internal structures with an order of magnitude lower MP, characteristic of healthy stool consistency. The MP and BSS values reported in this study were coupled to reanalysis of the PlanHab data and fecal 1H-NMR metabolomes reported before. The exponential association between stool consistency and MP determined in this study was mirrored in the elevated intestinal and also systemic inflammation and other detrimental physiological deconditioning effects observed in the PlanHab participants reported before. The MP approach described in this study can be used to better understand fecal hardness and its relationships to human health as it provides a simple, fine scale and objective stool classification approach for the characterization of the exact sampling locations in future microbiome and metabolome studies. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
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31 pages, 5743 KiB  
Article
Metabolomes and Lipidomes of the Infective Stages of the Gastrointestinal nematodes, Nippostrongylus brasiliensis and Trichuris muris
by Karma Yeshi, Darren J. Creek, Dovile Anderson, Edita Ritmejerytė, Luke Becker, Alex Loukas and Phurpa Wangchuk
Metabolites 2020, 10(11), 446; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10110446 - 06 Nov 2020
Cited by 14 | Viewed by 3400
Abstract
Soil-transmitted helminths, including hookworms and whipworms, infect billions of people worldwide. Their capacity to penetrate and migrate through their hosts’ tissues is influenced by the suite of molecules produced by the infective developmental stages. To facilitate a better understanding of the immunobiology and [...] Read more.
Soil-transmitted helminths, including hookworms and whipworms, infect billions of people worldwide. Their capacity to penetrate and migrate through their hosts’ tissues is influenced by the suite of molecules produced by the infective developmental stages. To facilitate a better understanding of the immunobiology and pathogenicity of human hookworms and whipworms, we investigated the metabolomes of the infective stage of Nippostrongylus brasiliensis third-stage larvae (L3) which penetrate the skin and Trichuris muris eggs which are orally ingested, using untargeted liquid chromatography-mass spectrometry (LC-MS). We identified 55 polar metabolites through Metabolomics Standard Initiative level-1 (MSI-I) identification from N. brasiliensis and T. muris infective stages, out of which seven were unique to excretory/secretory products (ESPs) of N. brasiliensis L3. Amino acids were a principal constituent (33 amino acids). Additionally, we identified 350 putative lipids, out of which 28 (all known lipids) were unique to N. brasiliensis L3 somatic extract and four to T. muris embryonated egg somatic extract. Glycerophospholipids and glycerolipids were the major lipid groups. The catalogue of metabolites identified in this study shed light on the biology, and possible therapeutic and diagnostic targets for the treatment of these critical infectious pathogens. Moreover, with the growing body of literature on the therapeutic utility of helminth ESPs for treating inflammatory diseases, a role for metabolites is likely but has received little attention thus far. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
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16 pages, 3563 KiB  
Article
Characterization of Sunflower Oil Extracts from the Lichen Usnea barbata
by Shereen Basiouni, Marwa A. A. Fayed, Reda Tarabees, Mohamed El-Sayed, Ahmed Elkhatam, Klaus-Rainer Töllner, Manfred Hessel, Thomas Geisberger, Claudia Huber, Wolfgang Eisenreich and Awad A. Shehata
Metabolites 2020, 10(9), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10090353 - 31 Aug 2020
Cited by 16 | Viewed by 3604
Abstract
The increasing global emergence of multidrug resistant (MDR) pathogens is categorized as one of the most important health problems. Therefore, the discovery of novel antimicrobials is of the utmost importance. Lichens provide a rich source of natural products including unique polyketides and polyphenols. [...] Read more.
The increasing global emergence of multidrug resistant (MDR) pathogens is categorized as one of the most important health problems. Therefore, the discovery of novel antimicrobials is of the utmost importance. Lichens provide a rich source of natural products including unique polyketides and polyphenols. Many of them display pharmaceutical benefits. The aim of this study was directed towards the characterization of sunflower oil extracts from the fruticose lichen, Usnea barbata. The concentration of the major polyketide, usnic acid, was 1.6 mg/mL extract as determined by NMR analysis of the crude mixture corresponding to 80 mg per g of the dried lichen. The total phenolics and flavonoids were determined by photometric assays as 4.4 mg/mL (gallic acid equivalent) and 0.27 mg/mL (rutin equivalent) corresponding to 220 mg/g and 13.7 mg/g lichen, respectively. Gram-positive (e.g., Enterococcus faecalis) and Gram-negative bacteria, as well as clinical isolates of infected chickens were sensitive against these extracts as determined by agar diffusion tests. Most of these activities increased in the presence of zinc salts. The data suggest the potential usage of U. barbata extracts as natural additives and mild antibiotics in animal husbandry, especially against enterococcosis in poultry. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
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Review

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19 pages, 1120 KiB  
Review
Involvements of Hyperhomocysteinemia in Neurological Disorders
by Marika Cordaro, Rosalba Siracusa, Roberta Fusco, Salvatore Cuzzocrea, Rosanna Di Paola and Daniela Impellizzeri
Metabolites 2021, 11(1), 37; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11010037 - 06 Jan 2021
Cited by 26 | Viewed by 4408
Abstract
Homocysteine (HCY), a physiological amino acid formed when proteins break down, leads to a pathological condition called hyperhomocysteinemia (HHCY), when it is over a definite limit. It is well known that an increase in HCY levels in blood, can contribute to arterial damage [...] Read more.
Homocysteine (HCY), a physiological amino acid formed when proteins break down, leads to a pathological condition called hyperhomocysteinemia (HHCY), when it is over a definite limit. It is well known that an increase in HCY levels in blood, can contribute to arterial damage and several cardiovascular disease, but the knowledge about the relationship between HCY and brain disorders is very poor. Recent studies demonstrated that an alteration in HCY metabolism or a deficiency in folate or vitamin B12 can cause altered methylation and/or redox potentials, that leads to a modification on calcium influx in cells, or into an accumulation in amyloid and/or tau protein involving a cascade of events that culminate in apoptosis, and, in the worst conditions, neuronal death. The present review will thus summarize how much is known about the possible role of HHCY in neurodegenerative disease. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
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