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11 pages, 2214 KiB

Open AccessArticle

Untargeted Microbial Exometabolomics and Metabolomics Analysis of Helicobacter pylori J99 and jhp0106 Mutant

by Cheng-Yen Kao, Pei-Yun Kuo and Hsiao-Wei Liao

Metabolites 2021, 11(12), 808; https://doi.org/10.3390/metabo11120808 - 28 Nov 2021

Cited by 6 | Viewed by 2386

Abstract

Untargeted metabolomic profiling provides the opportunity to comprehensively explore metabolites of interest. Herein, we investigated the metabolic pathways associated with Jhp0106, a glycosyltransferase enzyme in Helicobacter pylori. Through untargeted exometabolomic and metabolomic profiling, we identified 9 and 10 features with significant differences [...] Read more.

Untargeted metabolomic profiling provides the opportunity to comprehensively explore metabolites of interest. Herein, we investigated the metabolic pathways associated with Jhp0106, a glycosyltransferase enzyme in Helicobacter pylori. Through untargeted exometabolomic and metabolomic profiling, we identified 9 and 10 features with significant differences in the culture media and pellets of the wild-type (WT) J99 and jhp0106 mutant (Δjhp0106). After tentative identification, several phosphatidylethanolamines (PEs) were identified in the culture medium, the levels of which were significantly higher in WT J99 than in Δjhp0106. Moreover, the reduced lysophosphatidic acid absorption from the culture medium and the reduced intrinsic diacylglycerol levels observed in Δjhp0106 indicate the possibility of reduced PE synthesis in Δjhp0106. The results suggest an association of the PE synthesis pathway with flagellar formation in H. pylori. Further investigations should be conducted to confirm this finding and the roles of the PE synthesis pathway in flagellar formation. This study successfully demonstrates the feasibility of the proposed extraction procedure and untargeted exometabolomic and metabolomic profiling strategies for microbial metabolomics. They may also extend our understanding of metabolic pathways associated with flagellar formation in H. pylori. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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13 pages, 1650 KiB

Open AccessFeature PaperArticle

Chronic Effect of a Cafeteria Diet and Intensity of Resistance Training on the Circulating Lysophospholipidome in Young Rats

by Susana Suárez-García, Antoni Caimari, Josep M. del Bas, Jaume Lalanza, Rosa M. Escorihuela, Manuel Suárez, Cristina Torres-Fuentes and Lluís Arola

Metabolites 2021, 11(8), 471; https://doi.org/10.3390/metabo11080471 - 22 Jul 2021

Viewed by 2348

Abstract

The daily practice of physical exercise and a balanced diet are recommended to prevent metabolic syndrome (MetS). As MetS is a multifactorial disorder associated with the development of serious diseases, the advancement of comprehensive biomarkers could aid in an accurate diagnosis. In this [...] Read more.

The daily practice of physical exercise and a balanced diet are recommended to prevent metabolic syndrome (MetS). As MetS is a multifactorial disorder associated with the development of serious diseases, the advancement of comprehensive biomarkers could aid in an accurate diagnosis. In this regard, it is known that gut microbiota is altered in MetS, and especially, lipid metabolites species are highly modified, thus emerging as potential biomarkers. In preliminary studies, we observed that alterations in serum lysoglycerophospholipids (Lyso-PLs) were shared between animals with diet-induced MetS and those performing resistance exercises assiduously. Therefore, our objective was the targeted determination of the lysophospholipidome in young rats fed a standard (ST) or a cafeteria diet (CAF) and submitted to different training intensities to evaluate its potential as a biomarker of a detrimental lifestyle. Targeted metabolomics focused on lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs) and multivariate statistics were used to achieve an integral understanding. Chronic intake of CAF altered the serological levels of both lipid subclasses. Twenty-two Lyso-PLs were significantly altered by CAF, from which we selected Lyso-PCs (14:0), (17:1) and (20:2) and Lyso-PEs (18:2) and (18:3) as they were enough to achieve an optimal prediction. The main effect of physical training was decreased Lyso-PEs levels with disparities among training intensities for each diet. We concluded that an examination of the lysophospholipidome reveals the general state of the metabolome in young female rats, especially due to intake of an MetS-inducing diet, thus highlighting the importance of this family of compounds in lipid disorders. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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27 pages, 5091 KiB

Open AccessArticle

by Mihai V. Curtasu, Valeria Tafintseva, Zachary A. Bendiks, Maria L. Marco, Achim Kohler, Yetong Xu, Natalja P. Nørskov, Helle Nygaard Lærke, Knud Erik Bach Knudsen and Mette Skou Hedemann

Metabolites 2020, 10(11), 456; https://doi.org/10.3390/metabo10110456 - 12 Nov 2020

Cited by 17 | Viewed by 4975

Abstract

The metabolome and gut microbiota were investigated in a juvenile Göttingen minipig model. This study aimed to explore the metabolic effects of two carbohydrate sources with different degrees of risk in obesity development when associated with a high fat intake. A high-risk (HR) [...] Read more.

The metabolome and gut microbiota were investigated in a juvenile Göttingen minipig model. This study aimed to explore the metabolic effects of two carbohydrate sources with different degrees of risk in obesity development when associated with a high fat intake. A high-risk (HR) high-fat diet containing 20% fructose was compared to a control lower-risk (LR) high-fat diet where a similar amount of carbohydrate was provided as a mix of digestible and resistant starch from high amylose maize. Both diets were fed ad libitum. Non-targeted metabolomics was used to explore plasma, urine, and feces samples over five months. Plasma and fecal short-chain fatty acids were targeted and quantified. Fecal microbiota was analyzed using genomic sequencing. Data analysis was performed using sparse multi-block partial least squares regression. The LR diet increased concentrations of fecal and plasma total short-chain fatty acids, primarily acetate, and there was a higher relative abundance of microbiota associated with acetate production such as Bacteroidetes and Ruminococcus. A higher proportion of Firmicutes was measured with the HR diet, together with a lower alpha diversity compared to the LR diet. Irrespective of diet, the ad libitum exposure to the high-energy diets was accompanied by well-known biomarkers associated with obesity and diabetes, particularly branched-chain amino acids, keto acids, and other catabolism metabolites. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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15 pages, 1589 KiB

Open AccessArticle

Rapid Preparation of a Large Sulfated Metabolite Library for Structure Validation in Human Samples

by Mario S. P. Correia, Weifeng Lin, Arash J. Aria, Abhishek Jain and Daniel Globisch

Metabolites 2020, 10(10), 415; https://doi.org/10.3390/metabo10100415 - 16 Oct 2020

Cited by 9 | Viewed by 3979

Abstract

Metabolomics analysis of biological samples is widely applied in medical and natural sciences. Assigning the correct chemical structure in the metabolite identification process is required to draw the correct biological conclusions and still remains a major challenge in this research field. Several metabolite [...] Read more.

Metabolomics analysis of biological samples is widely applied in medical and natural sciences. Assigning the correct chemical structure in the metabolite identification process is required to draw the correct biological conclusions and still remains a major challenge in this research field. Several metabolite tandem mass spectrometry (MS/MS) fragmentation spectra libraries have been developed that are either based on computational methods or authentic libraries. These libraries are limited due to the high number of structurally diverse metabolites, low commercial availability of these compounds, and the increasing number of newly discovered metabolites. Phase II modification of xenobiotics is a compound class that is underrepresented in these databases despite their importance in diet, drug, or microbiome metabolism. The O-sulfated metabolites have been described as a signature for the co-metabolism of bacteria and their human host. Herein, we have developed a straightforward chemical synthesis method for rapid preparation of sulfated metabolite standards to obtain mass spectrometric fragmentation pattern and retention time information. We report the preparation of 38 O-sulfated alcohols and phenols for the determination of their MS/MS fragmentation pattern and chromatographic properties. Many of these metabolites are regioisomers that cannot be distinguished solely by their fragmentation pattern. We demonstrate that the versatility of this method is comparable to standard chemical synthesis. This comprehensive metabolite library can be applied for co-injection experiments to validate metabolites in different human sample types to explore microbiota-host co-metabolism, xenobiotic, and diet metabolism. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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7 pages, 583 KiB

Open AccessCommunication

Microbial Metabolite Urolithin B Inhibits Recombinant Human Monoamine Oxidase A Enzyme

by Rajbir Singh, Sandeep Chandrashekharappa, Praveen Kumar Vemula, Bodduluri Haribabu and Venkatakrishna Rao Jala

Metabolites 2020, 10(6), 258; https://doi.org/10.3390/metabo10060258 - 19 Jun 2020

Cited by 17 | Viewed by 3632

Abstract

Urolithins are gut microbial metabolites derived from ellagitannins (ET) and ellagic acid (EA), and shown to exhibit anticancer, anti-inflammatory, anti-microbial, anti-glycative and anti-oxidant activities. Similarly, the parent molecules, ET and EA are reported for their neuroprotection and antidepressant activities. Due to the poor [...] Read more.

Urolithins are gut microbial metabolites derived from ellagitannins (ET) and ellagic acid (EA), and shown to exhibit anticancer, anti-inflammatory, anti-microbial, anti-glycative and anti-oxidant activities. Similarly, the parent molecules, ET and EA are reported for their neuroprotection and antidepressant activities. Due to the poor bioavailability of ET and EA, the in vivo functional activities cannot be attributed exclusively to these compounds. Elevated monoamine oxidase (MAO) activities are responsible for the inactivation of monoamine neurotransmitters in neurological disorders, such as depression and Parkinson’s disease. In this study, we examined the inhibitory effects of urolithins (A, B and C) and EA on MAO activity using recombinant human MAO-A and MAO-B enzymes. Urolithin B was found to be a better MAO-A enzyme inhibitor among the tested urolithins and EA with an IC₅₀ value of 0.88 µM, and displaying a mixed mode of inhibition. However, all tested compounds exhibited higher IC₅₀ (>100 µM) for MAO-B enzyme. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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Review

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23 pages, 388 KiB

Open AccessReview

Exploring the Gut Microbiota and Cardiovascular Disease

by Kiera Murphy, Aoife N. O’Donovan, Noel M. Caplice, R. Paul Ross and Catherine Stanton

Metabolites 2021, 11(8), 493; https://doi.org/10.3390/metabo11080493 - 29 Jul 2021

Cited by 33 | Viewed by 5668

Abstract

Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated [...] Read more.

Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated with the development and progression of numerous disease states, including CVD. The gut microbiota are involved in the production of several metabolites, such as short-chain fatty acids (SCFAs), bile acids and trimethylamine-N-oxide (TMAO). These products of microbial metabolism are important modulatory factors and have been associated with an increased risk of CVD. Due to its association with CVD development, the gut microbiota has emerged as a target for therapeutic approaches. In this review, we summarise the current knowledge on the role of the gut microbiome in CVD development, and associated microbial communities, functions, and metabolic profiles. We also discuss CVD therapeutic interventions that target the gut microbiota such as probiotics and faecal microbiota transplantation. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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20 pages, 1367 KiB

Open AccessReview

Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis

by Aravind Thavamani, Iman Salem, Thomas J. Sferra and Senthilkumar Sankararaman

Metabolites 2021, 11(2), 123; https://doi.org/10.3390/metabo11020123 - 22 Feb 2021

Cited by 37 | Viewed by 4271

Abstract

Cystic fibrosis (CF) is the most common lethal, multisystemic genetic disorder in Caucasians. Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) protein are responsible for impairment of epithelial anionic transport, leading to impaired fluid regulation and pH imbalance across multiple [...] Read more.

Cystic fibrosis (CF) is the most common lethal, multisystemic genetic disorder in Caucasians. Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) protein are responsible for impairment of epithelial anionic transport, leading to impaired fluid regulation and pH imbalance across multiple organs. Gastrointestinal (GI) manifestations in CF may begin in utero and continue throughout the life, resulting in a chronic state of an altered intestinal milieu. Inherent dysfunction of CFTR leads to dysbiosis of the gut. This state of dysbiosis is further perpetuated by acquired factors such as use of antibiotics for recurrent pulmonary exacerbations. Since the gastrointestinal microbiome and their metabolites play a vital role in nutrition, metabolic, inflammatory, and immune functions, the gut dysbiosis will in turn impact various manifestations of CF—both GI and extra-GI. This review focuses on the consequences of gut dysbiosis and its metabolic implications on CF disease and possible ways to restore homeostasis. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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22 pages, 1451 KiB

Open AccessReview

The Impact of Microbiota on the Pathogenesis of Amyotrophic Lateral Sclerosis and the Possible Benefits of Polyphenols. An Overview

by Julia Casani-Cubel, María Benlloch, Claudia Emmanuela Sanchis-Sanchis, Raquel Marin, Jose María Lajara-Romance and Jose Enrique de la Rubia Orti

Metabolites 2021, 11(2), 120; https://doi.org/10.3390/metabo11020120 - 20 Feb 2021

Cited by 17 | Viewed by 4612

Abstract

The relationship between gut microbiota and neurodegenerative diseases is becoming clearer. Among said diseases amyotrophic lateral sclerosis (ALS) stands out due to its severity and, as with other chronic pathologies that cause neurodegeneration, gut microbiota could play a fundamental role in its pathogenesis. [...] Read more.

The relationship between gut microbiota and neurodegenerative diseases is becoming clearer. Among said diseases amyotrophic lateral sclerosis (ALS) stands out due to its severity and, as with other chronic pathologies that cause neurodegeneration, gut microbiota could play a fundamental role in its pathogenesis. Therefore, polyphenols could be a therapeutic alternative due to their anti-inflammatory action and probiotic effect. Thus, the objective of our narrative review was to identify those bacteria that could have connection with the mentioned disease (ALS) and to analyze the benefits produced by administering polyphenols. Therefore, an extensive search was carried out selecting the most relevant articles published between 2005 and 2020 on the PubMed and EBSCO database on research carried out on cell, animal and human models of the disease. Thereby, after selecting, analyzing and debating the main articles on this topic, the bacteria related to the pathogenesis of ALS have been identified, among which we can positively highlight the presence mainly of Akkermansia muciniphila, but also Lactobacillus spp., Bifidobacterium spp. or Butyrivibrio fibrisolvens. Nevertheless, the presence of Escherichia coli or Ruminococcus torques stand out negatively for the disease. In addition, most of these bacteria are associated with molecular changes also linked to the pathogenesis of ALS. However, once the main polyphenols related to improvements in any of these three ALS models were assessed, many of them show positive results that could improve the prognosis of the disease. Nonetheless, epigallocatechin gallate (EGCG), curcumin and resveratrol are the polyphenols considered to show the most promising results as a therapeutic alternative for ALS through changes in microbiota. Full article

(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)

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