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15 pages, 1480 KiB

Open AccessArticle

TransDiscovery: Discovering Biotransformation from Human Microbiota by Integrating Metagenomic and Metabolomic Data

by Donghui Yan, Liu Cao, Muqing Zhou and Hosein Mohimani

Metabolites 2022, 12(2), 119; https://doi.org/10.3390/metabo12020119 - 26 Jan 2022

Cited by 2 | Viewed by 3463

Abstract

The human microbiome is a complex community of microorganisms, their enzymes, and the molecules they produce or modify. Recent studies show that imbalances in human microbial ecosystems can cause disease. Our microbiome affects our health through the products of biochemical reactions catalyzed by [...] Read more.

The human microbiome is a complex community of microorganisms, their enzymes, and the molecules they produce or modify. Recent studies show that imbalances in human microbial ecosystems can cause disease. Our microbiome affects our health through the products of biochemical reactions catalyzed by microbial enzymes (microbial biotransformations). Despite their significance, currently, there are no systematic strategies for identifying these chemical reactions, their substrates and molecular products, and their effects on health and disease. We present TransDiscovery, a computational algorithm that integrates molecular networks (connecting related molecules with similar mass spectra), association networks (connecting co-occurring molecules and microbes) and knowledge bases of microbial enzymes to discover microbial biotransformations, their substrates, and their products. After searching the metabolomics and metagenomics data from the American Gut Project and the Global Foodomic Project, TranDiscovery identified 17 potentially novel biotransformations from the human gut microbiome, along with the corresponding microbial species, substrates, and products. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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17 pages, 2950 KiB

Open AccessArticle

Metabolic Fluctuations in the Human Stool Obtained from Blastocystis Carriers and Non-Carriers

by Emma L. Betts, Jamie M. Newton, Gary S. Thompson, Fakhriddin Sarzhanov, Vasana Jinatham, Moon-Ju Kim, Siam Popluechai, Funda Dogruman-Al, Eun-Jeong Won, Eleni Gentekaki and Anastasios D. Tsaousis

Metabolites 2021, 11(12), 883; https://doi.org/10.3390/metabo11120883 - 17 Dec 2021

Cited by 4 | Viewed by 3194

Abstract

Blastocystis is an obligate anaerobic microbial eukaryote that frequently inhabits the gastrointestinal tract. Despite this prevalence, very little is known about the extent of its genetic diversity, pathogenicity, and interaction with the rest of the microbiome and its host. Although the organism is [...] Read more.

Blastocystis is an obligate anaerobic microbial eukaryote that frequently inhabits the gastrointestinal tract. Despite this prevalence, very little is known about the extent of its genetic diversity, pathogenicity, and interaction with the rest of the microbiome and its host. Although the organism is morphologically static, it has no less than 28 genetically distinct subtypes (STs). Reports on the pathogenicity of Blastocystis are conflicting. The association between Blastocystis and intestinal bacterial communities is being increasingly explored. Nonetheless, similar investigations extending to the metabolome are non-existent.Using established NMR metabolomics protocols in 149 faecal samples from individuals from South Korea (n = 38), Thailand (n = 44) and Turkey (n = 69), we have provided a snapshot of the core metabolic compounds present in human stools with (B+) and without (B−) Blastocystis. Samples included hosts with gastrointestinal symptoms and asymptomatics. A total of nine, 62 and 98 significant metabolites were associated with Blastocystis carriage in the South Korean, Thai and Turkish sample sets respectively, with a number of metabolites increased in colonised groups. The metabolic profiles of B+ and B− samples from all countries were distinct and grouped separately in the partial least squares-discriminant analysis (PLS-DA). Typical inflammation-related metabolites negatively associated with Blastocystis positive samples. This data will assist in directing future studies underlying the involvement of Blastocystis in physiological processes of both the gut microbiome and the host. Future studies using metabolome and microbiome data along with host physiology and immune responses information will contribute significantly towards elucidating the role of Blastocystis in health and disease. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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19 pages, 7426 KiB

Open AccessArticle

Antibiotic-Induced Dysbiosis of Microbiota Promotes Chicken Lipogenesis by Altering Metabolomics in the Cecum

by Tao Zhang, Hao Ding, Lan Chen, Yueyue Lin, Yongshuang Gong, Zhiming Pan, Genxi Zhang, Kaizhou Xie, Guojun Dai and Jinyu Wang

Metabolites 2021, 11(8), 487; https://doi.org/10.3390/metabo11080487 - 28 Jul 2021

Cited by 19 | Viewed by 2846

Abstract

Elucidation of the mechanism of lipogenesis and fat deposition is essential for controlling excessive fat deposition in chicken. Studies have shown that gut microbiota plays an important role in regulating host lipogenesis and lipid metabolism. However, the function of gut microbiota in the [...] Read more.

Elucidation of the mechanism of lipogenesis and fat deposition is essential for controlling excessive fat deposition in chicken. Studies have shown that gut microbiota plays an important role in regulating host lipogenesis and lipid metabolism. However, the function of gut microbiota in the lipogenesis of chicken and their relevant mechanisms are poorly understood. In the present study, the gut microbiota of chicken was depleted by oral antibiotics. Changes in cecal microbiota and metabolomics were detected by 16S rRNA sequencing and ultra-high performance liquid chromatography coupled with MS/MS (UHPLC–MS/MS) analysis. The correlation between antibiotic-induced dysbiosis of gut microbiota and metabolites and lipogenesis were analysed. We found that oral antibiotics significantly promoted the lipogenesis of chicken. 16S rRNA sequencing indicated that oral antibiotics significantly reduced the diversity and richness and caused dysbiosis of gut microbiota. Specifically, the abundance of Proteobacteria was increased considerably while the abundances of Bacteroidetes and Firmicutes were significantly decreased. At the genus level, the abundances of genera Escherichia-Shigella and Klebsiella were significantly increased while the abundances of 12 genera were significantly decreased, including Bacteroides. UHPLC-MS/MS analysis showed that antibiotic-induced dysbiosis of gut microbiota significantly altered cecal metabolomics and caused declines in abundance of 799 metabolites and increases in abundance of 945 metabolites. Microbiota-metabolite network revealed significant correlations between 4 differential phyla and 244 differential metabolites as well as 15 differential genera and 304 differential metabolites. Three metabolites of l-glutamic acid, pantothenate acid and N-acetyl-l-aspartic acid were identified as potential metabolites that link gut microbiota and lipogenesis in chicken. In conclusion, our results showed that antibiotic-induced dysbiosis of gut microbiota promotes lipogenesis of chicken by altering relevant metabolomics. The efforts in this study laid a basis for further study of the mechanisms that gut microbiota regulates lipogenesis and fat deposition of chicken. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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20 pages, 6238 KiB

Open AccessArticle

Influence of Extraction Solvent on Nontargeted Metabolomics Analysis of Enrichment Reactor Cultures Performing Enhanced Biological Phosphorus Removal (EBPR)

by Nay Min Min Thaw Saw, Pipob Suwanchaikasem, Rogelio Zuniga-Montanez, Guanglei Qiu, Ezequiel M. Marzinelli, Stefan Wuertz and Rohan B. H. Williams

Metabolites 2021, 11(5), 269; https://doi.org/10.3390/metabo11050269 - 26 Apr 2021

Cited by 6 | Viewed by 2770

Abstract

Metabolome profiling is becoming more commonly used in the study of complex microbial communities and microbiomes; however, to date, little information is available concerning appropriate extraction procedures. We studied the influence of different extraction solvent mixtures on untargeted metabolomics analysis of two continuous [...] Read more.

Metabolome profiling is becoming more commonly used in the study of complex microbial communities and microbiomes; however, to date, little information is available concerning appropriate extraction procedures. We studied the influence of different extraction solvent mixtures on untargeted metabolomics analysis of two continuous culture enrichment communities performing enhanced biological phosphate removal (EBPR), with each enrichment targeting distinct populations of polyphosphate-accumulating organisms (PAOs). We employed one non-polar solvent and up to four polar solvents for extracting metabolites from biomass. In one of the reactor microbial communities, we surveyed both intracellular and extracellular metabolites using the same set of solvents. All samples were analysed using ultra-performance liquid chromatography mass spectrometry (UPLC-MS). UPLC-MS data obtained from polar and non-polar solvents were analysed separately and evaluated using extent of repeatability, overall extraction capacity and the extent of differential abundance between physiological states. Despite both reactors demonstrating the same bioprocess phenotype, the most appropriate extraction method was biomass specific, with methanol: water (50:50 v/v) and methanol: chloroform: water (40:40:20 v/v/v) being chosen as the most appropriate for each of the two different bioreactors, respectively. Our approach provides new data on the influence of solvent choice on the untargeted surveys of the metabolome of PAO enriched EBPR communities and suggests that metabolome extraction methods need to be carefully tailored to the specific complex microbial community under study. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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16 pages, 2727 KiB

Open AccessArticle

Host-Microbiome Interactions Mediated by Phenolic Metabolites in Chronically Critically Ill Patients

by Ekaterina Chernevskaya, Natalia Klimenko, Alisa Pautova, Irina Buyakova, Alexander Tyakht and Natalia Beloborodova

Metabolites 2021, 11(2), 122; https://doi.org/10.3390/metabo11020122 - 20 Feb 2021

Cited by 15 | Viewed by 4285

Abstract

The community structure and metabolic potential of gut microbiome is not well investigated, especially in chronically critically ill patients with prolonged dependence on support systems after severe brain disorders. Microbial phenolic metabolites can target the brain function by the direct and indirect modulation [...] Read more.

The community structure and metabolic potential of gut microbiome is not well investigated, especially in chronically critically ill patients with prolonged dependence on support systems after severe brain disorders. Microbial phenolic metabolites can target the brain function by the direct and indirect modulation of inflammation. The aim of this study was to investigate the features of the gut microbiota and profile of certain metabolites in the progression and reversibility of neurological disorders in chronically critically ill patients. Fecal samples were collected in dynamics from such patients (n = 44) and analyzed using 16S rRNA sequencing. Serum microbial and mitochondrial metabolites were measured by GC-MS and compared with the biomarkers and clinical neurological scores. The identified associations between specific bacterial taxa in fecal samples, neurological status and serum levels of metabolites suggest that impacts on specific members of the gut microbiota and their metabolism might be a promising tool for regulating brain function in future. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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26 pages, 4971 KiB

Open AccessArticle

Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions

by Rafael de Felício, Patricia Ballone, Cristina Freitas Bazzano, Luiz F. G. Alves, Renata Sigrist, Gina Polo Infante, Henrique Niero, Fernanda Rodrigues-Costa, Arthur Zanetti Nunes Fernandes, Luciane A. C. Tonon, Luciana S. Paradela, Renna Karoline Eloi Costa, Sandra Martha Gomes Dias, Andréa Dessen, Guilherme P. Telles, Marcus Adonai Castro da Silva, Andre Oliveira de Souza Lima and Daniela Barretto Barbosa Trivella

Metabolites 2021, 11(2), 107; https://doi.org/10.3390/metabo11020107 - 12 Feb 2021

Cited by 8 | Viewed by 4150

Abstract

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here [...] Read more.

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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19 pages, 8160 KiB

Open AccessArticle

Metabolites from Microbes Isolated from the Skin of the Panamanian Rocket Frog Colostethus panamansis (Anura: Dendrobatidae)

by Christian Martin H., Roberto Ibáñez, Louis-Félix Nothias, Andrés Mauricio Caraballo-Rodríguez, Pieter C. Dorrestein and Marcelino Gutiérrez

Metabolites 2020, 10(10), 406; https://doi.org/10.3390/metabo10100406 - 13 Oct 2020

Cited by 3 | Viewed by 4694

Abstract

The Panamanian rocket frog Colostethus panamansis (family Dendrobatidae) has been affected by chytridiomycosis, a deadly disease caused by the fungus Batrachochytrium dendrobatidis (Bd). While there are still uninfected frogs, we set out to isolate microbes from anatomically distinct regions in an [...] Read more.

The Panamanian rocket frog Colostethus panamansis (family Dendrobatidae) has been affected by chytridiomycosis, a deadly disease caused by the fungus Batrachochytrium dendrobatidis (Bd). While there are still uninfected frogs, we set out to isolate microbes from anatomically distinct regions in an effort to create a cultivable resource within Panama for potential drug/agricultural/ecological applications that perhaps could also be used as part of a strategy to protect frogs from infections. To understand if there are specific anatomies that should be explored in future applications of this resource, we mapped skin-associated bacteria of C. panamansis and their metabolite production potential by mass spectrometry on a 3D model. Our results indicate that five bacterial families (Enterobacteriaceae, Comamonadaceae, Aeromonadaceae, Staphylococcaceae and Pseudomonadaceae) dominate the cultivable microbes from the skin of C. panamansis. The combination of microbial classification and molecular analysis in relation to the anti-Bd inhibitory databases reveals the resource has future potential for amphibian conservation. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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Review

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15 pages, 1183 KiB

Open AccessFeature PaperReview

Linking Gut Microbiome and Lipid Metabolism: Moving beyond Associations

by Santosh Lamichhane, Partho Sen, Marina Amaral Alves, Henrique C. Ribeiro, Peppi Raunioniemi, Tuulia Hyötyläinen and Matej Orešič

Metabolites 2021, 11(1), 55; https://doi.org/10.3390/metabo11010055 - 15 Jan 2021

Cited by 61 | Viewed by 9322

Abstract

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, [...] Read more.

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, only recently, several studies have shown how microbial lipids alter intestinal and circulating lipid concentrations in the host, thus impacting human lipid homeostasis. There is emerging evidence that gut microbial communities play a particularly significant role in the regulation of host cholesterol and sphingolipid homeostasis. Here, we review and discuss recent research focusing on microbe-host-lipid co-metabolism. We also discuss the interplay of human gut microbiota and molecular lipids entering host systemic circulation, and its role in health and disease. Full article

(This article belongs to the Special Issue Microbiome and Metabolome)

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