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Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances
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Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (5 October 2023) | Viewed by 22409

Special Issue Editor

Dr. Valeria D’Argenio

E-Mail Website
Guest Editor
1. Department of Human Sciences and Quality of Life Promotion, San Raffaele Open University, Via di Val Cannuta 247, 00166 Rome, Italy
2. CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy
Interests: next generation sequencing; genomics; cancer genomics; hereditary cancers; metagenomics; human microbiome; molecular diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The human microbiota has gained increasing attention as a possible player contributing to the acquisition and maintenance of good health in humans in addition to disease development. Indeed, these microbial communities, living in equilibrium with the human host, are involved in different physiological functions, including immune system development, tolerance acquisition and mucosal permeability establishment. Accordingly, microbial dysbiosis has been highlighted in several diseases that are not limited to gastrointestinal conditions but extend to other organs that are influenced by local resident microbiota and/or gut microbiota. These accumulating data are providing novel clues regarding disease pathogenesis and may open the way to the use of microbial signatures as novel biomarkers for disease monitoring and diagnosis as well as novel targets to develop specific therapies. Nevertheless, most of the current knowledge is based on observational studies: there is a need to move to a more mechanistic approach to unravel the role of microbial dysbiosis in specific diseases. Technological advances, involving both molecular strategies and bioinformatic tools, will be crucial to further improving metagenomic studies and our comprehension of microbial involvement in human well-being.

In this scenario, Genes has decided to dedicate a Special Issue to the role of the human microbiota in health and disease status that will focus on the most recent advancements in this field and support harmonization and improvement of outcomes in this important field.

The intent of this Special Issue is to specifically highlight the most recent advances in metagenomic studies that report not only microbial imbalance in specific diseases but also the molecular mechanisms linking microbes to the development of various pathologies. Research and review articles on these aspects are encouraged. We invite you to take part in this Special Issue with a scientific contribution. The manuscripts will, as always, be subjected to examination by specialized reviewers to guarantee their scientific acceptability.

Dr. Valeria D’Argenio
Guest Editor

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. Genes 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 2600 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

  • microbiota
  • metagenomics
  • microbiota-related diseases
  • microbial dysbiosis
  • microbiota manipulation

Published Papers (7 papers)

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Research

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13 pages, 1979 KiB  
Article
Metagenomics Reveals Specific Microbial Features in Males with Semen Alterations
by Iolanda Veneruso, Federica Cariati, Carlo Alviggi, Lucio Pastore, Rossella Tomaiuolo and Valeria D’Argenio
Genes 2023, 14(6), 1228; https://doi.org/10.3390/genes14061228 - 06 Jun 2023
Cited by 4 | Viewed by 1329
Abstract
Infertility incidence is rising worldwide, with male infertility accounting for about 50% of cases. To date, several factors have been associated with male infertility; in particular, it has been suggested that semen microbiota may play a role. Here, we report the NGS-based analyses [...] Read more.
Infertility incidence is rising worldwide, with male infertility accounting for about 50% of cases. To date, several factors have been associated with male infertility; in particular, it has been suggested that semen microbiota may play a role. Here, we report the NGS-based analyses of 20 semen samples collected from men with (Case) and without (Control) semen alterations. Genomic DNA was extracted from each collected sample, and a specific PCR was carried out to amplify the V4-V6 regions of the 16S rRNA. Sequence reactions were carried out on the MiSeq and analyzed by specific bioinformatic tools. We found a reduced richness and evenness in the Case versus the Control group. Moreover, specific genera, the Mannheimia, the Escherichia_Shigella, and the Varibaculum, were significantly increased in the Case compared to the Control group. Finally, we highlighted a correlation between the microbial profile and semen hyperviscosity. Even if further studies are required on larger groups of subjects to confirm these findings and explore mechanistic hypotheses, our results confirm the correlation between semen features and seminal microbiota. These data, in turn, may open the way to the possible use of semen microbiota as an attractive target for developing novel strategies for infertility management. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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34 pages, 7541 KiB  
Article
Comparison of Metagenomics and Metatranscriptomics Tools: A Guide to Making the Right Choice
by Laura C. Terrón-Camero, Fernando Gordillo-González, Eduardo Salas-Espejo and Eduardo Andrés-León
Genes 2022, 13(12), 2280; https://doi.org/10.3390/genes13122280 - 03 Dec 2022
Cited by 9 | Viewed by 8643
Abstract
The study of microorganisms is a field of great interest due to their environmental (e.g., soil contamination) and biomedical (e.g., parasitic diseases, autism) importance. The advent of revolutionary next-generation sequencing techniques, and their application to the hypervariable regions of the 16S, 18S or [...] Read more.
The study of microorganisms is a field of great interest due to their environmental (e.g., soil contamination) and biomedical (e.g., parasitic diseases, autism) importance. The advent of revolutionary next-generation sequencing techniques, and their application to the hypervariable regions of the 16S, 18S or 23S ribosomal subunits, have allowed the research of a large variety of organisms more in-depth, including bacteria, archaea, eukaryotes and fungi. Additionally, together with the development of analysis software, the creation of specific databases (e.g., SILVA or RDP) has boosted the enormous growth of these studies. As the cost of sequencing per sample has continuously decreased, new protocols have also emerged, such as shotgun sequencing, which allows the profiling of all taxonomic domains in a sample. The sequencing of hypervariable regions and shotgun sequencing are technologies that enable the taxonomic classification of microorganisms from the DNA present in microbial communities. However, they are not capable of measuring what is actively expressed. Conversely, we advocate that metatranscriptomics is a “new” technology that makes the identification of the mRNAs of a microbial community possible, quantifying gene expression levels and active biological pathways. Furthermore, it can be also used to characterise symbiotic interactions between the host and its microbiome. In this manuscript, we examine the three technologies above, and discuss the implementation of different software and databases, which greatly impact the obtaining of reliable results. Finally, we have developed two easy-to-use pipelines leveraging Nextflow technology. These aim to provide everything required for an average user to perform a metagenomic analysis of marker genes with QIMME2 and a metatranscriptomic study using Kraken2/Bracken. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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13 pages, 1583 KiB  
Article
Gut Microbiome and Mycobiome Alterations in an In Vivo Model of Alzheimer’s Disease
by Valeria D’Argenio, Iolanda Veneruso, Chunmei Gong, Valentina Cecarini, Laura Bonfili and Anna Maria Eleuteri
Genes 2022, 13(9), 1564; https://doi.org/10.3390/genes13091564 - 31 Aug 2022
Cited by 14 | Viewed by 2643
Abstract
Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer’s disease (AD), suggesting possible [...] Read more.
Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer’s disease (AD), suggesting possible pathogenetic mechanisms contributing to the development of specific AD hallmarks and exacerbating metabolic alterations and neuroinflammation. The identification of these mechanisms is crucial to develop novel, targeted therapies and identify potential biomarkers for diagnostic purposes. Thus, the possibility to have AD in vivo models to study this microbial ecosystem represents a great opportunity for translational applications. Here, we characterized both gut microbiome and mycobiome of 3xTg-AD mice, one of the most widely used AD models, to identify specific microbial alterations with respect to the wild-type counterpart. Interestingly, we found a significant reduction of the Coprococcus and an increased abundance of Escherichia_Shigella and Barnesiella genera in the AD mice compatible with a pro-inflammatory status and the development of AD-related pathogenetic features. Moreover, the fungal Dipodascaceae family was significantly increased, thus suggesting a possible contribution to the metabolic alterations found in AD. Our data point out the strict connection between bacterial dysbiosis and AD and, even if further studies are required to clarify the underlining mechanisms, it clearly indicates the need for extensive metagenomic studies over the bacterial counterpart. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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Review

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17 pages, 990 KiB  
Review
Exploring the Diet-Gut Microbiota-Epigenetics Crosstalk Relevant to Neonatal Diabetes
by Naser A. Alsharairi
Genes 2023, 14(5), 1017; https://doi.org/10.3390/genes14051017 - 29 Apr 2023
Cited by 4 | Viewed by 2434
Abstract
Neonatal diabetes (NDM) is a rare monogenic disorder that presents as hyperglycemia during the first six months of life. The link between early-life gut microbiota dysbiosis and susceptibility to NDM remains uncertain. Experimental studies have demonstrated that gestational diabetes mellitus (GDM) could develop [...] Read more.
Neonatal diabetes (NDM) is a rare monogenic disorder that presents as hyperglycemia during the first six months of life. The link between early-life gut microbiota dysbiosis and susceptibility to NDM remains uncertain. Experimental studies have demonstrated that gestational diabetes mellitus (GDM) could develop into meconium/gut microbiota dysbiosis in newborns, and thus, it is thought to be a mediator in the pathogenesis of NDM. Epigenetic modifications have been considered as potential mechanisms by which the gut microbiota and susceptibility genes interact with the neonatal immune system. Several epigenome-wide association studies have revealed that GDM is associated with neonatal cord blood and/or placental DNA methylation alterations. However, the mechanisms linking diet in GDM with gut microbiota alterations, which may in turn induce the expression of genes linked to NDM, are yet to be unraveled. Therefore, the focus of this review is to highlight the impacts of diet, gut microbiota, and epigenetic crosstalk on altered gene expression in NDM. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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13 pages, 928 KiB  
Review
Human Genes Involved in the Interaction between Host and Gut Microbiome: Regulation and Pathogenic Mechanisms
by Luigi Boccuto, Jan Tack, Gianluca Ianiro, Ludovico Abenavoli and Emidio Scarpellini
Genes 2023, 14(4), 857; https://doi.org/10.3390/genes14040857 - 31 Mar 2023
Cited by 4 | Viewed by 2544
Abstract
Introduction: The umbrella term “human gut microbiota” describes the complex ecosystem harboring our gut. It includes bacteria, viruses, protozoa, archaea, fungi, and yeasts. This taxonomic classification does not describe its functions, which encompass nutrients digestion and absorption, immune system regulation, and host metabolism. [...] Read more.
Introduction: The umbrella term “human gut microbiota” describes the complex ecosystem harboring our gut. It includes bacteria, viruses, protozoa, archaea, fungi, and yeasts. This taxonomic classification does not describe its functions, which encompass nutrients digestion and absorption, immune system regulation, and host metabolism. “Gut microbiome” indicates instead the genome belonging to these “microbes” actively involved in these functions. However, the interaction between the host genome and the microbial ones determines the fine functioning of our organism. Methods: We reviewed the data available in the scientific literature on the definition of gut microbiota, gut microbiome, and the data on human genes involved in the interaction with the latter. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, gut microbiome, human genes, immune function, and metabolism. Results: Candidate human genes encoding enzymes, inflammatory cytokines, and proteins show similarity with those included in the gut microbiome. These findings have become available through newer artificial intelligence (AI) algorithms allowing big data analysis. From an evolutionary point of view, these pieces of evidence explain the strict and sophisticated interaction at the basis of human metabolism and immunity regulation in humans. They unravel more and more physiopathologic pathways included in human health and disease. Discussion: Several lines of evidence also obtained through big data analysis support the bi-directional role of gut microbiome and human genome in host metabolism and immune system regulation. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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14 pages, 1202 KiB  
Review
Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases
by Yoshimitsu Kiriyama and Hiromi Nochi
Genes 2023, 14(4), 825; https://doi.org/10.3390/genes14040825 - 29 Mar 2023
Cited by 4 | Viewed by 1820
Abstract
Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety [...] Read more.
Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety of ways by different types of bacteria present in the gut microbiota, changes in the gut microbiota can affect the metabolism of BAs in the host. Although most BAs absorbed from the gut are transferred to the liver, some are transferred to the systemic circulation. Furthermore, BAs have also been detected in the brain and are thought to migrate into the brain through the systemic circulation. Although BAs are known to affect a variety of physiological functions by acting as ligands for various nuclear and cell-surface receptors, BAs have also been found to act on mitochondria and autophagy in the cell. This review focuses on the BAs modified by the gut microbiota and their roles in intracellular organelles and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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13 pages, 1060 KiB  
Review
The Yin-Yang Pharmacomicrobiomics on Treatment Response in Inflammatory Arthritides: A Narrative Review
by Silvia Peretti, Sara Torracchi, Edda Russo, Francesco Bonomi, Elisa Fiorentini, Khadija El Aoufy, Cosimo Bruni, Gemma Lepri, Martina Orlandi, Maria Sole Chimenti, Serena Guiducci, Amedeo Amedei, Marco Matucci-Cerinic and Silvia Bellando Randone
Genes 2023, 14(1), 89; https://doi.org/10.3390/genes14010089 - 28 Dec 2022
Cited by 2 | Viewed by 2039
Abstract
(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions [...] Read more.
(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions that are studied by the growing field of pharmacomicrobiomics. The aim of this review is to highlight current evidence on pharmacomicrobiomics applied to the main treatments of Rheumatoid Arthritis and Spondyloarthritis in order to maximize therapeutic success, in the framework of Personalized Medicine. (2) Methods: We performed a narrative review concerning pharmacomicrobiomics in inflammatory arthritides. We evaluated the influence of gut microbiota on treatment response of conventional Disease Modifying Anti-Rheumatic drugs (cDMARDs) (Methotrexate and Leflunomide) and biological Disease Modifying Anti-Rheumatic drugs (bDMARDs) (Tumor necrosis factor inhibitors, Interleukin-17 inhibitors, Interleukin 12/23 inhibitors, Abatacept, Janus Kinase inhibitors and Rituximab). (3) Results: We found a great amount of studies concerning Methotrexate and Tumor Necrosis Inhibitors (TNFi). Conversely, fewer data were available about Interleukin-17 inhibitors (IL-17i) and Interleukin 12/23 inhibitors (IL-12/23i), while none was identified for Janus Kinase Inhibitors (JAKi), Tocilizumab, Abatacept and Rituximab. We observed that microbiota and drugs are influenced in a mutual and reciprocal way. Indeed, microbiota seems to influence therapeutic response and efficacy, whereas in the other hand, drugs may restore healthy microbiota. (4) Conclusions: Future improvement in pharmacomicrobiomics could help to detect an effective biomarker able to guide treatment choice and optimize management of inflammatory arthritides. Full article
(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)
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