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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 43818

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Dr. Maria Teresa Mascellino

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Department of Public Health and Infectious Diseases, Policlinico Umberto1 viale del Policlinico 155, Rome, Italy
Interests: bacterial antibiotic resistance; multidrug resistant microorganisms (MDR bacteria); probiotics; molecular laboratory methods; bacterial infections; biofilm and sonication; double carbapenem synergistic activity; association of antibiotics; enterobacterales; antimicrobial agents and resistance; relationship with the therapeutic approach; microbiota; Clostridium difficile infection; bacterial translocation and virulence factors; COVID 19 vaccines
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Dear Colleagues,

There are a variety of microorganisms in the human body, including fungi, bacteria and viruses, which account for about 1% to 3% of our body weight. They are usually harmless to the human body, and some can even protect our health by making vitamins, decomposing food and regulating immunity. These microorganisms form a large group called microbiome. More and more studies have shown that the changes of human microbiome are related to the occurrence of many diseases. For example alteration of the normal gut integrity is present during Clostridium difficile infections (CDI). In fact markers of microbial translocation, inflammation, and intestinal damage which are still present at clinical resolution of CDI, can be evaluated in patients with such disease. Improving microbiome may be applied to the treatment of diseases. Our microbiota plays a vital role in our health: it protects us against pathogens, promotes the development of our immune system, and helps metabolize various compounds. Maintaining a balanced microbial ecosystem is essential for defending our health. Several studies have shown significant changes in the balance of microorganisms in the host population or in the environment and this can be associated with significant changes in the balance of microorganisms in the host population. The goal of this special issue is to describe the human microbiome and analyse its role in human health and disease. In conclusion, this research topic is open in the broad subject area of microbiome and human health diseases. Welcome to submit a review of articles that study the human microbiome and analyse its role in human health and disease. The following are some recognized research cases, but not limited to the following:

single group or multi group analysis of gene expression in microbiome and cell line (or animal model)
microbiota analysis of patients with inflammatory bowel disease
analyse metabolites secreted by the microbiome and their effects on patients with neuropathic diseases
analyse specific pathogenic organisms, their carcinogenic potential and potential mechanisms
changes in microbial populations in some diseases
Clostridium difficile Infection

Dr. Maria Teresa Mascellino
Guest Editor

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Keywords

Microbiome
microbial population
inflammatory bowel disease
bacterial translocation
Clostridium difficile infection

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

4 pages, 756 KiB

Open AccessEditorial

Molecular Research in Human Microbiome

by Maria Teresa Mascellino

Int. J. Mol. Sci. 2023, 24(19), 14975; https://doi.org/10.3390/ijms241914975 - 7 Oct 2023

Viewed by 1404

Abstract

Recent evidence has shown that the human microbiome is associated with a wide range of diseases, from non-neoplastic to tumourigenesis, including cancer, inflammation, intestinal damage, etc [...] Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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Research

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17 pages, 3055 KiB

Open AccessArticle

Comparative Analysis of the Placental Microbiome in Pregnancies with Late Fetal Growth Restriction versus Physiological Pregnancies

by Aleksandra Stupak, Tomasz Gęca, Anna Kwaśniewska, Radosław Mlak, Paweł Piwowarczyk, Robert Nawrot, Anna Goździcka-Józefiak and Wojciech Kwaśniewski

Int. J. Mol. Sci. 2023, 24(8), 6922; https://doi.org/10.3390/ijms24086922 - 7 Apr 2023

Cited by 9 | Viewed by 2509

Abstract

A comparative analysis of the placental microbiome in pregnancies with late fetal growth restriction (FGR) was performed with normal pregnancies to assess the impact of bacteria on placental development and function. The presence of microorganisms in the placenta, amniotic fluid, fetal membranes and umbilical cord blood throughout pregnancy disproves the theory of the “sterile uterus”. FGR occurs when the fetus is unable to follow a biophysically determined growth path. Bacterial infections have been linked to maternal overproduction of pro-inflammatory cytokines, as well as various short- and long-term problems. Proteomics and bioinformatics studies of placental biomass allowed the development of new diagnostic options. In this study, the microbiome of normal and FGR placentas was analyzed by LC-ESI-MS/MS mass spectrometry, and the bacteria present in both placentas were identified by analysis of a set of bacterial proteins. Thirty-six pregnant Caucasian women participated in the study, including 18 women with normal pregnancy and eutrophic fetuses (EFW > 10th percentile) and 18 women with late FGR diagnosed after 32 weeks of gestation. Based on the analysis of the proteinogram, 166 bacterial proteins were detected in the material taken from the placentas in the study group. Of these, 21 proteins had an exponentially modified protein abundance index (emPAI) value of 0 and were not included in further analysis. Of the remaining 145 proteins, 52 were also present in the material from the control group. The remaining 93 proteins were present only in the material collected from the study group. Based on the proteinogram analysis, 732 bacterial proteins were detected in the material taken from the control group. Of these, 104 proteins had an emPAI value of 0 and were not included in further analysis. Of the remaining 628 proteins, 52 were also present in the material from the study group. The remaining 576 proteins were present only in the material taken from the control group. In both groups, we considered the result of ns prot ≥ 60 as the cut-off value for the agreement of the detected protein with its theoretical counterpart. Our study found significantly higher emPAI values of proteins representative of the following bacteria: Actinopolyspora erythraea, Listeria costaricensis, E. coli, Methylobacterium, Acidobacteria bacterium, Bacteroidetes bacterium, Paenisporsarcina sp., Thiodiazotropha endol oripes and Clostridiales bacterium. On the other hand, in the control group statistically more frequently, based on proteomic data, the following were found: Flavobacterial bacterium, Aureimonas sp. and Bacillus cereus. Our study showed that placental dysbiosis may be an important factor in the etiology of FGR. The presence of numerous bacterial proteins present in the control material may indicate their protective role, while the presence of bacterial proteins detected only in the material taken from the placentas of the study group may indicate their potentially pathogenic nature. This phenomenon is probably important in the development of the immune system in early life, and the placental microbiota and its metabolites may have great potential in the screening, prevention, diagnosis and treatment of FGR. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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19 pages, 2423 KiB

Open AccessArticle

Analysis of 16S rRNA Gene Sequence of Nasopharyngeal Exudate Reveals Changes in Key Microbial Communities Associated with Aging

by Sergio Candel, Sylwia D. Tyrkalska, Fernando Pérez-Sanz, Antonio Moreno-Docón, Ángel Esteban, María L. Cayuela and Victoriano Mulero

Int. J. Mol. Sci. 2023, 24(4), 4127; https://doi.org/10.3390/ijms24044127 - 18 Feb 2023

Cited by 3 | Viewed by 2664

Abstract

Functional or compositional perturbations of the microbiome can occur at different sites, of the body and this dysbiosis has been linked to various diseases. Changes in the nasopharyngeal microbiome are associated to patient’s susceptibility to multiple viral infections, supporting the idea that the nasopharynx may be playing an important role in health and disease. Most studies on the nasopharyngeal microbiome have focused on a specific period in the lifespan, such as infancy or the old age, or have other limitations such as low sample size. Therefore, detailed studies analyzing the age- and sex-associated changes in the nasopharyngeal microbiome of healthy people across their whole life are essential to understand the relevance of the nasopharynx in the pathogenesis of multiple diseases, particularly viral infections. One hundred twenty nasopharyngeal samples from healthy subjects of all ages and both sexes were analyzed by 16S rRNA sequencing. Nasopharyngeal bacterial alpha diversity did not vary in any case between age or sex groups. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant phyla in all the age groups, with several sex-associated. Acinetobacter, Brevundimonas, Dolosigranulum, Finegoldia, Haemophilus, Leptotrichia, Moraxella, Peptoniphilus, Pseudomonas, Rothia, and Staphylococcus were the only 11 bacterial genera that presented significant age-associated differences. Other bacterial genera such as Anaerococcus, Burkholderia, Campylobacter, Delftia, Prevotella, Neisseria, Propionibacterium, Streptococcus, Ralstonia, Sphingomonas, and Corynebacterium appeared in the population with a very high frequency, suggesting that their presence might be biologically relevant. Therefore, in contrast to other anatomical areas such as the gut, bacterial diversity in the nasopharynx of healthy subjects remains stable and resistant to perturbations throughout the whole life and in both sexes. Age-associated abundance changes were observed at phylum, family, and genus levels, as well as several sex-associated changes probably due to the different levels of sex hormones present in both sexes at certain ages. Our results provide a complete and valuable dataset that will be useful for future research aiming for studying the relationship between changes in the nasopharyngeal microbiome and susceptibility to or severity of multiple diseases. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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23 pages, 5625 KiB

Open AccessArticle

Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association

by Barbara Kneis, Stefan Wirtz, Klaus Weber, Axel Denz, Matthias Gittler, Carol Geppert, Maximilian Brunner, Christian Krautz, Alexander Reinhard Siebenhüner, Robert Schierwagen, Olaf Tyc, Abbas Agaimy, Robert Grützmann, Jonel Trebicka, Stephan Kersting and Melanie Langheinrich

Int. J. Mol. Sci. 2023, 24(4), 3265; https://doi.org/10.3390/ijms24043265 - 7 Feb 2023

Cited by 13 | Viewed by 3540

Abstract

In the current era of precision oncology, it is widely acknowledged that CRC is a heterogeneous disease entity. Tumor location (right- or left-sided colon cancer or rectal cancer) is a crucial factor in determining disease progression as well as prognosis and influences disease management. In the last decade, numerous works have reported that the microbiome is an important element of CRC carcinogenesis, progression and therapy response. Owing to the heterogeneous nature of microbiomes, the findings of these studies were inconsistent. The majority of the studies combined colon cancer (CC) and rectal cancer (RC) samples as CRC for analysis. Furthermore, the small intestine, as the major site for immune surveillance in the gut, is understudied compared to the colon. Thus, the CRC heterogeneity puzzle is far from being solved, and more research is necessary for prospective trials that separately investigate CC and RC. Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing in biopsy samples from the terminal ileum, healthy colon tissue, healthy rectal tissue and tumor tissue as well as in preoperative and postoperative stool samples of 41 patients. While fecal samples provide a good approximation of the average gut microbiome composition, mucosal biopsies allow for detecting subtle variations in local microbial communities. In particular, the small bowel microbiome has remained poorly characterized, mainly because of sampling difficulties. Our analysis revealed the following: (i) right- and left-sided colon cancers harbor distinct and diverse microbiomes, (ii) the tumor microbiome leads to a more consistent cancer-defined microbiome between locations and reveals a tumor microbiome–ileal microbiome association, (iii) the stool only partly reflects the microbiome landscape in patients with CC, and (iv) mechanical bowel preparation and perioperative antibiotics together with surgery result in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as Enterococcus. Collectively, our results provide new and valuable insights into the complex microbiome landscape in patients with colon cancer. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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Review

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15 pages, 2406 KiB

Open AccessReview

Helicobacter pylori Antibiotic Resistance: Molecular Basis and Diagnostic Methods

by Irina Medakina, Larisa Tsapkova, Vera Polyakova, Sergey Nikolaev, Tatyana Yanova, Natalia Dekhnich, Igor Khatkov, Dmitry Bordin and Natalia Bodunova

Int. J. Mol. Sci. 2023, 24(11), 9433; https://doi.org/10.3390/ijms24119433 - 29 May 2023

Cited by 17 | Viewed by 4964

Abstract

Helicobacter pylori is one of the most common cause of human infections. Infected patients develop chronic active gastritis in all cases, which can lead to peptic ulcer, atrophic gastritis, gastric cancer and gastric MALT-lymphoma. The prevalence of H. pylori infection in the population has regional characteristics and can reach 80%. Constantly increasing antibiotic resistance of H. pylori is a major cause of treatment failure and a major problem. According to the VI Maastricht Consensus, two main strategies for choosing eradication therapy are recommended: individualized based on evaluating sensitivity to antibacterial drugs (phenotypic or molecular genetic method) prior to their appointment, and empirical, which takes into account data on local H. pylori resistance to clarithromycin and monitoring effectiveness schemes in the region. Therefore, the determination of H. pylori resistance to antibiotics, especially clarithromycin, prior to choosing therapeutic strategy is extremely important for the implementation of these treatment regimens. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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16 pages, 1169 KiB

Open AccessReview

Exploring the Involvement of Gut Microbiota in Cancer Therapy-Induced Cardiotoxicity

by Kunika, Norbert Frey and Ashraf Y. Rangrez

Int. J. Mol. Sci. 2023, 24(8), 7261; https://doi.org/10.3390/ijms24087261 - 14 Apr 2023

Cited by 8 | Viewed by 3500

Abstract

Trillions of microbes in the human intestinal tract, including bacteria, viruses, fungi, and protozoa, are collectively referred to as the gut microbiome. Recent technological developments have led to a significant increase in our understanding of the human microbiome. It has been discovered that the microbiome affects both health and the progression of diseases, including cancer and heart disease. Several studies have indicated that the gut microbiota may serve as a potential target in cancer therapy modulation, by enhancing the effectiveness of chemotherapy and/or immunotherapy. Moreover, altered microbiome composition has been linked to the long-term effects of cancer therapy; for example, the deleterious effects of chemotherapy on microbial diversity can, in turn, lead to acute dysbiosis and serious gastrointestinal toxicity. Specifically, the relationship between the microbiome and cardiac diseases in cancer patients following therapy is poorly understood. In this article, we provide a summary of the role of the microbiome in cancer treatment, while also speculating on a potential connection between treatment-related microbial changes and cardiotoxicity. Through a brief review of the literature, we further explore which bacterial families or genera were differentially affected in cancer treatment and cardiac disease. A deeper understanding of the link between the gut microbiome and cardiotoxicity caused by cancer treatment may help lower the risk of this critical and potentially fatal side effect. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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20 pages, 363 KiB

Open AccessReview

What the Gut Tells the Brain—Is There a Link between Microbiota and Huntington’s Disease?

by Dorota Wronka, Anna Karlik, Julia O. Misiorek and Lukasz Przybyl

Int. J. Mol. Sci. 2023, 24(5), 4477; https://doi.org/10.3390/ijms24054477 - 24 Feb 2023

Cited by 11 | Viewed by 3915

Abstract

The human intestinal microbiota is a diverse and dynamic microenvironment that forms a complex, bi-directional relationship with the host. The microbiome takes part in the digestion of food and the generation of crucial nutrients such as short chain fatty acids (SCFA), but is also impacts the host’s metabolism, immune system, and even brain functions. Due to its indispensable role, microbiota has been implicated in both the maintenance of health and the pathogenesis of many diseases. Dysbiosis in the gut microbiota has already been implicated in many neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). However, not much is known about the microbiome composition and its interactions in Huntington’s disease (HD). This dominantly heritable, incurable neurodegenerative disease is caused by the expansion of CAG trinucleotide repeats in the huntingtin gene (HTT). As a result, toxic RNA and mutant protein (mHTT), rich in polyglutamine (polyQ), accumulate particularly in the brain, leading to its impaired functions. Interestingly, recent studies indicated that mHTT is also widely expressed in the intestines and could possibly interact with the microbiota, affecting the progression of HD. Several studies have aimed so far to screen the microbiota composition in mouse models of HD and find out whether observed microbiome dysbiosis could affect the functions of the HD brain. This review summarizes ongoing research in the HD field and highlights the essential role of the intestine-brain axis in HD pathogenesis and progression. The review also puts a strong emphasis on indicating microbiome composition as a future target in the urgently needed therapy for this still incurable disease. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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12 pages, 1343 KiB

Open AccessReview

The Impact of Non-Pathogenic Bacteria on the Spread of Virulence and Resistance Genes

by Francisco Dionisio, Célia P. F. Domingues, João S. Rebelo, Francisca Monteiro and Teresa Nogueira

Int. J. Mol. Sci. 2023, 24(3), 1967; https://doi.org/10.3390/ijms24031967 - 19 Jan 2023

Cited by 11 | Viewed by 3747

Abstract

This review discusses the fate of antimicrobial resistance and virulence genes frequently present among microbiomes. A central concept in epidemiology is the mean number of hosts colonized by one infected host in a population of susceptible hosts: R₀. It characterizes the disease’s epidemic potential because the pathogen continues its propagation through susceptible hosts if it is above one. R₀ is proportional to the average duration of infections, but non-pathogenic microorganisms do not cause host death, and hosts do not need to be rid of them. Therefore, commensal bacteria may colonize hosts for prolonged periods, including those harboring drug resistance or even a few virulence genes. Thus, their R₀ is likely to be (much) greater than one, with peculiar consequences for the spread of virulence and resistance genes. For example, computer models that simulate the spread of these genes have shown that their diversities should correlate positively throughout microbiomes. Bioinformatics analysis with real data corroborates this expectation. Those simulations also anticipate that, contrary to the common wisdom, human’s microbiomes with a higher diversity of both gene types are the ones that took antibiotics longer ago rather than recently. Here, we discuss the mechanisms and robustness behind these predictions and other public health consequences. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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17 pages, 3831 KiB

Open AccessReview

Microbiome and Metabolomics in Liver Cancer: Scientific Technology

by Raja Ganesan, Sang Jun Yoon and Ki Tae Suk

Int. J. Mol. Sci. 2023, 24(1), 537; https://doi.org/10.3390/ijms24010537 - 28 Dec 2022

Cited by 17 | Viewed by 4349

Abstract

Primary liver cancer is a heterogeneous disease. Liver cancer metabolism includes both the reprogramming of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment and fluctuations in regular tissue metabolism. Currently, metabolomics and metabolite profiling in liver cirrhosis, liver cancer, and hepatocellular carcinoma (HCC) have been in the spotlight in terms of cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecules, chemicals, and metabolites. Metabolomics technologies can provide critical information about the liver cancer state. Here, we review how liver cirrhosis, liver cancer, and HCC therapies interact with metabolism at the cellular and systemic levels. An overview of liver metabolomics is provided, with a focus on currently available technologies and how they have been used in clinical and translational research. We also list scalable methods, including chemometrics, followed by pathway processing in liver cancer. We conclude that important drivers of metabolomics science and scientific technologies are novel therapeutic tools and liver cancer biomarker analysis. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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17 pages, 1132 KiB

Open AccessReview

The Connection between Gut and Lung Microbiota, Mast Cells, Platelets and SARS-CoV-2 in the Elderly Patient

by Giovanna Traina

Int. J. Mol. Sci. 2022, 23(23), 14898; https://doi.org/10.3390/ijms232314898 - 28 Nov 2022

Cited by 7 | Viewed by 1837

Abstract

The human coronavirus SARS-CoV-2 or COVID-19 that emerged in late 2019 causes a respiratory tract infection and has currently resulted in more than 627 million confirmed cases and over 6.58 million deaths worldwide up to October 2022. The highest death rate caused by COVID-19 is in older people, especially those with comorbidities. This evidence presents a challenge for biomedical research on aging and also identifies some key players in inflammation, including mast cells and platelets, which could represent important markers and, at the same time, unconventional therapeutic targets. Studies have shown a decrease in the diversity of gut microbiota composition in the elderly, particularly a reduced abundance of butyrate-producing species, and COVID-19 patients manifest faecal microbiome alterations, with an increase in opportunistic pathogens and a depletion of commensal beneficial microorganisms. The main purpose of this narrative review is to highlight how an altered condition of the gut microbiota, especially in the elderly, could be an important factor and have a strong impact in the lung homeostasis and COVID-19 phenomenon, jointly to the activation of mast cells and platelets, and also affect the outcomes of the pathology. Therefore, a targeted and careful control of the intestinal microbiota could represent a complementary intervention to be implemented for the management and the challenge against COVID-19. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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14 pages, 1171 KiB

Open AccessReview

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers

by Andrea Piccioni, Federico Rosa, Federica Manca, Giulia Pignataro, Christian Zanza, Gabriele Savioli, Marcello Covino, Veronica Ojetti, Antonio Gasbarrini, Francesco Franceschi and Marcello Candelli

Int. J. Mol. Sci. 2022, 23(21), 13323; https://doi.org/10.3390/ijms232113323 - 1 Nov 2022

Cited by 29 | Viewed by 3809

Abstract

Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual’s disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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18 pages, 1020 KiB

Open AccessReview

The Role of the Human Microbiome in the Pathogenesis of Pain

by Klaudia Ustianowska, Łukasz Ustianowski, Filip Machaj, Anna Gorący, Jakub Rosik, Bartosz Szostak, Joanna Szostak and Andrzej Pawlik

Int. J. Mol. Sci. 2022, 23(21), 13267; https://doi.org/10.3390/ijms232113267 - 31 Oct 2022

Cited by 27 | Viewed by 6403

Abstract

Understanding of the gut microbiome’s role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut–brain axis. The signals in the gut–brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut–brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut–brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome’s role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain. Full article

(This article belongs to the Special Issue Molecular Research in Human Microbiome)

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