Molecular and Translational Research of the Microbiome in Infectious and Non-infectious Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 29578

Special Issue Editor


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Guest Editor
Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA
Interests: microbiome; disease prevention; systems biology; nutraceuticals (prebiotic and probiotics); immune protection; developmental programming; anti-aging/healthspan; food and drug toxicity
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Special Issue Information

Dear Colleagues,

The human microbiome provides the vast majority of genes, significant metabolic capacity, and exquisite physiological regulation of the human holobiont. As such, it is the starting point for determining risk of both infectious and non-infectious disease (NCDs). This special issue welcomes both original research and review articles and is divided into two interlinked parts. The first part involves research into the molecular pathways that determine microbiome dysbiosis and/or those that connect the dysbiosis with systems biology dysfunction. The second part deals with translation of microbiome-host systems interactions that lead us toward effective disease prevention and/or cures of infectious or noninfectious diseases (e.g., NCDs.)

Prof. Dr. Rodney R. Dietert
Guest Editor

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Keywords

  • microbiome
  • metabolomics
  • molecular pathways
  • biomedicines
  • systems biology
  • infectious diseases
  • noncommunicable diseases
  • disease prevention and treatment

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Published Papers (8 papers)

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Research

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12 pages, 1235 KiB  
Article
Fecal Microbiota Transplantation in Patients Co-Infected with SARS-CoV2 and Clostridioides difficile
by Adrian Boicean, Bogdan Neamtu, Sabrina Birsan, Florina Batar, Ciprian Tanasescu, Horatiu Dura, Mihai Dan Roman, Adrian Hașegan, Dan Bratu, Alin Mihetiu, Călin Ilie Mohor, Cosmin Mohor, Ciprian Bacila, Mihai Octavian Negrea and Sorin Radu Fleaca
Biomedicines 2023, 11(1), 7; https://doi.org/10.3390/biomedicines11010007 - 21 Dec 2022
Cited by 19 | Viewed by 2705
Abstract
Background: The COVID-19 pandemic has challenged the treatment of Clostridioides Difficile (CD)-infected patients given the increasing number of co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, fecal microbiota transplantation (FMT) shows promise in modulating the immune system’s function and alleviating [...] Read more.
Background: The COVID-19 pandemic has challenged the treatment of Clostridioides Difficile (CD)-infected patients given the increasing number of co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, fecal microbiota transplantation (FMT) shows promise in modulating the immune system’s function and alleviating the burdens associated with this condition. Methods: To achieve this goal, we performed a comparative, retrospective, single-center study on 86 patients (admitted between January 2020 and March 2022). We based our approach on specific inclusion criteria: 1. The study group included 46 co-infected patients (COVID-19 and CD) receiving antibiotics and FMT; 2. In the control group, 40 co-infected patients received antibiotics only. Our results showed no significant group differences in terms of gender, age, risk factors such as cardiovascular and neurological diseases, type 2 diabetes, and obesity (p > 0.05), or in pre-treatment inflammatory status, evaluated by white blood cell (WBC) count and C-reactive protein (CRP) levels. We report a significant decrease in inflammatory syndrome (CRP, WBC) in coinfected patients receiving FMT in addition to antibiotics (p < 0.05), with a lower relapse rate and mitigation of cramping and abdominal pain (91.3%). In addition, a higher level of fibrinogen, persistent moderate abdominal pain (82.5%), and a significantly higher CD infection relapse rate (42.5%) were recorded in co-infected patients treated only with antibiotics (p < 0.05). Conclusion: Our study provides new data to support the multiple benefits of FMT in the case of COVID-19 and CD co-infection by improving patients’ quality of life and inflammatory syndrome. Full article
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15 pages, 4624 KiB  
Article
Impact of COVID-19 and Antibiotic Treatments on Gut Microbiome: A Role for Enterococcus spp.
by Elda Righi, Lorenza Lambertenghi, Anna Gorska, Concetta Sciammarella, Federico Ivaldi, Massimo Mirandola, Assunta Sartor and Evelina Tacconelli
Biomedicines 2022, 10(11), 2786; https://doi.org/10.3390/biomedicines10112786 - 2 Nov 2022
Cited by 10 | Viewed by 2180
Abstract
Objective: Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified. Design: The prospective cohort study included hospitalized COVID-19 patients [...] Read more.
Objective: Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified. Design: The prospective cohort study included hospitalized COVID-19 patients (April–December 2020). The gut microbiome composition was analysed by 16S sequencing. The gut diversity and changes in opportunistic bacteria (OBs) or symbionts were analysed according to clinical parameters, laboratory markers of disease progression, type of non-antibiotic COVID-19 treatments (NACT) and type, WHO AWaRe group, and duration of antibiotic therapy (AT). Results: A total of 82 patients (mean age 66 ± 13 years, 70% males) were enrolled. The relative abundance of Enterococcus was significantly correlated with duration of hospitalization, intensive care unit stay, O2 needs, and D-dimer, ferritin, and IL-6 blood levels. The presence of Enterococcus showed the highest number of correlations with NACT, AT, and AT + NACT (e.g., hydroxychloroquine ± lopinavir/ritonavir) and increased relative abundance with AWaRe Watch/Reserve antibiotics, AT duration, and combinations. Abundance of Dorea, Agathobacter, Roseburia, and Barnesiella was negatively correlated with AT and corticosteroids use. Patients with increased IL-6, D-dimer, and ferritin levels receiving AT were more likely to show dysbiosis with increased abundance of Enterococcus and Bilophila bacteria and decreased abundance of Roseburia compared with those not receiving AT. Conclusion: Microbiome diversity is affected by COVID-19 severity. In this context, antibiotic treatment may shift the gut microbiome composition towards OBs, particularly Enterococcus. The impact of treatment-driven dysbiosis on OBs infections and long-term consequences needs further study to define the role of gut homeostasis in COVID-19 recovery and inform targeted interventions. Full article
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17 pages, 8168 KiB  
Article
Characterization of the Urinary Metagenome and Virome in Healthy Children
by Eman Wehedy, Selvasankar Murugesan, Chinnu Reeba George, Ibrahim F. Shatat and Souhaila Al Khodor
Biomedicines 2022, 10(10), 2412; https://doi.org/10.3390/biomedicines10102412 - 27 Sep 2022
Cited by 6 | Viewed by 2255
Abstract
Recent advances in next-generation sequencing and metagenomic studies have provided insights into the microbial profile of different body sites. However, research on the microbial composition of urine is limited, particularly in children. The goal of this study was to optimize and develop reproducible [...] Read more.
Recent advances in next-generation sequencing and metagenomic studies have provided insights into the microbial profile of different body sites. However, research on the microbial composition of urine is limited, particularly in children. The goal of this study was to optimize and develop reproducible metagenome and virome protocols using a small volume of urine samples collected from healthy children. We collected midstream urine specimens from 40 healthy children. Using the metagenomics shotgun approach, we tested various protocols. Different microbial roots such as Archaea, Bacteria, Eukaryota, and Viruses were successfully identified using our optimized urine protocol. Our data reflected much variation in the microbial fingerprints of children. Girls had significantly higher levels of Firmicutes, whereas boys had significantly higher levels of Actinobacteria. The genus Anaerococcus dominated the urinary bacteriome of healthy girls, with a significant increase in Anaerococcus prevotii, Anaerococcus vaginalis, and Veillonella parvula (p-value < 0.001) when compared with that of boys. An increased relative abundance of Xylanimonas and Arthrobacter, with a significantly high abundance of Arthrobacter sp. FB24 (p-value 0.0028) and Arthrobacter aurescences (p-value 0.015), was observed in boys. The urinary mycobiome showed a significant rise in the genus Malassezia and Malassezia globose fungus (p-value 0.009) in girls, whereas genus Saccharomyces (p-value 0.009) was significantly high in boys. The beta diversity of the urinary mycobiome was found to differ between different age groups. Boys had significantly more Mastadenovirus and Human mastadenovirus-A in their urinary virome than girls. With increasing age, we noticed an increase in the relative abundance of the order Caudovirales. Our optimized protocols allowed us to identify the unique microbes for each sex by using an adequate volume of urine (3–10 mL) to screen for the bacteriome, mycobiome, and virome profiles in the urine of healthy children. To the best of our knowledge, this is the first study to characterize the metagenomics profiles of urine in a healthy pediatric population. Full article
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13 pages, 1318 KiB  
Article
Efficacy of Selected Live Biotherapeutic Candidates to Inhibit the Interaction of an Adhesive-Invasive Escherichia coli Strain with Caco-2, HT29-MTX Cells and Their Co-Culture
by Bronwyn Smit, Chiemeka C. Chinaka, Albert A. Scott, Kirsten Gaiduschek, Eva Hatje, Anna Kuballa, Samantha Coulson, Wayne Finlayson and Mohammad Katouli
Biomedicines 2022, 10(9), 2245; https://doi.org/10.3390/biomedicines10092245 - 9 Sep 2022
Cited by 5 | Viewed by 2192
Abstract
Adherent-invasive Escherichia coli (AIEC) has been implicated as a microbiological factor in the pathogenesis of inflammatory bowel disease (IBD). We evaluated the ability of six live biotherapeutic products (LBPs) to inhibit the interaction of an AIEC strain to three cell lines representing human [...] Read more.
Adherent-invasive Escherichia coli (AIEC) has been implicated as a microbiological factor in the pathogenesis of inflammatory bowel disease (IBD). We evaluated the ability of six live biotherapeutic products (LBPs) to inhibit the interaction of an AIEC strain to three cell lines representing human gut epithelium. Co-inoculation of LBPs with AIEC showed a reduction in adhesion (up to 73%) and invasion of AIEC (up to 89%). Pre-inoculation of LBPs in HT-29-MTX and Caco-2 cells before challenging with AIEC further reduced the adhesion and invasion of the AIEC, with three LBPs showing significantly (p < 0.0001) higher efficiency in reducing the adhesion of AIEC. In co-inoculation experiments, the highest reduction in adhesion (73%) of AIEC was observed in HT-29-MTX cells, whereas the highest reduction in invasion (89%) was seen in HT-29-MTX and the co-culture of cells. Pre-inoculation of LBPs further reduced the invasion of AIEC with highest reduction (97%) observed in co-culture of cells. Our results indicated that whilst there were differences in the efficacy of LBPs, they all reduced interaction of AIEC with cell lines representing gut epithelium. Their efficiency was higher when they were pre-inoculated onto the cells, suggesting their potential as candidates for alleviating pathogenesis of AIEC in patients with IBD. Full article
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Review

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18 pages, 379 KiB  
Review
The Gut Microbiome and Its Implication in the Mucosal Digestive Disorders
by Laura Bozomitu, Ingrith Miron, Anca Adam Raileanu, Ancuta Lupu, Gabriela Paduraru, Florin Mihai Marcu, Ana Maria Laura Buga, Daniela Carmen Rusu, Felicia Dragan and Vasile Valeriu Lupu
Biomedicines 2022, 10(12), 3117; https://doi.org/10.3390/biomedicines10123117 - 2 Dec 2022
Cited by 23 | Viewed by 3591
Abstract
The gastrointestinal (GI) tract is one of the most studied compartments of the human body as it hosts the largest microbial community including trillions of germs. The relationship between the human and its associated flora is complex, as the microbiome plays an important [...] Read more.
The gastrointestinal (GI) tract is one of the most studied compartments of the human body as it hosts the largest microbial community including trillions of germs. The relationship between the human and its associated flora is complex, as the microbiome plays an important role in nutrition, metabolism and immune function. With a dynamic composition, influenced by many intrinsic and extrinsic factors, there is an equilibrium maintained in the composition of GI microbiota, translated as “eubiosis”. Any disruption of the microbiota leads to the development of different local and systemic diseases. This article reviews the human GI microbiome’s composition and function in healthy individuals as well as its involvement in the pathogenesis of different digestive disorders. It also highlights the possibility to consider flora manipulation a therapeutic option when treating GI diseases. Full article
16 pages, 314 KiB  
Review
Pain and Opioid-Induced Gut Microbial Dysbiosis
by Karen R. Thomas, Jacob Watt, Chuen Mong J. Wu, Adejoke Akinrinoye, Sairah Amjad, Lucy Colvin, Rachel Cowe, Sylvia H. Duncan, Wendy R. Russell and Patrice Forget
Biomedicines 2022, 10(8), 1815; https://doi.org/10.3390/biomedicines10081815 - 28 Jul 2022
Cited by 13 | Viewed by 4937
Abstract
Opioid-induced dysbiosis (OID) is a specific condition describing the consequences of opioid use on the bacterial composition of the gut. Opioids have been shown to affect the epithelial barrier in the gut and modulate inflammatory pathways, possibly mediating opioid tolerance or opioid-induced hyperalgesia; [...] Read more.
Opioid-induced dysbiosis (OID) is a specific condition describing the consequences of opioid use on the bacterial composition of the gut. Opioids have been shown to affect the epithelial barrier in the gut and modulate inflammatory pathways, possibly mediating opioid tolerance or opioid-induced hyperalgesia; in combination, these allow the invasion and proliferation of non-native bacterial colonies. There is also evidence that the gut-brain axis is linked to the emotional and cognitive aspects of the brain with intestinal function, which can be a factor that affects mental health. For example, Mycobacterium, Escherichia coli and Clostridium difficile are linked to Irritable Bowel Disease; Lactobacillaceae and Enterococcacae have associations with Parkinson’s disease, and Alistipes has increased prevalence in depression. However, changes to the gut microbiome can be therapeutically influenced with treatments such as faecal microbiota transplantation, targeted antibiotic therapy and probiotics. There is also evidence of emerging therapies to combat OID. This review has collated evidence that shows that there are correlations between OID and depression, Parkinson’s Disease, infection, and more. Specifically, in pain management, targeting OID deserves specific investigations. Full article
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22 pages, 1962 KiB  
Review
Oral Microbiome: Getting to Know and Befriend Neighbors, a Biological Approach
by Cecilia Bacali, Romana Vulturar, Smaranda Buduru, Angela Cozma, Adriana Fodor, Adina Chiș, Ondine Lucaciu, Laura Damian and Mirela Liliana Moldovan
Biomedicines 2022, 10(3), 671; https://doi.org/10.3390/biomedicines10030671 - 14 Mar 2022
Cited by 33 | Viewed by 6167
Abstract
The oral microbiome, forming a biofilm that covers the oral structures, contains a high number of microorganisms. Biofilm formation starts from the salivary pellicle that allows bacterial adhesion–colonization–proliferation, co-aggregation and biofilm maturation in a complex microbial community. There is a constant bidirectional crosstalk [...] Read more.
The oral microbiome, forming a biofilm that covers the oral structures, contains a high number of microorganisms. Biofilm formation starts from the salivary pellicle that allows bacterial adhesion–colonization–proliferation, co-aggregation and biofilm maturation in a complex microbial community. There is a constant bidirectional crosstalk between human host and its oral microbiome. The paper presents the fundamentals regarding the oral microbiome and its relationship to modulator factors, oral and systemic health. The modern studies of oral microorganisms and relationships with the host benefits are based on genomics, transcriptomics, proteomics and metabolomics. Pharmaceuticals such as antimicrobials, prebiotics, probiotics, surface active or abrasive agents and plant-derived ingredients may influence the oral microbiome. Many studies found associations between oral dysbiosis and systemic disorders, including autoimmune diseases, cardiovascular, diabetes, cancers and neurodegenerative disorders. We outline the general and individual factors influencing the host–microbial balance and the possibility to use the analysis of the oral microbiome in prevention, diagnosis and treatment in personalized medicine. Future therapies should take in account the restoration of the normal symbiotic relation with the oral microbiome. Full article
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29 pages, 420 KiB  
Review
Microbiome First Approaches to Rescue Public Health and Reduce Human Suffering
by Rodney R. Dietert
Biomedicines 2021, 9(11), 1581; https://doi.org/10.3390/biomedicines9111581 - 30 Oct 2021
Cited by 8 | Viewed by 4653
Abstract
The is a sequential article to an initial review suggesting that Microbiome First medical approaches to human health and wellness could both aid the fight against noncommunicable diseases and conditions (NCDs) and help to usher in sustainable healthcare. This current review article specifically [...] Read more.
The is a sequential article to an initial review suggesting that Microbiome First medical approaches to human health and wellness could both aid the fight against noncommunicable diseases and conditions (NCDs) and help to usher in sustainable healthcare. This current review article specifically focuses on public health programs and initiatives and what has been termed by medical journals as a catastrophic record of recent failures. Included in the review is a discussion of the four priority behavioral modifications (food choices, cessation of two drugs of abuse, and exercise) advocated by the World Health Organization as the way to stop the ongoing NCD epidemic. The lack of public health focus on the majority of cells and genes in the human superorganism, the microbiome, is highlighted as is the “regulatory gap” failure to protect humans, particularly the young, from a series of mass population toxic exposures (e.g., asbestos, trichloroethylene, dioxin, polychlorinated biphenyls, triclosan, bisphenol A and other plasticizers, polyfluorinated compounds, herbicides, food emulsifiers, high fructose corn syrup, certain nanoparticles, endocrine disruptors, and obesogens). The combination of early life toxicity for the microbiome and connected human physiological systems (e.g., immune, neurological), plus a lack of attention to the importance of microbial rebiosis has facilitated rather than suppressed, the NCD epidemic. This review article concludes with a call to place the microbiome first and foremost in public health initiatives as a way to both rescue public health effectiveness and reduce the human suffering connected to comorbid NCDs. Full article
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