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Biomedicines
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Pharmacomicrobiomics in Non-communicable Disease
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Pharmacomicrobiomics in Non-communicable Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 36179

Special Issue Editor

Dr. Amedeo Amedei

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Interests: microbiota-immunity axis; autoimmunity; cancers; inflammation; T cells; micro and nanoplastic effects on human
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmacomicrobiomics is a new branch that deals with investigating the interactions between the microbiome and the response to xenobiotics, defined as the effect of changes in the microbiome on drug action and toxicity. Noncommunicable diseases (NCDs), such as cardiovascular disease, cancer, respiratory disease and diabetes, are the result of a combination of genetic, physiological, environmental and behavioral factors.

Recent data have shown that one in four drugs that we routinely take to treat nonintestinal diseases alter the gut microbiome, causing adverse events, with an increase in bacterial resistance. In addition, it is well demonstrated that drug–microbial interactions occur mainly in the colon, where drugs may change the intestinal microenvironment, modify microbial metabolism and affect bacterial growth, by altering microbial community composition. This complexity means that pharmacological studies require a molecular biology approach studying cell signaling and the complex host–microbe–drug interactions.

Consequently, investigating the concept of pharmacomicrobiotics is important for understanding how the microbiota is involved in drug responses.

This new concept could pave the way for a new approach in which the intestinal microbiome represents the target to be modulated to increase the efficacy of drugs and reduce toxicity and adverse events.

Hence, the purpose of this Special Issue is to provide an overview of the relationship between pharmacomicrobiomics and NCDs in order to better understand the molecular mechanisms and how this new branch could lead to a new therapeutic approach.

Prof. Dr. Amedeo Amedei
Guest Editor

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Keywords

  • Microbiome
  • Cell signaling
  • Molecular pathway
  • Cancers
  • Chronic disorders
  • Heart disease
  • Inflammation
  • Immune response

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

4 pages, 187 KiB  
Editorial
Editorial of Special Issue “Pharmacomicrobiomics in Non-Communicable Disease”
by Amedeo Amedei
Biomedicines 2022, 10(7), 1605; https://doi.org/10.3390/biomedicines10071605 - 6 Jul 2022
Viewed by 1100
Abstract
The human superorganism, also known as the human holobiont, is a complex organism made up of host body as well as the bacteria, archaea, viruses, and fungi that live inside it along with their genes [...] Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)

Research

Jump to: Editorial, Review

16 pages, 3023 KiB  
Article
Bacterial-Specific Induction of Inflammatory Cytokines Significantly Decreases upon Dual Species Infections of Implant Materials with Periodontal Pathogens in a Mouse Model
by Muhammad Imran Rahim, Andreas Winkel, Alexandra Ingendoh-Tsakmakidis, Stefan Lienenklaus, Christine S. Falk, Michael Eisenburger and Meike Stiesch
Biomedicines 2022, 10(2), 286; https://doi.org/10.3390/biomedicines10020286 - 26 Jan 2022
Cited by 3 | Viewed by 3276
Abstract
Cytokine profiles are often perturbed after infections of medical implants. With a non-invasive in vivo imaging system, we report in a mouse model that interferon expression after infection of subcutaneous implants with Streptococcus oralis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema [...] Read more.
Cytokine profiles are often perturbed after infections of medical implants. With a non-invasive in vivo imaging system, we report in a mouse model that interferon expression after infection of subcutaneous implants with Streptococcus oralis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola (alone or as a combination) was species-specific, persisted longer in the presence of implants, and notably decreased upon dual species infections. This type I interferon expression disappeared within two weeks; however, histology of implant–tissue interface indicated high recruitment of immune cells even after three weeks. This was suggestive that biomaterial-associated infections could have prolonged effects, including the systemic stimulation of inflammatory cytokines. The present study investigated the systemic impact of this chronic peri-implant inflammation on the systemic expression of inflammatory cytokines (23) using a multiplex assay. Initially, the cytokine measurement in murine fibroblasts exposed to periodontal pathogens remained limited to the expression of five cytokines, namely, IL-6, G-CSF, CXCL-1/KC, MCP-1 (MCAF), and IL-12 (p40). The systemic determination of cytokines in mice increased to 19 cytokines (IL-1α, IL-2, IL-3, IL-5, IL-6, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-17A, CCL-11/Eotaxin, G-CSF, IFN-γ, CXCL1/KC, MCP-1 (MCAF), MIP-1α/CCL3, MIP-1β/CCL4, CCL5/RANTES, and TNF-α). Systemic induction of cytokines was species-specific in the mouse model. The cytokine induction from infected implants differed significantly from sole tissue infections and sterile implants. Notably, systemic cytokine induction decreased after infections with dual species compared to single species infections. These findings describe the systemic effect of chronic peri-implant inflammation on the systemic induction of inflammatory cytokines, and this effect was strongly correlated to the type and composition of initial infection. Systemic modulations in cytokine expression upon dual species infections exhibit an exciting pattern that might explain the complications associated with biomaterial-related infection in patients. Moreover, these findings validate the requirement of multispecies infections for pre-clinical studies involving animal models. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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Graphical abstract

11 pages, 2661 KiB  
Article
Probiotic Bifidobacterium bifidum G9-1 Has a Preventive Effect on the Acceleration of Colonic Permeability and M1 Macrophage Population in Maternally Separated Rats
by Xuan Wang, Hirokazu Fukui, Ying Ran, Xin Xu, Nobuhiko Ebisutani, Takashi Nakanishi, Yoshiki Tanaka, Ayako Maeda, Yutaka Makizaki, Toshihiko Tomita, Tadayuki Oshima and Hiroto Miwa
Biomedicines 2021, 9(6), 641; https://doi.org/10.3390/biomedicines9060641 - 3 Jun 2021
Cited by 9 | Viewed by 3449
Abstract
Although probiotics may be useful for the treatment of irritable bowel syndrome (IBS), it is unclear how probiotics play a role in colonic mucosal integrity and immunity. Here, we aimed to investigate the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on colonic mucosal integrity [...] Read more.
Although probiotics may be useful for the treatment of irritable bowel syndrome (IBS), it is unclear how probiotics play a role in colonic mucosal integrity and immunity. Here, we aimed to investigate the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on colonic mucosal integrity and macrophage behavior in rats subjected to maternal separation (MS) as a model of IBS. MS pups were individually separated from their mother rats, and a proportion of the MS rats were orally administered BBG9-1. The colonic mucosal permeability was evaluated by Ussing chamber assay. The expression of tight junction proteins and cytokines and the population of CD80-positive cells was examined in the colonic tissues by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Caco2 cells were stimulated with cytokines and the transepithelial electric resistance (TEER) was measured. MS rats showed significantly higher colonic permeability and lower claudin 4 expression in the colonic epithelium relative to controls. The number of CD80-positive macrophages was significantly increased in the colonic mucosa of MS rats, accompanied by the increase of IL-6 and IFN-γ expression. BBG9-1 treatment ameliorated the increase of M1 macrophage and IL-6/IFN-γ expression in the colonic tissue of MS rats. Simultaneously, BBG9-1 treatment improved the enhanced mucosal permeability and the decreased claudin 4 expression in the colon of MS rats. IL-6 and IFN-γ, whose expression is enhanced in the colon of MS rats, significantly decreased TEER in Caco2 cells in vitro. Probiotic BBG9-1 has a preventive effect on the acceleration of colonic permeability and M1 macrophage population in maternally separated rats. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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Review

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38 pages, 1386 KiB  
Review
Microbiome Modulation as a Therapeutic Approach in Chronic Skin Diseases
by Karina Polak, Antal Jobbágy, Tomasz Muszyński, Kamila Wojciechowska, Aleksandra Frątczak, András Bánvölgyi, Beata Bergler-Czop and Norbert Kiss
Biomedicines 2021, 9(10), 1436; https://doi.org/10.3390/biomedicines9101436 - 10 Oct 2021
Cited by 15 | Viewed by 4985
Abstract
There is a growing quantity of evidence on how skin and gut microbiome composition impacts the course of various dermatological diseases. The strategies involving the modulation of bacterial composition are increasingly in the focus of research attention. The aim of the present review [...] Read more.
There is a growing quantity of evidence on how skin and gut microbiome composition impacts the course of various dermatological diseases. The strategies involving the modulation of bacterial composition are increasingly in the focus of research attention. The aim of the present review was to analyze the literature available in PubMed (MEDLINE) and EMBASE databases on the topic of microbiome modulation in skin diseases. The effects and possible mechanisms of action of probiotics, prebiotics and synbiotics in dermatological conditions including atopic dermatitis (AD), psoriasis, chronic ulcers, seborrheic dermatitis, burns and acne were analyzed. Due to the very limited number of studies available regarding the topic of microbiome modulation in all skin diseases except for AD, the authors decided to also include case reports and original studies concerning oral administration and topical application of the pro-, pre- and synbiotics in the final analysis. The evaluated studies mostly reported significant health benefits to the patients or show promising results in animal or ex vivo studies. However, due to a limited amount of research and unambiguous results, the topic of microbiome modulation as a therapeutic approach in skin diseases still warrants further investigation. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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33 pages, 928 KiB  
Review
Biomarkers and Utility of the Antioxidant Potential of Probiotic Lactobacilli and Bifidobacteria as Representatives of the Human Gut Microbiota
by Olga V. Averina, Elena U. Poluektova, Mariya V. Marsova and Valery N. Danilenko
Biomedicines 2021, 9(10), 1340; https://doi.org/10.3390/biomedicines9101340 - 28 Sep 2021
Cited by 56 | Viewed by 5635
Abstract
Lactobacilli and bifidobacteria are an important part of human gut microbiota. Among numerous benefits, their antioxidant properties are attracting more and more attention. Multiple in vivo and in vitro studies have demonstrated that lactobacilli and bifidobacteria, along with their cellular components, possess excellent [...] Read more.
Lactobacilli and bifidobacteria are an important part of human gut microbiota. Among numerous benefits, their antioxidant properties are attracting more and more attention. Multiple in vivo and in vitro studies have demonstrated that lactobacilli and bifidobacteria, along with their cellular components, possess excellent antioxidant capacity, which provides a certain degree of protection to the human body against diseases associated with oxidative stress. Recently, lactobacilli and bifidobacteria have begun to be considered as a new source of natural antioxidants. This review summarizes the current state of research on various antioxidant properties of lactobacilli and bifidobacteria. Special emphasis is given to the mechanisms of antioxidant activity of these bacteria in the human gut microbiota, which involve bacterial cell components and metabolites. This review is also dedicated to the genes involved in the antioxidant properties of lactobacilli and bifidobacteria strains as indicators of their antioxidant potential in human gut microbiota. Identification of the antioxidant biomarkers of the gut microbiota is of great importance both for creating diagnostic systems for assessing oxidative stress and for choosing strategies aimed at restoring the normal functioning of the microbiota and, through it, restoring human health. In this review, the practical application of probiotic strains with proven antioxidant properties to prevent oxidative stress is also considered. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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13 pages, 916 KiB  
Review
Cardiovascular Diseases and Pharmacomicrobiomics: A Perspective on Possible Treatment Relevance
by Lavinia Curini and Amedeo Amedei
Biomedicines 2021, 9(10), 1338; https://doi.org/10.3390/biomedicines9101338 - 28 Sep 2021
Cited by 8 | Viewed by 2667
Abstract
Cardiovascular diseases (CVDs), the most common cause of mortality in rich countries, include a wide variety of pathologies of the heart muscle and vascular system that compromise the proper functioning of the heart. Most of the risk factors for cardiovascular diseases are well-known: [...] Read more.
Cardiovascular diseases (CVDs), the most common cause of mortality in rich countries, include a wide variety of pathologies of the heart muscle and vascular system that compromise the proper functioning of the heart. Most of the risk factors for cardiovascular diseases are well-known: lipid disorders, high serum LDL cholesterol, hypertension, smoking, obesity, diabetes, male sex and physical inactivity. Currently, much evidence shows that: (i) the human microbiota plays a crucial role in maintaining the organism’s healthy status; and (ii) a link exists between microbiota and cardiovascular function that, if dysregulated, could potentially correlate with CVDs. This scenario led the scientific community to carefully analyze the role of the microbiota in response to drugs, considering this the right path to improve the effectiveness of disease treatment. In this review, we examine heart diseases and highlight how the microbiota actually plays a preponderant role in their development. Finally, we investigate pharmacomicrobiomics—a new interesting field—and the microbiota’s role in modulating the response to drugs, to improve their effectiveness by making their action targeted, focusing particular attention on cardiovascular diseases and on innovative potential treatments. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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14 pages, 318 KiB  
Review
Microbiota and Myopericarditis: The New Frontier in the Car-Diological Field to Prevent or Treat Inflammatory Cardiomyo-Pathies in COVID-19 Outbreak
by Andrea Piccioni, Angela Saviano, Sara Cicchinelli, Laura Franza, Federico Rosa, Christian Zanza, Michele Cosimo Santoro, Marcello Candelli, Marcello Covino, Giulia Nannini, Amedeo Amedei and Francesco Franceschi
Biomedicines 2021, 9(9), 1234; https://doi.org/10.3390/biomedicines9091234 - 16 Sep 2021
Cited by 13 | Viewed by 3438
Abstract
Myopericarditis is an inflammatory heart condition involving the pericardium and myocardium. It can lead to heart failure, dilated cardiomyopathy, arrhythmia and sudden death. Its pathogenesis is mainly mediated by viral infections but also can be induced by bacterial infections, toxic substances and immune [...] Read more.
Myopericarditis is an inflammatory heart condition involving the pericardium and myocardium. It can lead to heart failure, dilated cardiomyopathy, arrhythmia and sudden death. Its pathogenesis is mainly mediated by viral infections but also can be induced by bacterial infections, toxic substances and immune mediated disorders. All these conditions can produce severe inflammation and myocardial injury, often associated with a poor prognosis. The specific roles of these different pathogens (in particular viruses), the interaction with the host, the interplay with gut microbiota, and the immune system responses to them are still not completely clear and under investigation. Interestingly, some research has demonstrated the contribution of the gut microbiota, and its related metabolites (some of which can mimic the cardiac myosin), in cardiac inflammation and in the progression of this disease. They can stimulate a continuous and inadequate immune response, with a subsequent myocardial inflammatory damage. The aim of our review is to investigate the role of gut microbiota in myopericarditis, especially for the cardiovascular implications of COVID-19 viral infection, based on the idea that the modulation of gut microbiota can be a new frontier in the cardiological field to prevent or treat inflammatory cardiomyopathies. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
25 pages, 1049 KiB  
Review
Microbiome First Medicine in Health and Safety
by Rodney R. Dietert
Biomedicines 2021, 9(9), 1099; https://doi.org/10.3390/biomedicines9091099 - 27 Aug 2021
Cited by 13 | Viewed by 6782
Abstract
Microbiome First Medicine is a suggested 21st century healthcare paradigm that prioritizes the entire human, the human superorganism, beginning with the microbiome. To date, much of medicine has protected and treated patients as if they were a single species. This has resulted in [...] Read more.
Microbiome First Medicine is a suggested 21st century healthcare paradigm that prioritizes the entire human, the human superorganism, beginning with the microbiome. To date, much of medicine has protected and treated patients as if they were a single species. This has resulted in unintended damage to the microbiome and an epidemic of chronic disorders [e.g., noncommunicable diseases and conditions (NCDs)]. Along with NCDs came loss of colonization resistance, increased susceptibility to infectious diseases, and increasing multimorbidity and polypharmacy over the life course. To move toward sustainable healthcare, the human microbiome needs to be front and center. This paper presents microbiome-human physiology from the view of systems biology regulation. It also details the ongoing NCD epidemic including the role of existing drugs and other factors that damage the human microbiome. Examples are provided for two entryway NCDs, asthma and obesity, regarding their extensive network of comorbid NCDs. Finally, the challenges of ensuring safety for the microbiome are detailed. Under Microbiome-First Medicine and considering the importance of keystone bacteria and critical windows of development, changes in even a few microbiota-prioritized medical decisions could make a significant difference in health across the life course. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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17 pages, 956 KiB  
Review
Impact of Environmental and Pharmacologic Changes on the Upper Gastrointestinal Microbiome
by Joshua Bilello and Ikenna Okereke
Biomedicines 2021, 9(6), 617; https://doi.org/10.3390/biomedicines9060617 - 29 May 2021
Cited by 9 | Viewed by 2735
Abstract
Diseases of the upper gastrointestinal tract have become more prevalent over time. Mechanisms of disease formation are still only partially understood. Recent literature has shown that the surrounding microbiome affects the propensity for disease formation in various parts of the upper gastrointestinal tract. [...] Read more.
Diseases of the upper gastrointestinal tract have become more prevalent over time. Mechanisms of disease formation are still only partially understood. Recent literature has shown that the surrounding microbiome affects the propensity for disease formation in various parts of the upper gastrointestinal tract. A review was performed of any literature to our best knowledge concerning the effects of pharmacologic agents, environmental changes, and surgical intervention on the microbiome of the upper gastrointestinal tract. Searches of the literature were performed using specific keywords related to drugs, surgical procedures, and environmental factors. Many prescription and nonprescription drugs that are commonly used have varying effects on the upper gastrointestinal tract. Proton pump inhibitors may affect the relative prevalence of some organisms in the lower esophagus and have less effect in the proximal esophagus. Changes in the esophageal microbiome correlate with some esophageal diseases. Drugs that induce weight loss have also been shown to affect the microbiomes of the esophagus and stomach. Common surgical procedures are associated with shifts in the microbial community in the gastrointestinal tract. Environmental factors have been shown to affect the microbiome in the upper gastrointestinal tract, as geographic differences correlate with alterations in the microbiome of the gastrointestinal tract. Understanding the association of environmental and pharmacologic changes on the microbiome of the upper gastrointestinal tract will facilitate treatment plans to reduce morbidity from disease. Full article
(This article belongs to the Special Issue Pharmacomicrobiomics in Non-communicable Disease)
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