International Journal of Molecular Sciences

Editorial

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4 pages, 194 KiB

Open AccessEditorial

Editorial of Special Issue “The Interplay of Microbiome and Immune Response in Health and Diseases—2nd Edition”

by Amedeo Amedei

Int. J. Mol. Sci. 2022, 23(13), 7169; https://doi.org/10.3390/ijms23137169 - 28 Jun 2022

Viewed by 1300

Abstract

The microbiota refers to the great number of microorganisms (including bacteria, fungi, viruses and parasites) that live on and in humans and has sparked a surge of recent interest [...] Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

5 pages, 191 KiB

Open AccessEditorial

Editorial of Special Issue “The Interplay of Microbiome and Immune Response in Health and Diseases”

by Amedeo Amedei and Gwendolyn Barceló-Coblijn

Int. J. Mol. Sci. 2019, 20(15), 3708; https://doi.org/10.3390/ijms20153708 - 29 Jul 2019

Cited by 6 | Viewed by 2769

Abstract

Increasing data suggests and supports the idea that the gut microbiota (GM) modulates different host pathways, playing a crucial role in human physiology and consequently impacting in the development of some pathologic conditions [...] Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

Research

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21 pages, 2850 KiB

Open AccessArticle

Early-Life Adversity Leaves Its Imprint on the Oral Microbiome for More Than 20 Years and Is Associated with Long-Term Immune Changes

by Eleftheria G. Charalambous, Sophie B. Mériaux, Pauline Guebels, Claude P. Muller, Fleur A. D. Leenen, Martha M. C. Elwenspoek, Ines Thiele, Johannes Hertel and Jonathan D. Turner

Int. J. Mol. Sci. 2021, 22(23), 12682; https://doi.org/10.3390/ijms222312682 - 24 Nov 2021

Cited by 16 | Viewed by 4256

Abstract

The early-life microbiome (ELM) interacts with the psychosocial environment, in particular during early-life adversity (ELA), defining life-long health trajectories. The ELM also plays a significant role in the maturation of the immune system. We hypothesised that, in this context, the resilience of the [...] Read more.

The early-life microbiome (ELM) interacts with the psychosocial environment, in particular during early-life adversity (ELA), defining life-long health trajectories. The ELM also plays a significant role in the maturation of the immune system. We hypothesised that, in this context, the resilience of the oral microbiomes, despite being composed of diverse and distinct communities, allows them to retain an imprint of the early environment. Using 16S amplicon sequencing on the EpiPath cohort, we demonstrate that ELA leaves an imprint on both the salivary and buccal oral microbiome 24 years after exposure to adversity. Furthermore, the changes in both communities were associated with increased activation, maturation, and senescence of both innate and adaptive immune cells, although the interaction was partly dependent on prior herpesviridae exposure and current smoking. Our data suggest the presence of multiple links between ELA, Immunosenescence, and cytotoxicity that occur through long-term changes in the microbiome. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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15 pages, 3358 KiB

Open AccessArticle

Microbial Co-Occurrence Patterns and Keystone Species in the Gut Microbial Community of Mice in Response to Stress and Chondroitin Sulfate Disaccharide

by Fang Liu, Zhaojie Li, Xiong Wang, Changhu Xue, Qingjuan Tang and Robert W. Li

Int. J. Mol. Sci. 2019, 20(9), 2130; https://doi.org/10.3390/ijms20092130 - 30 Apr 2019

Cited by 16 | Viewed by 4730

Abstract

Detecting microbial interactions is essential to the understanding of the structure and function of the gut microbiome. In this study, microbial co-occurrence patterns were inferred using a random matrix theory based approach in the gut microbiome of mice in response to chondroitin sulfate [...] Read more.

Detecting microbial interactions is essential to the understanding of the structure and function of the gut microbiome. In this study, microbial co-occurrence patterns were inferred using a random matrix theory based approach in the gut microbiome of mice in response to chondroitin sulfate disaccharide (CSD) under healthy and stressed conditions. The exercise stress disrupted the network composition and microbial co-occurrence patterns. Thirty-four Operational Taxonomic Units (OTU) were identified as module hubs and connectors, likely acting as generalists in the microbial community. Mucispirillum schaedleri acted as a connector in the stressed network in response to CSD supplement and may play a key role in bridging intimate interactions between the host and its microbiome. Several modules correlated with physiological parameters were detected. For example, Modules M02 (under stress) and S05 (stress + CSD) were strongly correlated with blood urea nitrogen levels (r = 0.90 and −0.75, respectively). A positive correlation between node connectivity of the OTUs assigned to Proteobacteria with superoxide dismutase activities under stress (r = 0.57, p < 0.05) provided further evidence that Proteobacteria can be developed as a potential pathological marker. Our findings provided novel insights into gut microbial interactions and may facilitate future endeavor in microbial community engineering. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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13 pages, 3569 KiB

Open AccessArticle

Intravenous Immunoglobulin Therapy Eliminates Candida albicans and Maintains Intestinal Homeostasis in a Murine Model of Dextran Sulfate Sodium-Induced Colitis

by Rogatien Charlet, Boualem Sendid, Srini V. Kaveri, Daniel Poulain, Jagadeesh Bayry and Samir Jawhara

Int. J. Mol. Sci. 2019, 20(6), 1473; https://doi.org/10.3390/ijms20061473 - 23 Mar 2019

Cited by 16 | Viewed by 4069

Abstract

Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy [...] Read more.

Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine interleukin (IL)-6 and enhancement of IL-10 in the gut. IVIg therapy also led to an increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), while toll-like receptor 4 (TLR-4) expression was reduced. IVIg treatment reduces intestinal inflammation in mice and eliminates C. albicans overgrowth from the gut in association with down-regulation of pro-inflammatory mediators combined with up-regulation of anti-inflammatory cytokines. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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14 pages, 4338 KiB

Open AccessArticle

A Small Aromatic Compound Has Antifungal Properties and Potential Anti-Inflammatory Effects against Intestinal Inflammation

by Clovis Bortolus, Muriel Billamboz, Rogatien Charlet, Karine Lecointe, Boualem Sendid, Alina Ghinet and Samir Jawhara

Int. J. Mol. Sci. 2019, 20(2), 321; https://doi.org/10.3390/ijms20020321 - 14 Jan 2019

Cited by 16 | Viewed by 3648

Abstract

Resistance of the opportunistic pathogen Candida albicans to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in [...] Read more.

Resistance of the opportunistic pathogen Candida albicans to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in vitro and in vivo against C. albicans overgrowth and intestinal inflammation. Substitution on the aromatic ring of DHMB led to a strong decrease in its biological activity against C. albicans. The MIC of DHMB was highly effective at eliminating C. albicans when compared to that of caspofungin or fluconazole. Additionally, DHMB was also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. DHMB was administered to animals at high doses. This compound was not cytotoxic and was well-tolerated. In experimental dextran sodium sulphate (DSS)-induced colitis in mice, DHMB reduced the clinical and histological score of inflammation and promoted the elimination of C. albicans from the gut. This finding was supported by a decrease in aerobic bacteria while anaerobic bacteria populations were re-established in mice treated with DHMB. DHMB is a small organic molecule with antifungal properties and anti-inflammatory activity by exerting protective effects on intestinal epithelial cells. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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11 pages, 2580 KiB

Open AccessArticle

Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept

by Andrea Picchianti-Diamanti, Concetta Panebianco, Simonetta Salemi, Maria Laura Sorgi, Roberta Di Rosa, Alessandro Tropea, Mayla Sgrulletti, Gerardo Salerno, Fulvia Terracciano, Raffaele D’Amelio, Bruno Laganà and Valerio Pazienza

Int. J. Mol. Sci. 2018, 19(10), 2938; https://doi.org/10.3390/ijms19102938 - 27 Sep 2018

Cited by 147 | Viewed by 8019

Abstract

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction [...] Read more.

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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Review

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14 pages, 747 KiB

Open AccessReview

Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases

by Ting-Wei Kao and Chin-Chou Huang

Int. J. Mol. Sci. 2022, 23(2), 804; https://doi.org/10.3390/ijms23020804 - 12 Jan 2022

Cited by 8 | Viewed by 4328

Abstract

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis [...] Read more.

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1β and −6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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16 pages, 2119 KiB

Open AccessReview

Gut Microbiota Extracellular Vesicles as Signaling Molecules Mediating Host-Microbiota Communications

by Salma Sultan, Walid Mottawea, JuDong Yeo and Riadh Hammami

Int. J. Mol. Sci. 2021, 22(23), 13166; https://doi.org/10.3390/ijms222313166 - 6 Dec 2021

Cited by 20 | Viewed by 12803

Abstract

Over the past decade, gut microbiota dysbiosis has been linked to many health disorders; however, the detailed mechanism of this correlation remains unclear. Gut microbiota can communicate with the host through immunological or metabolic signalling. Recently, microbiota-released extracellular vesicles (MEVs) have emerged as [...] Read more.

Over the past decade, gut microbiota dysbiosis has been linked to many health disorders; however, the detailed mechanism of this correlation remains unclear. Gut microbiota can communicate with the host through immunological or metabolic signalling. Recently, microbiota-released extracellular vesicles (MEVs) have emerged as significant mediators in the intercellular signalling mechanism that could be an integral part of microbiota-host communications. MEVs are small membrane-bound vesicles that encase a broad spectrum of biologically active compounds (i.e., proteins, mRNA, miRNA, DNA, carbohydrates, and lipids), thus mediating the horizontal transfer of their cargo across intra- and intercellular space. In this study, we provide a comprehensive and in-depth discussion of the biogenesis of microbial-derived EVs, their classification and routes of production, as well as their role in inter-bacterial and inter-kingdom signaling. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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26 pages, 1453 KiB

Open AccessReview

A Journey on the Skin Microbiome: Pitfalls and Opportunities

by Dario Pistone, Gabriele Meroni, Simona Panelli, Enza D’Auria, Miriam Acunzo, Ajay Ratan Pasala, Gian Vincenzo Zuccotti, Claudio Bandi and Lorenzo Drago

Int. J. Mol. Sci. 2021, 22(18), 9846; https://doi.org/10.3390/ijms22189846 - 12 Sep 2021

Cited by 25 | Viewed by 10285

Abstract

The human skin microbiota is essential for maintaining homeostasis and ensuring barrier functions. Over the years, the characterization of its composition and taxonomic diversity has reached outstanding goals, with more than 10 million bacterial genes collected and cataloged. Nevertheless, the study of the [...] Read more.

The human skin microbiota is essential for maintaining homeostasis and ensuring barrier functions. Over the years, the characterization of its composition and taxonomic diversity has reached outstanding goals, with more than 10 million bacterial genes collected and cataloged. Nevertheless, the study of the skin microbiota presents specific challenges that need to be addressed in study design. Benchmarking procedures and reproducible and robust analysis workflows for increasing comparability among studies are required. For various reasons and because of specific technical problems, these issues have been investigated in gut microbiota studies, but they have been largely overlooked for skin microbiota. After a short description of the skin microbiota, the review tackles methodological aspects and their pitfalls, covering NGS approaches and high throughput culture-based techniques. Recent insights into the “core” and “transient” types of skin microbiota and how the manipulation of these communities can prevent or combat skin diseases are also covered. Finally, this review includes an overview of the main dermatological diseases, the changes in the microbiota composition associated with them, and the recommended skin sampling procedures. The last section focuses on topical and oral probiotics to improve and maintain skin health, considering their possible applications for skin diseases. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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24 pages, 16052 KiB

Open AccessReview

The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host’s Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19

by Venera Z. Nezametdinova, Roman A. Yunes, Marina S. Dukhinova, Maria G. Alekseeva and Valery N. Danilenko

Int. J. Mol. Sci. 2021, 22(17), 9219; https://doi.org/10.3390/ijms22179219 - 26 Aug 2021

Cited by 11 | Viewed by 3446

Abstract

Bifidobacteria are some of the major agents that shaped the immune system of many members of the animal kingdom during their evolution. Over recent years, the question of concrete mechanisms underlying the immunomodulatory properties of bifidobacteria has been addressed in both animal and [...] Read more.

Bifidobacteria are some of the major agents that shaped the immune system of many members of the animal kingdom during their evolution. Over recent years, the question of concrete mechanisms underlying the immunomodulatory properties of bifidobacteria has been addressed in both animal and human studies. A possible candidate for this role has been discovered recently. The PFNA cluster, consisting of five core genes, pkb2, fn3, aaa-atp, duf58, tgm, has been found in all gut-dwelling autochthonous bifidobacterial species of humans. The sensory region of the species-specific serine-threonine protein kinase (PKB2), the transmembrane region of the microbial transglutaminase (TGM), and the type-III fibronectin domain-containing protein (FN3) encoded by the I gene imply that the PFNA cluster might be implicated in the interaction between bacteria and the host immune system. Moreover, the FN3 protein encoded by one of the genes making up the PFNA cluster, contains domains and motifs of cytokine receptors capable of selectively binding TNF-α. The PFNA cluster could play an important role for sensing signals of the immune system. Among the practical implications of this finding is the creation of anti-inflammatory drugs aimed at alleviating cytokine storms, one of the dire consequences resulting from SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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21 pages, 5629 KiB

Open AccessReview

The Gut Microbiota-Derived Immune Response in Chronic Liver Disease

by Sung-Min Won, Eunju Park, Jin-Ju Jeong, Raja Ganesan, Haripriya Gupta, Yoseph Asmelash Gebru, SatyaPriya Sharma, Dong-Joon Kim and Ki-Tae Suk

Int. J. Mol. Sci. 2021, 22(15), 8309; https://doi.org/10.3390/ijms22158309 - 2 Aug 2021

Cited by 16 | Viewed by 3366

Abstract

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet [...] Read more.

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut–liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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16 pages, 971 KiB

Open AccessReview

Gut Serpinome: Emerging Evidence in IBD

by Héla Mkaouar, Vincent Mariaule, Soufien Rhimi, Juan Hernandez, Aicha Kriaa, Amin Jablaoui, Nizar Akermi, Emmanuelle Maguin, Adam Lesner, Brice Korkmaz and Moez Rhimi

Int. J. Mol. Sci. 2021, 22(11), 6088; https://doi.org/10.3390/ijms22116088 - 4 Jun 2021

Cited by 12 | Viewed by 4064

Abstract

Inflammatory bowel diseases (IBD) are incurable disorders whose prevalence and global socioeconomic impact are increasing. While the role of host genetics and immunity is well documented, that of gut microbiota dysbiosis is increasingly being studied. However, the molecular basis of the dialogue between [...] Read more.

Inflammatory bowel diseases (IBD) are incurable disorders whose prevalence and global socioeconomic impact are increasing. While the role of host genetics and immunity is well documented, that of gut microbiota dysbiosis is increasingly being studied. However, the molecular basis of the dialogue between the gut microbiota and the host remains poorly understood. Increased activity of serine proteases is demonstrated in IBD patients and may contribute to the onset and the maintenance of the disease. The intestinal proteolytic balance is the result of an equilibrium between the proteases and their corresponding inhibitors. Interestingly, the serine protease inhibitors (serpins) encoded by the host are well reported; in contrast, those from the gut microbiota remain poorly studied. In this review, we provide a concise analysis of the roles of serine protease in IBD physiopathology and we focus on the serpins from the gut microbiota (gut serpinome) and their relevance as a promising therapeutic approach. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition)

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16 pages, 1737 KiB

Open AccessReview

Microbiota: Overview and Implication in Immunotherapy-Based Cancer Treatments

by Giovanni Brandi and Giorgio Frega

Int. J. Mol. Sci. 2019, 20(11), 2699; https://doi.org/10.3390/ijms20112699 - 31 May 2019

Cited by 24 | Viewed by 5314

Abstract

During the last few years, the gut microbiota has gained increasing attention as a consequence of its emerging role as a modulator of the immune system. With the advent of the era of checkpoint inhibitors immunotherapy and adoptive cell transfer (ACT) in oncology, [...] Read more.

During the last few years, the gut microbiota has gained increasing attention as a consequence of its emerging role as a modulator of the immune system. With the advent of the era of checkpoint inhibitors immunotherapy and adoptive cell transfer (ACT) in oncology, these findings became of primary relevance in light of experimental data that suggested the microbiota involvement as a plausible predictor of a good or poor response. These remarks justify the efforts to pinpoint the specific actions of the microbiota and to identify new strategies to favorably edit its composition. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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14 pages, 1065 KiB

Open AccessReview

Dysbiosis Disrupts Gut Immune Homeostasis and Promotes Gastric Diseases

by Devinder Toor, Mishi Kaushal Wsson, Prashant Kumar, G. Karthikeyan, Naveen Kumar Kaushik, Chhavi Goel, Sandhya Singh, Anil Kumar and Hridayesh Prakash

Int. J. Mol. Sci. 2019, 20(10), 2432; https://doi.org/10.3390/ijms20102432 - 16 May 2019

Cited by 88 | Viewed by 17579

Abstract

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and also promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in [...] Read more.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and also promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in the host, which in turn influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics, chemotherapeutic drugs, and any change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromilieu. Ligands released from dying microbes induce Toll-like receptor (TLR) mimicry, skew hypoxia, and cause sterile inflammation, which further contributes to the severity of inflammatory, autoimmune, and tumorous diseases. The major aim and scope of this review is both to discuss various modalities/interventions across the globe and to utilize microbiota-based therapeutic approaches for mitigating the disease burden. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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10 pages, 447 KiB

Open AccessReview

The Possible Role of Gut Microbiota and Microbial Translocation Profiling During Chemo-Free Treatment of Lymphoid Malignancies

by Valentina Zuccaro, Andrea Lombardi, Erika Asperges, Paolo Sacchi, Piero Marone, Alessandra Gazzola, Luca Arcaini and Raffaele Bruno

Int. J. Mol. Sci. 2019, 20(7), 1748; https://doi.org/10.3390/ijms20071748 - 9 Apr 2019

Cited by 3 | Viewed by 3396

Abstract

The crosstalk between gut microbiota (GM) and the immune system is intense and complex. When dysbiosis occurs, the resulting pro-inflammatory environment can lead to bacterial translocation, systemic immune activation, tissue damage, and cancerogenesis. GM composition seems to impact both the therapeutic activity and [...] Read more.

The crosstalk between gut microbiota (GM) and the immune system is intense and complex. When dysbiosis occurs, the resulting pro-inflammatory environment can lead to bacterial translocation, systemic immune activation, tissue damage, and cancerogenesis. GM composition seems to impact both the therapeutic activity and the side effects of anticancer treatment; in particular, robust evidence has shown that the GM modulates the response to immunotherapy in patients affected by metastatic melanoma. Despite accumulating knowledge supporting the role of GM composition in lymphomagenesis, unexplored areas still remain. No studies have been designed to investigate GM alteration in patients diagnosed with lymphoproliferative disorders and treated with chemo-free therapies, and the potential association between GM, therapy outcome, and immune-related adverse events has never been analyzed. Additional studies should be considered to create opportunities for a more tailored approach in this set of patients. In this review, we describe the possible role of the GM during chemo-free treatment of lymphoid malignancies. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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10 pages, 1137 KiB

Open AccessReview

Interactions between Host Immunity and Skin-Colonizing Staphylococci: No Two Siblings Are Alike

by Young Joon Park, Chae Won Kim and Heung Kyu Lee

Int. J. Mol. Sci. 2019, 20(3), 718; https://doi.org/10.3390/ijms20030718 - 7 Feb 2019

Cited by 5 | Viewed by 8477

Abstract

As the outermost layer of the body, the skin harbors innumerable and varied microorganisms. These microorganisms interact with the host, and these interactions contribute to host immunity. One of the most abundant genera of skin commensals is Staphylococcus. Bacteria belonging to this [...] Read more.

As the outermost layer of the body, the skin harbors innumerable and varied microorganisms. These microorganisms interact with the host, and these interactions contribute to host immunity. One of the most abundant genera of skin commensals is Staphylococcus. Bacteria belonging to this genus are some of the most influential commensals that reside on the skin. For example, colonization by Staphylococcus aureus, a well-known pathogen, increases inflammatory responses within the skin. Conversely, colonization by Staphylococcus epidermis, a coagulase-negative staphylococcal species that are prevalent throughout the skin, can be innocuous or beneficial. Thus, manipulating the abundance of these two bacterial species likely alters the skin microbiome and modulates the cutaneous immune response, with potential implications for various inflammation-associated skin diseases. Importantly, before researchers can begin manipulating the skin microbiome to prevent and treat disease, they must first fully understand how these two species can modulate the cutaneous immune response. In this review, we discuss the nature of the interactions between these two bacterial species and immune cells within the skin, discussing their immunogenicity within the context of skin disorders. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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16 pages, 920 KiB

Open AccessReview

The Interplay between Immunity and Microbiota at Intestinal Immunological Niche: The Case of Cancer

by Rossella Cianci, Laura Franza, Giovanni Schinzari, Ernesto Rossi, Gianluca Ianiro, Giampaolo Tortora, Antonio Gasbarrini, Giovanni Gambassi and Giovanni Cammarota

Int. J. Mol. Sci. 2019, 20(3), 501; https://doi.org/10.3390/ijms20030501 - 24 Jan 2019

Cited by 38 | Viewed by 8212

Abstract

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is [...] Read more.

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is then able to enhance inflammation and to influence gene expression. At the same time, there is an intense cross-talk between the microbiota and the immunological niche in the intestinal mucosa. These interactions may pave the way to the development, growth and spreading of cancer, especially in the gastro-intestinal system. Here, we review the changes in microbiota composition, how they relate to the immunological imbalance, influencing the onset of different types of cancer and the impact of these mechanisms on the efficacy of traditional and upcoming cancer treatments. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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16 pages, 985 KiB

Open AccessReview

Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature

by Ivana Milosevic, Ankica Vujovic, Aleksandra Barac, Marina Djelic, Milos Korac, Aleksandra Radovanovic Spurnic, Ivana Gmizic, Olja Stevanovic, Vladimir Djordjevic, Nebojsa Lekic, Edda Russo and Amedeo Amedei

Int. J. Mol. Sci. 2019, 20(2), 395; https://doi.org/10.3390/ijms20020395 - 17 Jan 2019

Cited by 352 | Viewed by 24142

Abstract

The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called “the new virtual metabolic organ”, makes axis with a number of extraintestinal organs, such as [...] Read more.

The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called “the new virtual metabolic organ”, makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of “ancient” microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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28 pages, 359 KiB

Open AccessReview

Recent Advances on Microbiota Involvement in the Pathogenesis of Autoimmunity

by Elena Gianchecchi and Alessandra Fierabracci

Int. J. Mol. Sci. 2019, 20(2), 283; https://doi.org/10.3390/ijms20020283 - 11 Jan 2019

Cited by 53 | Viewed by 6383

Abstract

Autoimmune disorders derive from genetic, stochastic, and environmental factors that all together interact in genetically predisposed individuals. The impact of an imbalanced gut microbiome in the pathogenesis of autoimmunity has been suggested by an increasing amount of experimental evidence, both in animal models [...] Read more.

Autoimmune disorders derive from genetic, stochastic, and environmental factors that all together interact in genetically predisposed individuals. The impact of an imbalanced gut microbiome in the pathogenesis of autoimmunity has been suggested by an increasing amount of experimental evidence, both in animal models and humans. Several physiological mechanisms, including the establishment of immune homeostasis, are influenced by commensal microbiota in the gut. An altered microbiota composition produces effects in the gut immune system, including defective tolerance to food antigens, intestinal inflammation, and enhanced gut permeability. In particular, early findings reported differences in the intestinal microbiome of subjects affected by several autoimmune conditions, including prediabetes or overt disease compared to healthy individuals. The present review focuses on microbiota-host homeostasis, its alterations, factors that influence its composition, and putative involvement in the development of autoimmune disorders. In the light of the existing literature, future studies are necessary to clarify the role played by microbiota modifications in the processes that cause enhanced gut permeability and molecular mechanisms responsible for autoimmunity onset. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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13 pages, 235 KiB

Open AccessReview

Interplay among Vaginal Microbiome, Immune Response and Sexually Transmitted Viral Infections

by Maria Gabriella Torcia

Int. J. Mol. Sci. 2019, 20(2), 266; https://doi.org/10.3390/ijms20020266 - 11 Jan 2019

Cited by 132 | Viewed by 11618

Abstract

The vaginal ecosystem is important for women’s health and for a successful reproductive life, and an optimal host-microbial interaction is required for the maintenance of eubiosis. The vaginal microbiota is dominated by Lactobacillus species in the majority of women. Loss of Lactobacillus dominance [...] Read more.

The vaginal ecosystem is important for women’s health and for a successful reproductive life, and an optimal host-microbial interaction is required for the maintenance of eubiosis. The vaginal microbiota is dominated by Lactobacillus species in the majority of women. Loss of Lactobacillus dominance promotes the colonization by anaerobic bacterial species with an increase in microbial diversity. Vaginal dysbiosis is a very frequent condition which affects the immune homeostasis, inducing a rupture in the epithelial barrier and favoring infection by sexually transmitted pathogens. In this review, we describe the known interactions among immune cells and microbial commensals which govern health or disease status. Particular attention is given to microbiota compositions which, through interplay with immune cells, facilitate the establishment of viral infections, such as Human Immunodeficiency Virus (HIV), Human Papilloma Virus (HPV), Herpes Simplex Virus 2 (HSV2). Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

12 pages, 232 KiB

Open AccessReview

Bacteriocins and Bacteriophages: Therapeutic Weapons for Gastrointestinal Diseases?

by Loris Riccardo Lopetuso, Maria Ernestina Giorgio, Angela Saviano, Franco Scaldaferri, Antonio Gasbarrini and Giovanni Cammarota

Int. J. Mol. Sci. 2019, 20(1), 183; https://doi.org/10.3390/ijms20010183 - 6 Jan 2019

Cited by 70 | Viewed by 6990

Abstract

Bacteriocins are bactericidal peptides, ribosomally synthesized, with an inhibitory activity against diverse groups of undesirable microorganisms. Bacteriocins are produced by both gram-positive and gram-negative bacteria, and to a lesser extent by some archaea. Bacteriophages are viruses that are able to infect bacterial cells [...] Read more.

Bacteriocins are bactericidal peptides, ribosomally synthesized, with an inhibitory activity against diverse groups of undesirable microorganisms. Bacteriocins are produced by both gram-positive and gram-negative bacteria, and to a lesser extent by some archaea. Bacteriophages are viruses that are able to infect bacterial cells and force them to produce viral components, using a lytic or lysogenic cycle. They constitute a large community in the human gut called the phageome, the most abundant part of the gut virome. Bacteriocins and bacteriophages may have an influence on both human health and diseases, thanks to their ability to modulate the gut microbiota and regulate the competitive relationship among the different microorganisms, strains and cells living in the human intestine. In this review, we explore the role of bacteriocins and bacteriophages in the most frequent gastrointestinal diseases by dissecting their interaction with the complex environment of the human gut, analyzing a possible link with extra-intestinal diseases, and speculating on their possible therapeutic application with the end goal of promoting gut health. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

13 pages, 1041 KiB

Open AccessReview

I’ve Gut A Feeling: Microbiota Impacting the Conceptual and Experimental Perspectives of Personalized Medicine

by Amedeo Amedei and Federico Boem

Int. J. Mol. Sci. 2018, 19(12), 3756; https://doi.org/10.3390/ijms19123756 - 27 Nov 2018

Cited by 35 | Viewed by 6055

Abstract

In recent years, the human microbiota has gained increasing relevance both in research and clinical fields. Increasing studies seem to suggest the centrality of the microbiota and its composition both in the development and maintenance of what we call “health” and in generating [...] Read more.

In recent years, the human microbiota has gained increasing relevance both in research and clinical fields. Increasing studies seem to suggest the centrality of the microbiota and its composition both in the development and maintenance of what we call “health” and in generating and/or favoring (those cases in which the microbiota’s complex relational architecture is dysregulated) the onset of pathological conditions. The complex relationships between the microbiota and human beings, which invest core notions of biomedicine such as “health” and “individual,” do concern not only problems of an empirical nature but seem to require the need to adopt new concepts and new perspectives in order to be properly analysed and utilized, especially for their therapeutic implementation. In this contribution we report and discuss some of the theoretical proposals and innovations (from the ecological component to the notion of polygenomic organism) aimed at producing this change of perspective. In conclusion, we summarily analyze what impact and what new challenges these new approaches might have on personalized/person centred/precision medicine. Full article

(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases)

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