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The Role of Microbiota in Immunity and Inflammation
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The Role of Microbiota in Immunity and Inflammation

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: 20 December 2024 | Viewed by 10952

Special Issue Editors

Dr. Veronica Marrella

E-Mail Website
Guest Editor
UOS Milan Unit, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, 20138 Milan, Italy
Interests: immunity; senescence; inflammation; autoimmunity; microbiota
Dr. Barbara Cassani

E-Mail Website
Guest Editor
Department of Medical Biotechnologies and Translational Medicine, Università Degli Studi di Milano, 20089 Milan, Italy
Interests: adaptive immunity; immune tolerance, microbiota dysbiosis; infections, immune-mediated disease; cellular senescence
Dr. Francesca Pala

E-Mail Website
Guest Editor
Laboratory of Clinical Immunology and Microbiology (LCIM), NIAID, NIH, Bethesda, MD 20892, USA
Interests: immunodeficiencies; immune dysregulation; T cell deficiencies; thymus; microbiota

Special Issue Information

Dear Colleagues,

Commensal microbiota and the immune system are closely related; indeed, the microbiota takes part in the development, education, and function of the host immune system, which in turn has evolved to ensure host–microbe symbiosis. This alliance allows for protective responses against pathogens and supports regulatory pathways in maintaining tolerance to harmless antigens. On the other hand, environmental factors, host–microbiome interfaces, and a defective immune system can cause microbiota disturbance, leading to dysbiosis, systemic dissemination of commensal microorganisms, predisposition to pathogens invasion, and inflammation. A persistent imbalance in the microbiota’s functional composition contributes to the rise and progression of different human pathologies. In the last few years, advances in multi-omics approaches have increased our understanding of microbiota variations in disease. However, the mechanisms underlying its interactions with the host remain incompletely understood. In this Special Issue, authors are encouraged to focus on the complex role of the microbiota as the regulator of immune response in health and disease. We welcome studies that go beyond the description of changes in microbial communities and provide mechanistic insights into how their interaction with the host physiology translates into control of systemic and tissue-specific immunity.

Moreover, we encourage papers dealing with the refinement of clinical approaches or novel potential therapeutic avenues to preserve or restore microbiota–immune system interplay during pathological states.

Dr. Veronica Marrella
Dr. Barbara Cassani
Dr. Francesca Pala
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbiota
  • metabolites
  • antimicrobial peptides
  • innate/adaptive immunity
  • inflammatory diseases
  • infections
  • cytokines

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Published Papers (4 papers)

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16 pages, 8178 KiB  
Article
A New Probiotic Formulation Promotes Resolution of Inflammation in a Crohn’s Disease Mouse Model by Inducing Apoptosis in Mucosal Innate Immune Cells
by Carlo De Salvo, Abdullah Osme, Mahmoud Ghannoum, Fabio Cominelli and Luca Di Martino
Int. J. Mol. Sci. 2024, 25(22), 12066; https://doi.org/10.3390/ijms252212066 - 10 Nov 2024
Viewed by 450
Abstract
The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn’s disease (CD), where microbiome dysregulation can alter immune responses, leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of a recently developed [...] Read more.
The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn’s disease (CD), where microbiome dysregulation can alter immune responses, leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of a recently developed probiotic + amylase blend in the SAMP1/YitFc (SAMP) mouse model of CD-like ileitis. Four groups of SAMP mice were gavaged for 56 days with the following treatments: 1) probiotic strains + amylase (0.25 mg/100 µL PBS); 2) only probiotics; 3) only amylase; PBS-treated controls. Ilea were collected for GeoMx Digital Spatial Profiler (DSP) analysis and histological evaluation. Histology assessment for inflammation indicated a significantly reduced level of ileitis in mice administered the probiotics + amylase blend. DSP analysis showed decreased abundance of neutrophils and increased abundance of dendritic cells, regulatory T cells, and macrophages, with a significant enrichment of five intracellular pathways related to apoptosis, in probiotics + amylase-treated mice. Increased apoptosis occurrence was confirmed by (TdT)- deoxyuridine triphosphate (dUTP)-biotin nick end labeling assay. Our data demonstrate a beneficial role of the probiotic and amylase blend, highlighting an increased apoptosis of innate immunity-associated cell subsets, thus promoting the resolution of inflammation. Hence, we suggest that the developed probiotic enzyme blend may be a therapeutic tool to manage CD and therefore is a candidate formulation to be tested in clinical trials. Full article
(This article belongs to the Special Issue The Role of Microbiota in Immunity and Inflammation)
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Review

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20 pages, 1103 KiB  
Review
Exploring the Gut Microbiota–Muscle Axis in Duchenne Muscular Dystrophy
by Debora Mostosi, Monica Molinaro, Sabrina Saccone, Yvan Torrente, Chiara Villa and Andrea Farini
Int. J. Mol. Sci. 2024, 25(11), 5589; https://doi.org/10.3390/ijms25115589 - 21 May 2024
Viewed by 2258
Abstract
The gut microbiota plays a pivotal role in maintaining the dynamic balance of intestinal epithelial and immune cells, crucial for overall organ homeostasis. Dysfunctions in these intricate relationships can lead to inflammation and contribute to the pathogenesis of various diseases. Recent findings uncovered [...] Read more.
The gut microbiota plays a pivotal role in maintaining the dynamic balance of intestinal epithelial and immune cells, crucial for overall organ homeostasis. Dysfunctions in these intricate relationships can lead to inflammation and contribute to the pathogenesis of various diseases. Recent findings uncovered the existence of a gut–muscle axis, revealing how alterations in the gut microbiota can disrupt regulatory mechanisms in muscular and adipose tissues, triggering immune-mediated inflammation. In the context of Duchenne muscular dystrophy (DMD), alterations in intestinal permeability stand as a potential origin of molecules that could trigger muscle degeneration via various pathways. Metabolites produced by gut bacteria, or fragments of bacteria themselves, may have the ability to migrate from the gut into the bloodstream and ultimately infiltrate distant muscle tissues, exacerbating localized pathologies. These insights highlight alternative pathological pathways in DMD beyond the musculoskeletal system, paving the way for nutraceutical supplementation as a potential adjuvant therapy. Understanding the complex interplay between the gut microbiota, immune system, and muscular health offers new perspectives for therapeutic interventions beyond conventional approaches to efficiently counteract the multifaceted nature of DMD. Full article
(This article belongs to the Special Issue The Role of Microbiota in Immunity and Inflammation)
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30 pages, 1661 KiB  
Review
Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair
by Veronica Marrella, Federico Nicchiotti and Barbara Cassani
Int. J. Mol. Sci. 2024, 25(7), 4051; https://doi.org/10.3390/ijms25074051 - 5 Apr 2024
Cited by 10 | Viewed by 4091
Abstract
Bacterial and viral respiratory tract infections are the most common infectious diseases, leading to worldwide morbidity and mortality. In the past 10 years, the importance of lung microbiota emerged in the context of pulmonary diseases, although the mechanisms by which it impacts the [...] Read more.
Bacterial and viral respiratory tract infections are the most common infectious diseases, leading to worldwide morbidity and mortality. In the past 10 years, the importance of lung microbiota emerged in the context of pulmonary diseases, although the mechanisms by which it impacts the intestinal environment have not yet been fully identified. On the contrary, gut microbial dysbiosis is associated with disease etiology or/and development in the lung. In this review, we present an overview of the lung microbiome modifications occurring during respiratory infections, namely, reduced community diversity and increased microbial burden, and of the downstream consequences on host–pathogen interaction, inflammatory signals, and cytokines production, in turn affecting the disease progression and outcome. Particularly, we focus on the role of the gut–lung bidirectional communication in shaping inflammation and immunity in this context, resuming both animal and human studies. Moreover, we discuss the challenges and possibilities related to novel microbial-based (probiotics and dietary supplementation) and microbial-targeted therapies (antibacterial monoclonal antibodies and bacteriophages), aimed to remodel the composition of resident microbial communities and restore health. Finally, we propose an outlook of some relevant questions in the field to be answered with future research, which may have translational relevance for the prevention and control of respiratory infections. Full article
(This article belongs to the Special Issue The Role of Microbiota in Immunity and Inflammation)
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24 pages, 1911 KiB  
Review
Interplay between Microbiota and γδ T Cells: Insights into Immune Homeostasis and Neuro-Immune Interactions
by Alaa A. Mohamed, Basel K. al-Ramadi and Maria J. Fernandez-Cabezudo
Int. J. Mol. Sci. 2024, 25(3), 1747; https://doi.org/10.3390/ijms25031747 - 1 Feb 2024
Cited by 6 | Viewed by 3442
Abstract
The gastrointestinal (GI) tract of multicellular organisms, especially mammals, harbors a symbiotic commensal microbiota with diverse microorganisms including bacteria, fungi, viruses, and other microbial and eukaryotic species. This microbiota exerts an important role on intestinal function and contributes to host health. The microbiota, [...] Read more.
The gastrointestinal (GI) tract of multicellular organisms, especially mammals, harbors a symbiotic commensal microbiota with diverse microorganisms including bacteria, fungi, viruses, and other microbial and eukaryotic species. This microbiota exerts an important role on intestinal function and contributes to host health. The microbiota, while benefiting from a nourishing environment, is involved in the development, metabolism and immunity of the host, contributing to the maintenance of homeostasis in the GI tract. The immune system orchestrates the maintenance of key features of host–microbe symbiosis via a unique immunological network that populates the intestinal wall with different immune cell populations. Intestinal epithelium contains lymphocytes in the intraepithelial (IEL) space between the tight junctions and the basal membrane of the gut epithelium. IELs are mostly CD8+ T cells, with the great majority of them expressing the CD8αα homodimer, and the γδ T cell receptor (TCR) instead of the αβ TCR expressed on conventional T cells. γδ T cells play a significant role in immune surveillance and tissue maintenance. This review provides an overview of how the microbiota regulates γδ T cells and the influence of microbiota-derived metabolites on γδ T cell responses, highlighting their impact on immune homeostasis. It also discusses intestinal neuro-immune regulation and how γδ T cells possess the ability to interact with both the microbiota and brain. Full article
(This article belongs to the Special Issue The Role of Microbiota in Immunity and Inflammation)
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