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Molecular and Cellular Mechanisms Underlying Probiotic Activity

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

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 18873

Special Issue Editor


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Guest Editor
Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, 71122 Foggia, Italy
Interests: probiotics; lactic acid bacteria; host-probiotic interactions; prebiotics; stress response; small heat shock proteins; melanogenesis; antimicrobial activity
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Special Issue Information

Dear Colleagues,

Basic and clinical studies have been providing increasing evidence that probiotic microorganisms can improve host health, e.g. by supporting the natural physiology of some organs and by preventing certain diseases. Indeed, many scientific papers document that probiotics—as live cells and, more recently, in the form of inactivated cells, cell components, and metabolites (i.e., paraprobiotics and postbiotics, respectively)—can balance the gut microbiota, reinforce the barrier function of gut mucosa, modulate the immune response, exert antitumor and anti-oxidant activity, and participate in gut–brain signaling. However, information on the mechanisms of action of probiotics and postbiotics remains limited and current research must now focus on the specific molecular players involved in the host–microbe crosstalk and underlying the health-promoting effects. Thus, it is necessary to characterize both the probiotic-derived molecules that trigger host response, as well as the host cell receptors and related molecular pathways that they stimulate.

Most of the key probiotic effectors identified so far are secreted metabolites and/or molecules located on the microbial cell surface including pili and fimbriae-like structures, surface structural proteins, lipoteichoic acids, exopolysaccharides, short-chain fatty acids, bacteriocins, and other antimicrobial agents. These microbial molecules have been found to interact with host cell receptors such as members of the Toll-like receptor (TLR) family, NODs, and DC-SIGN, leading to the modulation of signaling related to MAPK and NF-κB pathways. Yet, the molecular and cellular mechanisms underlying the beneficial effects of probiotics deserve deeper investigation, and this will be fundamental to implement the application of probiotics in clinical settings, to increase reproducibility of the studies, and to select targeted strains with specific attributes.

This Special Issue will present the recent progress on this topic, collecting both original research and review articles.

Dr. Daniela Fiocco
Guest Editor

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Keywords

  • probiotics
  • postbiotics
  • host-probiotic interaction
  • host cell receptors
  • signaling
  • microbial secreted metabolites
  • microbial cell surface
  • immune cells
  • immune-modulatory activity
  • lactobacilli
  • bifidobateria
  • peptidoglycan
  • exo-polysaccharides
  • pili
  • teichoic acids

Published Papers (5 papers)

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Research

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15 pages, 3216 KiB  
Article
Bifidobacterium longum subsp. infantis CECT 7210 Reduces Inflammatory Cytokine Secretion in Caco-2 Cells Cultured in the Presence of Escherichia coli CECT 515
by Ana I. Álvarez-Mercado, Julio Plaza-Díaz, M. Cristina de Almagro, Ángel Gil, José Antonio Moreno-Muñoz and Luis Fontana
Int. J. Mol. Sci. 2022, 23(18), 10813; https://doi.org/10.3390/ijms231810813 - 16 Sep 2022
Cited by 4 | Viewed by 2032
Abstract
Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present [...] Read more.
Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms Underlying Probiotic Activity)
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17 pages, 4515 KiB  
Article
Exopolysaccharides of Bacillus amyloliquefaciens Amy-1 Mitigate Inflammation by Inhibiting ERK1/2 and NF-κB Pathways and Activating p38/Nrf2 Pathway
by Wei-Wen Sung, Yun-Yu Lin, Shen-Da Huang and Hsueh-Ling Cheng
Int. J. Mol. Sci. 2022, 23(18), 10237; https://doi.org/10.3390/ijms231810237 - 6 Sep 2022
Cited by 4 | Viewed by 1420
Abstract
Bacillus amyloliquefaciens is a probiotic for animals. Evidence suggests that diets supplemented with B. amyloliquefaciens can reduce inflammation; however, the underlying mechanism is unclear and requires further exploration. The exopolysaccharides of B. amyloliquefaciens amy-1 displayed hypoglycemic activity previously, suggesting that they are bioactive [...] Read more.
Bacillus amyloliquefaciens is a probiotic for animals. Evidence suggests that diets supplemented with B. amyloliquefaciens can reduce inflammation; however, the underlying mechanism is unclear and requires further exploration. The exopolysaccharides of B. amyloliquefaciens amy-1 displayed hypoglycemic activity previously, suggesting that they are bioactive molecules. In addition, they counteracted the effect of lipopolysaccharide (LPS) on inducing cellular insulin resistance in exploratory tests. Therefore, this study aimed to explore the anti-inflammatory effect and molecular mechanisms of the exopolysaccharide preparation of amy-1 (EPS). Consequently, EPS reduced the expression of proinflammatory factors, the phagocytic activity and oxidative stress of LPS-stimulated THP-1 cells. In animal tests, EPS effectively ameliorated ear inflammation of mice. These data suggested that EPS possess anti-inflammatory activity. A mechanism study revealed that EPS inhibited the nuclear factor-κB pathway, activated the mitogen-activated protein kinase (MAPK) p38, and prohibited the extracellular signal-regulated kinase 1/2, but had no effect on the c-Jun-N-terminal kinase 2 (JNK). EPS also activated the anti-oxidative nuclear factor erythroid 2–related factor 2 (Nrf2) pathway. Evidence suggested that p38, but not JNK, was involved in activating the Nrf2 pathway. Together, these mechanisms reduced the severity of inflammation. These findings support the proposal that exopolysaccharides may play important roles in the anti-inflammatory functions of probiotics. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms Underlying Probiotic Activity)
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Review

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19 pages, 957 KiB  
Review
Probiotics Function in Preventing Atopic Dermatitis in Children
by Caterina Anania, Giulia Brindisi, Ivana Martinelli, Edoardo Bonucci, Miriam D’Orsi, Sara Ialongo, Anna Nyffenegger, Tonia Raso, Mattia Spatuzzo, Giovanna De Castro, Anna Maria Zicari, Carlo Carraro, Maria Grazia Piccioni and Francesca Olivero
Int. J. Mol. Sci. 2022, 23(10), 5409; https://doi.org/10.3390/ijms23105409 - 12 May 2022
Cited by 18 | Viewed by 4830
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by relapsing eczematous injuries and severe pruritus. In the last few years, the AD prevalence has been increasing, reaching 20% in children and 10% in adults in high-income countries. Recently, the potential role [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by relapsing eczematous injuries and severe pruritus. In the last few years, the AD prevalence has been increasing, reaching 20% in children and 10% in adults in high-income countries. Recently, the potential role of probiotics in AD prevention has generated considerable interest. As many clinical studies show, the gut microbiota is able to modulate systemic inflammatory and immune responses influencing the development of sensitization and allergy. Probiotics are used increasingly against AD. However, the molecular mechanisms underlying the probiotics mediated anti-allergic effect remain unclear and there is controversy about their efficacy. In this narrative review, we examine the actual evidence on the effect of probiotic supplementation for AD prevention in the pediatric population, discussing also the potential biological mechanisms of action in this regard. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms Underlying Probiotic Activity)
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24 pages, 2025 KiB  
Review
Probiotics as Potential Biological Immunomodulators in the Management of Oral Lichen Planus: What’s New?
by Paola Zanetta, Margherita Ormelli, Angela Amoruso, Marco Pane, Barbara Azzimonti and Diletta Francesca Squarzanti
Int. J. Mol. Sci. 2022, 23(7), 3489; https://doi.org/10.3390/ijms23073489 - 23 Mar 2022
Cited by 7 | Viewed by 4130
Abstract
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disorder with multifactorial aetiology and malignant transformation potential. Despite the treatments so far identified, new tailored and safe specific measures are needed. Recently, human microbiota imbalance has been linked to several immune-mediated diseases, [...] Read more.
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disorder with multifactorial aetiology and malignant transformation potential. Despite the treatments so far identified, new tailored and safe specific measures are needed. Recently, human microbiota imbalance has been linked to several immune-mediated diseases, opening new therapeutic perspectives for probiotics; besides their ability to directly interact with the host microbiota, they also display a strain-specific immune-modulatory effect. Thus, this non-systematic review aims to elucidate the molecular pathways underlying probiotic activity, mainly those of Lactobacilli and Bifidobacteria and their metabolites in OLP pathogenesis and malignant transformation, focusing on the most recent in vitro and in vivo research evidence. Findings related to their activity in other immune-mediated diseases are here included, suggesting a probiotic translational use in OLP. Probiotics show immune-modulatory and microbiota-balancing activities; they protect the host from pathogens, hamper an excessive effector T cell response, reduce nuclear factor-kappa B (NF-kB) signalling and basal keratinocytes abnormal apoptosis, shifting the mucosal response towards the production of anti-inflammatory cytokines, thus preventing uncontrolled damage. Therefore, probiotics could be a highly encouraging prevention and immunotherapeutic approach for a safer and more sustainable OLP management. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms Underlying Probiotic Activity)
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30 pages, 1930 KiB  
Review
Bioprospecting Antimicrobials from Lactiplantibacillus plantarum: Key Factors Underlying Its Probiotic Action
by Maria Teresa Rocchetti, Pasquale Russo, Vittorio Capozzi, Djamel Drider, Giuseppe Spano and Daniela Fiocco
Int. J. Mol. Sci. 2021, 22(21), 12076; https://doi.org/10.3390/ijms222112076 - 8 Nov 2021
Cited by 26 | Viewed by 5726
Abstract
Lactiplantibacillus plantarum (L. plantarum) is a well-studied and versatile species of lactobacilli. It is found in several niches, including human mucosal surfaces, and it is largely employed in the food industry and boasts a millenary tradition of safe use, sharing a [...] Read more.
Lactiplantibacillus plantarum (L. plantarum) is a well-studied and versatile species of lactobacilli. It is found in several niches, including human mucosal surfaces, and it is largely employed in the food industry and boasts a millenary tradition of safe use, sharing a long-lasting relationship with humans. L. plantarum is generally recognised as safe and exhibits a strong probiotic character, so that several strains are commercialised as health-promoting supplements and functional food products. For these reasons, L. plantarum represents a valuable model to gain insight into the nature and mechanisms of antimicrobials as key factors underlying the probiotic action of health-promoting microbes. Probiotic antimicrobials can inhibit the growth of pathogens in the gut ensuring the intestinal homeostasis and contributing to the host health. Furthermore, they may be attractive alternatives to conventional antibiotics, holding potential in several biomedical applications. The aim of this review is to investigate the most relevant papers published in the last ten years, bioprospecting the antimicrobial activity of characterised probiotic L. plantarum strains. Specifically, it focuses on the different chemical nature, the action spectra and the mechanisms underlying the bioactivity of their antibacterial and antiviral agents. Emerging trends in postbiotics, some in vivo applications of L. plantarum antimicrobials, including strengths and limitations of their therapeutic potential, are addressed and discussed. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms Underlying Probiotic Activity)
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