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19 pages, 6650 KiB  
Article
Multi-Strain Probiotic Regulates the Intestinal Mucosal Immunity and Enhances the Protection of Piglets Against Porcine Epidemic Diarrhea Virus Challenge
by Xueying Wang, Qi Zhang, Weijian Wang, Xiaona Wang, Baifen Song, Jiaxuan Li, Wen Cui, Yanping Jiang, Weichun Xie and Lijie Tang
Microorganisms 2025, 13(8), 1738; https://doi.org/10.3390/microorganisms13081738 - 25 Jul 2025
Viewed by 379
Abstract
Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, [...] Read more.
Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, Ligilactobacillus salivarius LSM231, and Lactiplantibacillus plantarum LPM239, which exhibited synergistic growth, potent acid/bile salt tolerance, and broad-spectrum antimicrobial activity against pathogens. In vitro, the probiotic combination disrupted pathogen ultrastructure and inhibited PEDV replication in IPI-2I cells. In vivo, PEDV-infected piglets administered with the multi-strain probiotic exhibited decreased viral loads in anal and nasal swabs, as well as in intestinal tissues. This intervention was associated with the alleviation of diarrhea symptoms and improved weight gain. Furthermore, the multi-strain probiotic facilitated the repair of intestinal villi and tight junctions, increased the number of goblet cells, downregulated pro-inflammatory cytokines, enhanced the expression of barrier proteins, and upregulated antiviral interferon-stimulated genes. These findings demonstrate that the multi-strain probiotic mitigates PEDV-induced damage by restoring intestinal barrier homeostasis and modulating immune responses, providing a novel strategy for controlling PEDV infections. Full article
(This article belongs to the Special Issue Viral Infection on Swine: Pathogenesis, Diagnosis and Control)
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21 pages, 2924 KiB  
Article
Mucosal Vaccination Against SARS-CoV-2 Using Human Probiotic Bacillus subtilis Spores as an Adjuvant Induces Potent Systemic and Mucosal Immunity
by Raul Ramos Pupo, Laura M. Reyes Diaz, Gisela M. Suarez Formigo, Yusnaby Borrego Gonzalez, Miriam Lastre Gonzalez, Danay Saavedra Hernandez, Tania Crombet Ramos, Belinda Sanchez Ramirez, Roberto Grau, Niels Hellings, Piet Stinissen, Oliver Perez and Jeroen F. J. Bogie
Vaccines 2025, 13(7), 772; https://doi.org/10.3390/vaccines13070772 - 21 Jul 2025
Viewed by 606
Abstract
Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain [...] Read more.
Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4+ and CD8+ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission. Full article
(This article belongs to the Special Issue Human Immune Responses to Infection and Vaccination)
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15 pages, 1279 KiB  
Systematic Review
The Efficacy and Safety of Probiotics in the Management of Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis
by Ali Abbas, Mohammed Abbas, Zahir Mughal, Pablo Martinez-Devesa and Ali Qureishi
J. Clin. Med. 2025, 14(14), 5001; https://doi.org/10.3390/jcm14145001 - 15 Jul 2025
Viewed by 569
Abstract
Background/Objectives: In this study, we aimed to evaluate probiotics’ clinical efficacy and safety in adults with chronic rhinosinusitis (CRS), and summarize mechanistic evidence related to mucosal immunity and microbiota modulation. Methods: We performed a systematic review and random-effects meta-analysis. MEDLINE, Embase, [...] Read more.
Background/Objectives: In this study, we aimed to evaluate probiotics’ clinical efficacy and safety in adults with chronic rhinosinusitis (CRS), and summarize mechanistic evidence related to mucosal immunity and microbiota modulation. Methods: We performed a systematic review and random-effects meta-analysis. MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched until May 2025. Eligibility: Randomized controlled trials (RCTs) and mechanistic studies investigating probiotics (any strain, dose, or administration route) in adults with CRS were eligible. Primary outcomes included changes in Sino-Nasal Outcome Test (SNOT-20/22) scores and CRS relapse rates. Secondary outcomes were adverse events and mechanistic endpoints. Results: Six studies (four RCTs, n = 337; two mechanistic studies) met the inclusion criteria. Probiotics did not significantly improve SNOT scores compared with the placebo, but trended in that direction (pooled mean difference—2.70; 95% CI −7.12 to 1.72; I2 = 0%). Furthermore, probiotic use was associated with a non-significant trend towards fewer CRS relapses (risk ratio 0.41; 95% CI 0.16–1.04; p = 0.06; I2 = 48%). Adverse events were mild and comparable to the placebo (risk ratio 0.87; 95% CI 0.33–2.34). Mechanistic data indicated that intranasal Lactococcus lactis W136 might downregulate type 1 inflammatory pathways and modestly increase microbiome diversity. Subgroup analyses (by route, duration, and CRS subtype) revealed no statistically significant effect modifiers, though mechanistic insights suggest possible differences in efficacy based on the CRS endotype and delivery method. Conclusions: Probiotics appear safe and may provide a small, non-significant improvement in CRS symptoms; emerging evidence of reduced relapse rates warrants further investigation through larger, endotype-stratified trials utilizing targeted probiotic strains and optimized delivery methods. Full article
(This article belongs to the Section Otolaryngology)
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24 pages, 2756 KiB  
Article
Nasal Rinsing with Probiotics—Microbiome Evaluation in Patients with Inflammatory Diseases of the Nasal Mucosa
by Eliza Brożek-Mądry, Laura Ziuzia-Januszewska, Oliwier Misztal, Zofia Burska, Ewelina Sosnowska-Turek and Janusz Sierdziński
J. Clin. Med. 2025, 14(10), 3341; https://doi.org/10.3390/jcm14103341 - 11 May 2025
Viewed by 1249
Abstract
Background/Objectives: The evidence regarding the efficacy of probiotics in chronic rhinosinusitis (CRS) is very limited, prompting the EPOS2020 steering group to advise against their use in CRS treatment. Therefore, further research to evaluate the impact of probiotics on microbial communities is particularly [...] Read more.
Background/Objectives: The evidence regarding the efficacy of probiotics in chronic rhinosinusitis (CRS) is very limited, prompting the EPOS2020 steering group to advise against their use in CRS treatment. Therefore, further research to evaluate the impact of probiotics on microbial communities is particularly important. This study aimed to assess the influence of probiotic nasal rinses on nasal microbiota profiles in patients with primary CRS, granulomatosis with polyangiitis (GPA), and nasal septal perforation (NSP) using 16S rRNA sequencing. Methods: Thirty-six patients with nasal mucosal diseases, including sixteen with primary CRS, eleven with GPA, and nine with NSP, were randomly assigned to either a study group receiving nasal rinses with probiotics containing Lactobacillus plantarum and Bifidobacterium animalis, or a control group using nasal rinses with saline. Metagenomic analysis targeting the V3–V4 hypervariable region of the 16S rRNA gene was performed to characterize bacterial and archaeal populations. Results: At the genus level, the most abundant co-colonizers included Staphylococcus, Streptococcus, and Haemophilus. After one month of probiotic rinsing, a decrease in abundance of the genera Finegoldia (p = 0.010), Haemophilus (p = 0.020), Streptococcus (p = 0.027), Staphylococcus (p = 0.033), Micrococcus (p = 0.035), Corynebacterium (p = 0.049), Gemella (p = 0.055), Rubrobacter (p = 0.055), and Pseudonocardia (p = 0.058) was observed. Conversely, the abundance of probiotic species Lactobacillus plantarum and Bifidobacterium animalis increased. Moreover, increases in the genera Dolosigranulum and Stenotrophomonas were observed, although they did not reach statistical significance. Conclusions: Probiotic nasal rinses may contribute to restoring microbial homeostasis by reducing genera associated with inflammatory dysbiosis in nasal inflammatory diseases, warranting further research on their clinical benefits. Full article
(This article belongs to the Section Otolaryngology)
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21 pages, 2387 KiB  
Article
Characterization and Probiotic Potential of Levilactobacillus brevis DPL5: A Novel Strain Isolated from Human Breast Milk with Antimicrobial Properties Against Biofilm-Forming Staphylococcus aureus
by Ivan Iliev, Galina Yahubyan, Elena Apostolova-Kuzova, Mariyana Gozmanova, Daniela Mollova, Iliya Iliev, Lena Ilieva, Mariana Marhova, Velizar Gochev and Vesselin Baev
Microorganisms 2025, 13(1), 160; https://doi.org/10.3390/microorganisms13010160 - 14 Jan 2025
Cited by 3 | Viewed by 1798
Abstract
Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated Levilactobacillus brevis DPL5 strain from human breast milk, focusing on its ability [...] Read more.
Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated Levilactobacillus brevis DPL5 strain from human breast milk, focusing on its ability to combat biofilm-forming pathogens such as Staphylococcus aureus. Employing in vitro approaches, we demonstrate L. brevis DPL5′s ability to endure at pH 3 with survival rates above 30%, and withstand the osmotic stress often found during industrial processes like fermentation and freeze drying, retaining over 90% viability. The lyophilized cell-free supernatant of L. brevis DPL5 had a significant antagonistic effect against biofilm-producing nasal strains of Staphylococcus aureus, and it completely eradicated biofilms at subinhibitory concentrations of 20 mg·mL−1. Higher concentrations of 69 mg·mL−1 were found to have a 99% bactericidal effect, based on the conducted probability analysis, indicating the production of bactericidal bioactive extracellular compounds capable of disrupting the biofilm formation of pathogens like S. aureus. Furthermore, genome-wide sequencing and analysis of L. brevis DPL5 with cutting-edge Nanopore technology has uncovered over 50 genes linked to probiotic activity, supporting its ability to adapt and thrive in the harsh gut environment. The genome also contains multiple biosynthetic gene clusters such as lanthipeptide class IV, Type III polyketide synthase (T3PKS), and ribosomally synthesized, and post-translationally modified peptides (RiPP-like compounds), all of which are associated with antibacterial properties. Our study paves the way for the further exploration of DPL5, setting the stage for innovative, nature-inspired solutions to combat stubborn bacterial infections. Full article
(This article belongs to the Special Issue Beneficial Microorganisms and Antimicrobials: 2nd Edition)
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16 pages, 287 KiB  
Article
Nutrient Supplements for Young Children and Mothers’ Self Medication with Over-the-Counter Drugs During the COVID-19 Pandemic
by Esin Aydın Aksoy, Bahar Güçiz Doğan and Sıddıka Songül Yalçın
Nutrients 2024, 16(23), 4182; https://doi.org/10.3390/nu16234182 - 2 Dec 2024
Cited by 4 | Viewed by 1643
Abstract
Background: The restriction of access to health services during the COVID-19 pandemic has led to an increase in self-medication. This study aims to examine mothers’ use of nutrient supplements with over-the-counter (OTC) medications for their children, including instances of self-medication for themselves. The [...] Read more.
Background: The restriction of access to health services during the COVID-19 pandemic has led to an increase in self-medication. This study aims to examine mothers’ use of nutrient supplements with over-the-counter (OTC) medications for their children, including instances of self-medication for themselves. The study also explores maternal characteristics associated with this behavior, the specific medications used, and the reasons for use. Method: In this descriptive study, 450 mothers with children aged 2 to 6 years in Türkiye were recruited through social media platforms. Questions focused on whether mothers used supplements for themselves and their children, types of products, frequency, and reasons for use. Multivariable binary logistic regression was conducted to examine the factors associated with OTC medication use for children. Result: Nearly half of the mothers reported administering OTC medications to their children. Factors associated with this practice included the child’s age (specifically 48–72 months), attendance at nursery, perceived underweight status, and regular health visits with a pediatrician. Additionally, mothers who frequently used medications without a doctor’s recommendation were 5.8 times more likely to give OTC drugs to their children. Maternal self-medication was significantly associated with an increased likelihood of OTC medication use for children (OR = 12.1). The most commonly used supplements included vitamin D, fish oil, multivitamins, vitamin C, immune boosters, zinc, probiotics, herbal teas, oral/nasal sprays, throat lozenges, and aspirin, with the primary purposes being prevention and treatment. Conclusions: The administration of OTC medications in young children, who rely heavily on maternal care should be more closely monitored to ensure their safety and well-being, especially during epidemics. Full article
(This article belongs to the Section Nutrition and Public Health)
24 pages, 1938 KiB  
Article
Orange Peel Lactiplantibacillus plantarum: Development of A Mucoadhesive Nasal Spray with Antimicrobial and Anti-inflammatory Activity
by Elisa Corazza, Asia Pizzi, Carola Parolin, Barbara Giordani, Angela Abruzzo, Federica Bigucci, Teresa Cerchiara, Barbara Luppi and Beatrice Vitali
Pharmaceutics 2024, 16(11), 1470; https://doi.org/10.3390/pharmaceutics16111470 - 18 Nov 2024
Cited by 1 | Viewed by 1778
Abstract
Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum [...] Read more.
Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum BIA was isolated from orange peel and taxonomically identified through 16S rRNA gene sequencing. Its antibacterial activity was tested against Pseudomonas aeruginosa, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, while anti-inflammatory potential was evaluated by Griess assay. BIA genome was fully sequenced and analyzed to assess its safety. BIA was formulated in a freeze-dried matrix, containing prebiotics and cryoprotectants, to be reconstituted with a polymer solution. Solutions containing two types of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid were evaluated as resuspending media and compared in terms of pH, viscosity, and mucoadhesion ability. The biological activity of BIA formulated as nasal spray was verified together with the stability of the selected formulations. Results: L. plantarum BIA inhibited human pathogens’ growth and showed anti-inflammatory activity and a safe profile. In the best-performing formulation, the probiotic is lyophilized in 10% fructooligosaccharides, 0.1% ascorbic acid, and 0.5% lactose and reconstituted with HPMC high viscosity 1% w/v. This composition ensured the probiotic’s viability for up to six months in its dried form and one week after reconstitution. It also allowed interaction with the nasal mucosa, preserving its antimicrobial and anti-inflammatory activities. Conclusion: The developed nasal spray could become a promising formulation in the field of nasal infectious and inflammatory diseases. Full article
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14 pages, 1945 KiB  
Article
Whole-Genome Deep Sequencing of the Healthy Adult Nasal Microbiome
by Mark Cannon, Gustavo Ferrer, Mari Tesch and Matthew Schipma
Microorganisms 2024, 12(7), 1407; https://doi.org/10.3390/microorganisms12071407 - 12 Jul 2024
Viewed by 3192
Abstract
This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential [...] Read more.
This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes”. Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness. Full article
(This article belongs to the Special Issue Bioinformatics and Omic Data Analysis in Microbial Research)
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12 pages, 2629 KiB  
Article
The Mucus-Binding Factor Mediates Lacticaseibacillus rhamnosus CRL1505 Adhesion but Not Immunomodulation in the Respiratory Tract
by Binghui Zhou, Mariano Elean, Lorena Arce, Kohtaro Fukuyama, Kae Tomotsune, Stefania Dentice Maidana, Sudeb Saha, Fu Namai, Keita Nishiyama, María Guadalupe Vizoso-Pinto, Julio Villena and Haruki Kitazawa
Microorganisms 2024, 12(6), 1209; https://doi.org/10.3390/microorganisms12061209 - 16 Jun 2024
Viewed by 1966
Abstract
Lacticaseibacillus rhamnosus CRL1505 possesses immunomodulatory activities in the gastrointestinal and respiratory tracts when administered orally. Its adhesion to the intestinal mucosa does not condition its beneficial effects. The intranasal administration of L. rhamnosus CRL1505 is more effective than the oral route at modulating [...] Read more.
Lacticaseibacillus rhamnosus CRL1505 possesses immunomodulatory activities in the gastrointestinal and respiratory tracts when administered orally. Its adhesion to the intestinal mucosa does not condition its beneficial effects. The intranasal administration of L. rhamnosus CRL1505 is more effective than the oral route at modulating immunity in the respiratory tract. Nonetheless, it has not yet been established whether the adherence of the CRL1505 strain to the respiratory mucosa is needed to provide the immune benefits to the host. In this study, we evaluated the role of adhesion to the respiratory mucosa of the mucus-binding factor (mbf) knock-out L. rhamnosus CRL1505 mutant (Δmbf CRL1505) in the context of a Toll-like receptor 3 (TLR3)-triggered innate immunity response. In vitro adhesion studies in porcine bronchial epitheliocytes (PBE cells) indicated that L. rhamnosus Δmbf CRL1505 adhered weakly compared to the wild-type strain. However, in vivo studies in mice demonstrated that the Δmbf CRL1505 also reduced lung damage and modulated cytokine production in the respiratory tract after the activation of TLR3 to a similar extent as the wild-type strain. In addition, the mutant and the wild-type strains modulated the production of cytokines and antiviral factors by alveolar macrophages in the same way. These results suggest that the Mbf protein is partially involved in the ability of L. rhamnosus CRL1505 to adhere to the respiratory epithelium, but the protein is not necessary for the CRL1505 strain to exert its immunomodulatory beneficial effects. These findings are a step forward in the understanding of molecular interactions that mediate the beneficial effects of nasally administered probiotics. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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16 pages, 1999 KiB  
Article
Immunobiotic Ligilactobacillus salivarius FFIG58 Confers Long-Term Protection against Streptococcus pneumoniae
by Mariano Elean, Fernanda Raya Tonetti, Kohtaro Fukuyama, Luciano Arellano-Arriagada, Fu Namai, Yoshihito Suda, Nadia Gobbato, Keita Nishiyama, Julio Villena and Haruki Kitazawa
Int. J. Mol. Sci. 2023, 24(21), 15773; https://doi.org/10.3390/ijms242115773 - 30 Oct 2023
Cited by 7 | Viewed by 2290
Abstract
Previously, we isolated potentially probiotic Ligilactobacillus salivarius strains from the intestines of wakame-fed pigs. The strains were characterized based on their ability to modulate the innate immune responses triggered by the activation of Toll-like receptor (TLR)-3 or TLR4 signaling pathways in intestinal mucosa. [...] Read more.
Previously, we isolated potentially probiotic Ligilactobacillus salivarius strains from the intestines of wakame-fed pigs. The strains were characterized based on their ability to modulate the innate immune responses triggered by the activation of Toll-like receptor (TLR)-3 or TLR4 signaling pathways in intestinal mucosa. In this work, we aimed to evaluate whether nasally administered L. salivarius strains are capable of modulating the innate immune response in the respiratory tract and conferring long-term protection against the respiratory pathogen Streptococcus pneumoniae. Infant mice (3-weeks-old) were nasally primed with L. salivarius strains and then stimulated with the TLR3 agonist poly(I:C). Five or thirty days after the last poly(I:C) administration mice were infected with pneumococci. Among the strains evaluated, L. salivarius FFIG58 had a remarkable ability to enhance the protection against the secondary pneumococcal infection by modulating the respiratory immune response. L. salivarius FFIG58 improved the ability of alveolar macrophages to produce interleukin (IL)-6, interferon (IFN)-γ, IFN-β, tumor necrosis factor (TNF)-α, IL-27, chemokine C-C motif ligand 2 (CCL2), chemokine C-X-C motif ligand 2 (CXCL2), and CXCL10 in response to pneumococcal challenge. Furthermore, results showed that the nasal priming of infant mice with the FFIG58 strain protected the animals against secondary infection until 30 days after stimulation with poly(I:C), raising the possibility of using nasally administered immunobiotics to stimulate trained immunity in the respiratory tract. Full article
(This article belongs to the Special Issue Molecular Research in Prebiotics, Probiotics and Postbiotics)
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31 pages, 4186 KiB  
Review
Understanding the Relationship of the Human Bacteriome with COVID-19 Severity and Recovery
by Hassan Zafar and Milton H. Saier
Cells 2023, 12(9), 1213; https://doi.org/10.3390/cells12091213 - 22 Apr 2023
Cited by 2 | Viewed by 5149
Abstract
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. Evidence has been provided that this novel virus originated in animals, mutated, and made the cross-species jump [...] Read more.
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. Evidence has been provided that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on its way to an endemic form; however, the threat of the virus is more for susceptible (older and immunocompromised) people. The human body has millions of bacterial cells that influence health and disease. As a consequence, the bacteriomes in the human body substantially influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. In major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. That have a positive effect on the functionality of the immune system and human health. These select bacterial spp. Could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. That could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacies. Full article
(This article belongs to the Collection Cellular Immunology and COVID-19)
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19 pages, 3263 KiB  
Article
Lacticaseibacillus paracasei GM-080 Ameliorates Allergic Airway Inflammation in Children with Allergic Rhinitis: From an Animal Model to a Double-Blind, Randomized, Placebo-Controlled Trial
by En-Kwang Lin, Wen-Wei Chang, Jhih-Hua Jhong, Wan-Hua Tsai, Chia-Hsuan Chou and I-Jen Wang
Cells 2023, 12(5), 768; https://doi.org/10.3390/cells12050768 - 28 Feb 2023
Cited by 22 | Viewed by 4428
Abstract
Background: Probiotics may facilitate the clinical management of allergic diseases. However, their effects on allergic rhinitis (AR) remain unclear. We examined the efficacy and safety of Lacticaseibacillus paracasei GM-080 in a mouse model of airway hyper-responsiveness (AHR) and in children with perennial AR [...] Read more.
Background: Probiotics may facilitate the clinical management of allergic diseases. However, their effects on allergic rhinitis (AR) remain unclear. We examined the efficacy and safety of Lacticaseibacillus paracasei GM-080 in a mouse model of airway hyper-responsiveness (AHR) and in children with perennial AR (PAR) by using a double-blind, prospective, randomized, placebo-controlled design. Methods: The production of interferon (IFN)-γ and interleukin (IL)-12 was measured by using an enzyme-linked immunosorbent assay. GM-080 safety was evaluated via the whole-genome sequencing (WGS) of virulence genes. An ovalbumin (OVA)-induced AHR mouse model was constructed, and lung inflammation was evaluated by measuring the infiltrating leukocyte content of bronchoalveolar lavage fluid. A clinical trial was conducted with 122 children with PAR who were randomized to receive different doses of GM-080 or the placebo for 3 months, and their AHR symptom severity scores, total nasal symptom scores (TNSSs), and Investigator Global Assessment Scale scores were examined. Results: Among the tested L. paracasei strains, GM-080 induced the highest IFN-γ and IL-12 levels in mouse splenocytes. WGS analysis revealed the absence of virulence factors or antibiotic-resistance genes in GM-080. The oral administration of GM-080 at 1 × 107 colony forming units (CFU)/mouse/day for 8 weeks alleviated OVA-induced AHR and reduced airway inflammation in mice. In children with PAR, the oral consumption of GM-080 at 2 × 109 CFU/day for 3 months ameliorated sneezing and improved Investigator Global Assessment Scale scores significantly. GM-080 consumption led to a nonsignificant decrease in TNSS and also nonsignificantly reduced IgE but increased INF-γ levels. Conclusion: GM-080 may be used as a nutrient supplement to alleviate airway allergic inflammation. Full article
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20 pages, 2259 KiB  
Article
Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification
by Carlo Brogna, Vincenzo Costanzo, Barbara Brogna, Domenico Rocco Bisaccia, Giancarlo Brogna, Marino Giuliano, Luigi Montano, Valentina Viduto, Simone Cristoni, Mark Fabrowski and Marina Piscopo
Int. J. Mol. Sci. 2023, 24(4), 3929; https://doi.org/10.3390/ijms24043929 - 15 Feb 2023
Cited by 21 | Viewed by 6920
Abstract
SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in [...] Read more.
SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients’ blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria. Full article
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16 pages, 3233 KiB  
Article
The Mucus Binding Factor Is Not Necessary for Lacticaseibacillus rhamnosus CRL1505 to Exert Its Immunomodulatory Activities in Local and Distal Mucosal Sites
by Kae Tomotsune, Fernanda Raya Tonetti, Hiroya Mizuno, Mariano Elean, Kohtaro Fukuyama, Binghui Zhou, Wakako Ikeda-Ohtsubo, Keita Nishiyama, Akihiro Yamamura, Hideaki Karasawa, Shinobu Ohnuma, Akira Horii, Tadao Saito, Haruki Kitazawa and Julio Villena
Int. J. Mol. Sci. 2022, 23(22), 14357; https://doi.org/10.3390/ijms232214357 - 18 Nov 2022
Cited by 4 | Viewed by 2468
Abstract
Both viable and non-viable orally administered Lacticaseibacillus rhamnosus CRL1505 modulate immunity in local (intestine) and distal (respiratory) mucosal sites. So, intestinal adhesion and colonization are not necessary for this probiotic strain to exert its immunomodulatory effects. In this work, a mucus-binding factor knockout [...] Read more.
Both viable and non-viable orally administered Lacticaseibacillus rhamnosus CRL1505 modulate immunity in local (intestine) and distal (respiratory) mucosal sites. So, intestinal adhesion and colonization are not necessary for this probiotic strain to exert its immunomodulatory effects. In this work, a mucus-binding factor knockout CRL1505 strain (ΔmbfCRL1505) was obtained and the lack of binding ability to both intestinal epithelial cells and mucin was demonstrated in vitro. In addition, two sets of in vivo experiments in 6-week-old Balb/c mice were performed to evaluate ΔmbfCRL1505 immunomodulatory activities. (A) Orally administered ΔmbfCRL1505 prior to intraperitoneal injection of the Toll-like receptor 3 (TLR3) agonist poly(I:C) significantly reduced intraepithelial lymphocytes (CD3+NK1.1+CD8αα+) and pro-inflammatory mediators (TNF-α, IL-6 and IL-15) in the intestinal mucosa. (B) Orally administered ΔmbfCRL1505 prior to nasal stimulation with poly(I:C) significantly decreased the levels of the biochemical markers of lung tissue damage. In addition, reduced recruitment of neutrophils and levels of pro-inflammatory mediators (TNF-α, IL-6 and IL-8) as well as increased IFN-β and IFN-γ in the respiratory mucosa were observed in ΔmbfCRL1505-treated mice when compared to untreated control mice. The immunological changes induced by the ΔmbfCRL1505 strain were not different from those observed for the wild-type CRL1505 strain. Although it is generally accepted that the expression of adhesion factors is necessary for immunobiotics to induce their beneficial effects, it was demonstrated here that the mbf protein is not required for L. rhamnosus CRL1505 to exert its immunomodulatory activities in local and distal mucosal sites. These results are a step forward towards understanding the mechanisms involved in the immunomodulatory capabilities of L. rhamnosus CRL1505. Full article
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8 pages, 780 KiB  
Review
A Brief Review of Local Bacteriotherapy for Preventing Respiratory Infections
by Giorgio Ciprandi, Valerio Damiani, Vittorio Cordara and Maria Angela Tosca
Allergies 2022, 2(4), 138-145; https://doi.org/10.3390/allergies2040013 - 7 Nov 2022
Cited by 1 | Viewed by 2546
Abstract
Recurrent respiratory infections (RRIs) account for relevant economic and social implications and significantly affect family life. Local Bacteriotherapy (LB) represents an innovative option in preventing RRIs. Local bacteriotherapy consists of administering “good” and safe bacteria (probiotics) by nasal or oral route. In particular, [...] Read more.
Recurrent respiratory infections (RRIs) account for relevant economic and social implications and significantly affect family life. Local Bacteriotherapy (LB) represents an innovative option in preventing RRIs. Local bacteriotherapy consists of administering “good” and safe bacteria (probiotics) by nasal or oral route. In particular, two strains (Streptococcus salivarius 24SMB and Streptococcus oralis 89a) are commonly used. The present article presents and discusses the literature concerning LB. Infections of airways include the upper and lower respiratory tract. A series of clinical trials investigated the preventive role of LB in preventing upper and lower RIs. These studies demonstrated that LB safely reduced the prevalence and severity of RIs, the use of antibiotics, and absences from school. Therefore, Local Bacteriotherapy may be considered an interesting therapeutic option in RRI prevention. Full article
(This article belongs to the Special Issue Probiotics in Allergy, Asthma and Respiratory Infections)
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