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Dezfouli KA, Darban M, Hemmati M, Zahir M, Kermanshahi MS, Abdolshahi A, Sadr H, Bagheri B. A Randomized, Controlled Study Evaluating Effects of Saccharomyces boulardii in Adult Patients with Asthma. Drug Res (Stuttg) 2025. [PMID: 40228543 DOI: 10.1055/a-2564-2569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
To determine the potential benefit of adding Saccharomyces boulardii (S. boulardii) probiotic supplementation to conventional treatments in asthmatic patients.In this randomized, double-blinded, and placebo-controlled trial 50 asthmatic patients were enrolled. The eligible subjects received either S. boulardii (N=25) or placebo (N=25) added to conventional treatments for three months. Spirometry parameters (FEV1, FVC, FEV1/FVC, and FEF 25-75%) and blood test parameters (CBC, eosinophil percentage, IgE, IL-5, ESR and CRP) were measured and compared at baseline and after treatment completion.The mean age was 39.22±12.55 years. As compared to baseline values, a significant improvement was noted in FEV1 in patients who received S. boulardii (p=0.026). Although the changes in FEV1, FVC, FEV1/FVC, and FEF 25-75% were comparable between the study groups, the differences were not statistically significant (p ˃ 0.05). In addition, patients who received probiotic showed lower levels of IL-5 and IgE in comparison with patients who received placebo.Our findings showed that the addition of S. boulardii to conventional treatments partially improved the pulmonary function and was associated with reductions in IgE and IL-5 levels.
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Affiliation(s)
- Kavosh Ansari Dezfouli
- Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
- Department of Internal Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mahboubeh Darban
- Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Maral Hemmati
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Mazyar Zahir
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Anna Abdolshahi
- Food Safety Research Center (salt), Semnan University of Medical Sciences, Semnan, Iran
| | - Hani Sadr
- Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Bahador Bagheri
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland
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Xi Z, Fenglin X, Yun Z, Chunrong L. Efficacy of probiotics in the treatment of allergic diseases: a meta-analysis. Front Nutr 2025; 12:1502390. [PMID: 40104820 PMCID: PMC11913692 DOI: 10.3389/fnut.2025.1502390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 02/12/2025] [Indexed: 03/20/2025] Open
Abstract
Background information Allergic diseases are an increasingly serious health issue worldwide, affecting not only the physiological health of patients but also significantly reducing their quality of life, thereby imposing a substantial economic burden on families and society. According to data from the World Health Organization, the incidence of allergic diseases has risen markedly over the past few decades, particularly among children and adolescents, making it a significant public health challenge. Although several clinical studies have explored the effects of probiotics in the treatment of food-induced allergies and allergic diseases, the results have been inconsistent. Some studies indicate positive effects, while others fail to demonstrate their efficacy. Therefore, a systematic evaluation of the effectiveness of probiotics in allergic diseases is particularly important. Some studies indicate that patients with food allergies may also experience respiratory symptoms, and certain foods may be associated with the onset or exacerbation of allergic rhinitis and asthma. Diseases such as allergic rhinitis, asthma, and atopic dermatitis are characterized by inappropriate immune responses to typically harmless environmental allergens. The incidence of these diseases is continuously rising in urban populations, prompting researchers to extensively explore novel therapeutic strategies that can effectively modulate immune responses. Objective The aim of this study is to systematically assess the effectiveness of probiotics in the treatment of allergic diseases. By integrating the results of existing clinical studies, we hope to provide a clearer scientific basis for the treatment of allergic diseases. Methods We conducted a comprehensive literature search in databases such as PubMed for articles published before the end of 2023 that evaluated the effectiveness of probiotics in treating allergic diseases. Inclusion criteria focused on studies reporting binary outcomes related to the efficacy of probiotics in patients with food allergies, asthma, allergic rhinitis, or atopic dermatitis. Data were collected using Excel software, and the Review Manager software was used to analyze the collected binary variable data. The effectiveness of probiotics was assessed by calculating the risk ratio (RR) and its 95% confidence interval (CI). Heterogeneity among studies was evaluated using the I2 statistic, and publication bias was assessed through funnel plots. Results The analysis of the aggregated binary data indicates that probiotics significantly improve clinical outcomes in patients with allergic diseases. Additional analysis using continuous variables (scores) further demonstrates the effectiveness of probiotics in alleviating allergic diseases. Subgroup analyses show that probiotics are effective in treating various common conditions, with two specific probiotics strains being particularly effective for allergic diseases. Conclusion We included literature involving pediatric patients with common allergic diseases, Probiotics can help treat allergic diseases by modulating immune mechanisms, but allergic diseases are typically caused by multiple factors and individual variations, however, allergic diseases are typically caused by multiple factors and individual variations, so they should not be used as the sole treatment method.This meta-analysis provides evidence supporting the effectiveness of probiotics in various allergic diseases. The findings suggest that probiotics can serve as a beneficial adjunctive therapy for the treatment of these conditions. Systematic review registration https://clinicaltrials.gov/, CRD42024586317.
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Affiliation(s)
- Zhang Xi
- Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xing Fenglin
- Chengdu Qingyang District Maternal and Child Health Hospital, Chengdu, China
| | - Zhao Yun
- Chengdu Children's Specialized Hospital, Chengdu, China
| | - Li Chunrong
- Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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Tafrishi R, Ahanchian H, Jafari SA, Pahlevanloo A, Kianifar H, Kiani M, Moazzen N, sadeghi T, Sly PD. Development and clinical assessment of a novel probiotic candy in the prevention of respiratory infections in asthmatic children. World Allergy Organ J 2025; 18:101023. [PMID: 39906528 PMCID: PMC11791275 DOI: 10.1016/j.waojou.2024.101023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 11/25/2024] [Accepted: 12/13/2024] [Indexed: 02/06/2025] Open
Abstract
Objective Asthma is the most common chronic disease among children. Upper respiratory infections are often the cause of asthma exacerbation. Studies suggested that spore-forming probiotics can reduce viral infections. This study aimed to determine the effect of spore-forming probiotic Bacillus candy on respiratory illnesses in asthmatic children. Methods & materials In this randomized trial, 69 children aged 7-11 years with mild intermittent asthma were randomized to receive probiotic candy (containing 1010 CFU probiotic Bacillus coagulans) or placebo candy, daily for 2 months. The primary outcome was the number of viral respiratory infections. Secondary outcomes included salbutamol metered-dose inhaler (MDI) use, oral corticosteroids, school absenteeism, emergency department visits and hospitalizations, and Pediatric Asthma Control Questionnaire (c-ACT). Results The frequency of symptomatic respiratory illnesses was significantly lower in the probiotic candy group compared to placebo in the first month (0.28 ± 0.45 vs. 0.51 ± 0.50, p = 0.054), the second month (0.08 ± 0.28 vs. 0.41 ± 0.49, p = 0.001) and the total study (0.37 ± 0.54 vs. 0.90 ± 0.73, 0.001). The percent of patients with prednisolone consumption in the probiotic group was lower than the control group (2.9% vs. 14.7%) but did not show a significant difference (p = 0.081) and no difference was seen in the rate of emergency department visits and hospitalization between the 2 groups (both p = 0.254). The use of salbutamol and school absenteeism in the probiotic group was significantly lower than in the control group (p = 0.040 and p = 0.046, respectively. There was no significant difference in the evaluated scores for asthma control (c-ACT) in both probiotic and placebo groups. After the intervention, the difference between the 2 groups has become significant (p < 0.05). Conclusion Adding spore-forming probiotic candy containing Bacillus coagulans to standard asthma treatments reduced symptomatic respiratory illnesses over two months. Further studies including longer treatment periods are needed before making recommendations for routine use.
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Affiliation(s)
- Rana Tafrishi
- Department of Allergy and Immunology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Ahanchian
- Child Health Research Centre, University of Queensland, South Brisbane, Australia
- Allergy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed ali Jafari
- Pediatrics Gastroenterology Department, Akbar Children Hospital, Mashhad University of Medical Sciences, Iran
| | - Abolfazl Pahlevanloo
- Food Biotechnology, Department of Food Biotechnology, Research Institute of Food Science and Technology, Mashhad, Iran
| | - Hamidreza Kianifar
- Pediatrics Gastroenterology Department, Akbar Children Hospital, Mashhad University of Medical Sciences, Iran
| | - Mohammadali Kiani
- Pediatrics Gastroenterology Department, Akbar Children Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nasrin Moazzen
- Allergy and Clinical Immunology, Department of Pediatrics, School of Medicine, Akbar Children Hospital, Mashhad University of Medical Sciences, Iran
| | - Tahereh sadeghi
- Nursing and Midwifery Care Research Center, Akbar Children Hospital, Mashhad University of Medical Sciences, Iran
| | - Peter D. Sly
- Child Health Research Centre, University of Queensland, South Brisbane, Australia
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Rathi A, Khaire RA, Rathi VL. A Prospective, Interventional, Randomized, Double-Blinded, Placebo-Controlled, Monocentric Clinical Study to Evaluate the Efficacy and Safety of Alkalihalobacillus clausii 088AE in Resolution of Acute Allergic Rhinitis Symptoms. GLOBAL ADVANCES IN INTEGRATIVE MEDICINE AND HEALTH 2025; 14:27536130251321821. [PMID: 40092216 PMCID: PMC11909684 DOI: 10.1177/27536130251321821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/23/2025] [Accepted: 02/03/2025] [Indexed: 03/19/2025]
Abstract
Background Allergic rhinitis (AR) is a common inflammatory disease of the upper respiratory tract mainly triggered by allergens such as dust mites, pollen, spores, and viral or bacterial infections. AR is primarily associated with symptoms such as nasal itching, sneezing, rhinorrhea, nasal congestion, and watery, itchy, or red eyes. AR significantly affects an individual's quality of life. Probiotics have been proven effective in the clinical management of AR through immunomodulation. However, studies on the use of Alkalihalobacillus clausii to alleviate the symptoms of AR have rarely been reported. Objective This study aimed to explore the clinical efficacy, safety, and possible underlying mechanism of Alkalihalobacillus clausii 088AE in alleviating the associated symptoms of acute AR in patients. Methods A prospective, interventional, randomized, double-blinded, placebo-controlled, monocentric clinical study was conducted on patients with acute AR (N = 40) randomized into two groups, test (N = 20) and placebo (N = 20). Patients in the test arm received a probiotic strain, A. clausii 088AE, whereas patients in the placebo arm received Maltodextrin. The primary endpoints (efficacy) were total 4 nasal symptoms scores (T4NSS), total 2 ocular symptoms scores (T2OSS), cough scores, and immunological parameters (T-helper 1 (Th1), Th2, Th17, and T-regulatory (Treg) cells, Interleukin (IL)-4, IL10, IL17, IL22, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and -beta (TNF-β), and forkhead box P3 (FOXP3)) evaluated from baseline to end of treatment (EOT). The secondary endpoints (safety) assessed were vital physical signs, hematology, and biochemical parameters, along with an assessment of adverse or serious adverse events (AEs and SAEs). Results A. clausii 088AE supplementation significantly reduced the T4NSS (rhinorrhoea, nasal stuffiness, nasal itching, and sneezing; P < 0.001), T2OSS (itching and watery eyes; P < 0.001), and cough scores (P < 0.01) by the EOT compared to baseline. The placebo group reported a significant increase in all the above symptom scores at the EOT from their baseline values (P < 0.001). The intergroup analysis between A. clausii 088AE and placebo indicated a significant change in T4NSS, T2OSS, and cough score (P < 0.001). Further, the immunological parameters were improved (non-significant, P-value ≥ 0.05) with the probiotic supplementation. No adverse events (AEs) or serious adverse events (SAEs) leading to termination of study participation were reported with the use of A. clausii 088AE in the study. No clinically significant vital signs and physical examinations were reported as AEs or SAEs by the investigator. Conclusion A. clausii 088AE supplementation improved the clinical symptoms in patients with AR. At the administered oral dose, A. clausii 088AE was found to be safe and tolerable in adult subjects with acute allergic rhinitis. A. clausii 088AE can be recommended to support the clinical pathophysiology of AR-related symptoms of the host. Besides, clinical studies with a larger population, multiple centres, and prolonged intervention periods are necessary to validate the significance of this study further.
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Affiliation(s)
- Abhijit Rathi
- Human Nutrition Department, Advanced Enzymes Technologies Ltd, Thane, India
| | | | - V. L. Rathi
- Human Nutrition Department, Advanced Enzymes Technologies Ltd, Thane, India
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Daglia M, Drago L, Ullah H, Di Minno A, Brindisi G, Brunese FP, Dinardo G, Gori A, Indolfi C, Naso M, Tondina E, Trincianti C, Varricchio A, Zicari AM, Ciprandi G. Effects of the supplementation of single and multi-strain probiotics, alone or in combination with other treatments, on asthma in children: A systematic review of the randomized, placebo-controlled clinical studies. J Funct Foods 2024; 123:106599. [DOI: 10.1016/j.jff.2024.106599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
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Balan D, Baral T, Manu MK, Mohapatra AK, Miraj SS. Efficacy of probiotics as adjuvant therapy in bronchial asthma: a systematic review and meta-analysis. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2024; 20:60. [PMID: 39563347 PMCID: PMC11575415 DOI: 10.1186/s13223-024-00922-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 10/31/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Asthma is a chronic, heterogeneous disease characterized by airway inflammation. Asthma exacerbations significantly increase the disease burden, necessitating new therapeutic approaches. Emerging evidence suggests probiotics, through the gut-lung axis, may benefit asthma management by modulating immune responses and reducing inflammation. METHODS This systematic review and meta-analysis adhered to PRISMA guidelines and was registered with PROSPERO (CRD42023480098). A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted up to March 2024. Inclusion criteria encompassed randomized controlled trials (RCTs) evaluating probiotic interventions in asthma patients. Statistical analysis was done using RevMan 5.3, with odds ratios (OR) and 95% confidence intervals (CI) calculated, and heterogeneity assessed using I2 statistics. RESULTS Twelve RCTs, comprising 1401 participants, met the inclusion criteria. The probiotic strains investigated included various Lactobacillus and Bifidobacterium species. Meta-analysis revealed significant improvements in asthma control test scores (OR 1.18, 95% CI: 1.18-3.64, p = 0.0001) following probiotic supplementation. Probiotics also improved fractional exhaled nitric oxide (FeNO) in one study, but pooled FeNO and eosinophil data were not statistically significant (p = 0.46 and p = 0.29, respectively). One study observed fewer asthma exacerbations in the probiotic group (24/212) compared to placebo (67/210), with no difference in exacerbation duration. CONCLUSION Probiotic supplementation may be beneficial in improving asthma symptom control with no significant impact on lung function indices or eosinophil levels. Probiotics can be a potential adjunctive therapy in asthma management, particularly for asthma symptom control.
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Affiliation(s)
- Divya Balan
- Department of Respiratory Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Tejaswini Baral
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Mohan K Manu
- Department of Respiratory Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
| | - Aswini Kumar Mohapatra
- Department of Respiratory Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Sonal Sekhar Miraj
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
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Luo X, Wang H, Liu H, Chen Y, Tian L, Ji Q, Xie D. Effects of probiotics on the prevention and treatment of children with allergic rhinitis: a meta-analysis of randomized controlled trials. Front Pediatr 2024; 12:1352879. [PMID: 39421038 PMCID: PMC11484092 DOI: 10.3389/fped.2024.1352879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 07/30/2024] [Indexed: 10/19/2024] Open
Abstract
Background and aim Recent studies have demonstrated the anti-allergic effects of probiotics in humans. However, their role in preventing and treating pediatric allergic rhinitis has not been thoroughly investigated. This study aimed to systematically review the efficacy and preventive effects of probiotics on pediatric allergic rhinitis. Methods We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases for all relevant studies on probiotics and pediatric allergic rhinitis. Studies meeting the inclusion criteria were included, data were extracted, and meta-analyses were performed. Results A total of 28 studies with 4,765 participants were included in this study. The pooled results showed that the use of probiotics was associated with a significant improvement in total nose symptom scores (SMD, -2.27; 95% CI, -3.26 to -1.29; P < 0.00001), itchy nose scores (SMD, -0.44; 95% CI, -0.80 to -0.07; P = 0.02), sneezing scores (SMD, -0.47; 95% CI, -0.84 to -0.10; P = 0.01), eye symptoms (SMD, -3.77; 95% CI, -5.47 to -2.07; P < 0.00001), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (SMD, -2.52; 95% CI, -4.12 to -0.92; P < 00001). However, the use of probiotics was not associated with the incidence of allergic rhinitis (RR, 0.9; 95% CI, 0.74-1.08; P = 0.26). Conclusions The present study demonstrated that probiotics were effective and safe for improving pediatric allergic rhinitis symptoms and quality of life. However, probiotics could not prevent pediatric allergic rhinitis.
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Affiliation(s)
- Xinyi Luo
- The First Affiliated Hospital of Chengdu Medical College Clinical Medical College, Chengdu, Sichuan, China
| | - Huan Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Huixia Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yue Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Li Tian
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qing Ji
- Department of Otolaryngology, Chengdu First People’s Hospital, Chengdu, Sichuan, China
| | - Dengpiao Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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Nasreen S, Ali S, Andleeb S, Summer M, Hussain T, Imdad K, Ara C, Tahir HM. Mechanisms of medicinal, pharmaceutical, and immunomodulatory action of probiotics bacteria and their secondary metabolites against disease management: an overview. Folia Microbiol (Praha) 2024; 69:549-565. [PMID: 38532057 DOI: 10.1007/s12223-024-01155-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 03/05/2024] [Indexed: 03/28/2024]
Abstract
Probiotics or bacteriotherapy is today's hot issue for public entities (Food and Agriculture Organization, and World Health Organization) as well as health and food industries since Metchnikoff and his colleagues hypothesized the correlation between probiotic consumption and human's health. They contribute to the newest and highly efficient arena of promising biotherapeutics. These are usually attractive in biomedical applications such as gut-related diseases like irritable bowel disease, diarrhea, gastrointestinal disorders, fungal infections, various allergies, parasitic and bacterial infections, viral diseases, and intestinal inflammation, and are also worth immunomodulation. The useful impact of probiotics is not limited to gut-related diseases alone. Still, these have proven benefits in various acute and chronic infectious diseases, like cancer, human immunodeficiency virus (HIV) diseases, and high serum cholesterol. Recently, different researchers have paid special attention to investigating biomedical applications of probiotics, but consolidated data regarding bacteriotherapy with a detailed mechanistically applied approach is scarce and controversial. The present article reviews the bio-interface of probiotic strains, mainly (i) why the demand for probiotics?, (ii) the current status of probiotics, (iii) an alternative to antibiotics, (iv) the potential applications towards disease management, (v) probiotics and industrialization, and (vi) futuristic approach.
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Affiliation(s)
- Sundas Nasreen
- Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan
| | - Shaukat Ali
- Department of Zoology, Government College University, Lahore, 54000, Pakistan.
| | - Saiqa Andleeb
- Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan
| | - Muhammad Summer
- Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Tauqeer Hussain
- Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Kaleem Imdad
- Department of Bioscience, COMSATS Institute of Information Technology (CIIT), Islamabad, 45550, Pakistan
| | - Chaman Ara
- Institute of Zoology, University of the Punjab, Lahore, Pakistan
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Xu X, Yin J, Yang Y, Liu H, Yu J, Luo X, Zhang Y, Song X. Advances in co-pathogenesis of the united airway diseases. Respir Med 2024; 225:107580. [PMID: 38484897 DOI: 10.1016/j.rmed.2024.107580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 02/02/2024] [Accepted: 02/22/2024] [Indexed: 03/19/2024]
Abstract
According to the concept of "united airway diseases", the airway is a single organ in which upper and lower airway diseases are commonly comorbid. A range of inflammatory factors have been found to play an important role in the chain reaction of upper and lower airway diseases. However, the amount of research on this concept remains limited. The underlying mechanism of the relationship between typical diseases of the united airway, such as asthma, allergic rhinitis, and chronic sinusitis, also needs to be further explored. This review highlights the interaction between upper and lower respiratory diseases gathered from epidemiological, histoembryology, neural mechanistic, microbiological, and clinical studies, revealing the relationship between the upper and lower respiratory tracts.
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Affiliation(s)
- Xinjun Xu
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Jiali Yin
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Yujuan Yang
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Huifang Liu
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China; The 2nd School of Clinical Medicine of Binzhou Medical University, Yantai, Shandong, China
| | - Jingyi Yu
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Xianghuang Luo
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China; School of Clinical Medicine, Weifang Medical University, Weifang, 261042, China
| | - Yu Zhang
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China.
| | - Xicheng Song
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China.
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Vijayan S, Kandi V, Palacholla PS, Rajendran R, Jarugu C, Ca J, Pravallika M, Reddy SC, Sucharitha AS. Probiotics in Allergy and Immunological Diseases: A Comprehensive Review. Cureus 2024; 16:e55817. [PMID: 38590477 PMCID: PMC10999892 DOI: 10.7759/cureus.55817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2024] [Indexed: 04/10/2024] Open
Abstract
Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life of individuals suffering from such diseases is crucial to tackling these diseases, especially through diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases is a hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appear to be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.
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Affiliation(s)
- Swapna Vijayan
- Pediatrics, Sir Chandrasekhara Venkata (CV) Raman General Hospital, Bangalore, IND
| | - Venkataramana Kandi
- Clinical Microbiology, Prathima Institute of Medical Sciences, Karimnagar, IND
| | - Pratyusha S Palacholla
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
| | | | - Chandrasagar Jarugu
- General Practice, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
| | - Jayashankar Ca
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
| | - Mundla Pravallika
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
| | - Shruthi C Reddy
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
| | - Atul S Sucharitha
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
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Virk MS, Virk MA, He Y, Tufail T, Gul M, Qayum A, Rehman A, Rashid A, Ekumah JN, Han X, Wang J, Ren X. The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs. Nutrients 2024; 16:546. [PMID: 38398870 PMCID: PMC10893534 DOI: 10.3390/nu16040546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/10/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024] Open
Abstract
Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.
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Affiliation(s)
- Muhammad Safiullah Virk
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | | | - Yufeng He
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Tabussam Tufail
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
- University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore 54000, Pakistan
| | - Mehak Gul
- Department of Internal Medicine, Sheikh Zayed Hospital, Lahore 54000, Pakistan
| | - Abdul Qayum
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Abdur Rehman
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Arif Rashid
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - John-Nelson Ekumah
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Xu Han
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Junxia Wang
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Xiaofeng Ren
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang 212013, China
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12
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Guo Z, Huang L, Lai S. Global knowledge mapping and emerging research trends in the microbiome and asthma: A bibliometric and visualized analysis using VOSviewer and CiteSpace. Heliyon 2024; 10:e24528. [PMID: 38304829 PMCID: PMC10831755 DOI: 10.1016/j.heliyon.2024.e24528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 01/10/2024] [Accepted: 01/10/2024] [Indexed: 02/03/2024] Open
Abstract
Background Numerous prior studies have extensively highlighted the significance of the microbiome in association with asthma. While several studies have concentrated on the asthma microbiome in previous research, there is currently a lack of publications that employ bibliometric methods to assess this area. Methods In this study, the Web of Science Core Collection database was utilized as the data source, and the SCI-EXPANDED index was employed to ensure that the retrieved data were comprehensive and accurate. All original research articles and review articles related to the correlation between asthma and the microbiome were systematically searched from the inception of the database until June 20, 2023. These articles were subsequently visualized and analyzed using VOSviewer and CiteSpace software. Results A total of 1366 relevant publications were acquired, indicating a consistent annual increase in global publications in the field. The United States and China emerged as the top two contributors to international publications. Among prolific authors, Susan V. Lynch achieved the highest publication record, with Hans Bisgaard and Jakob Stokholm sharing the second position. The majority of publications concentrated on allergy-related and microbiome areas, with a few comprehensive journals standing out. Journals with 40 or more publications included the Journal of Allergy and Clinical Immunology, Allergy, Frontiers in Immunology, and PLOS One. The top 5 cited journals were the Journal of Allergy and Clinical Immunology, PLOS One, American Journal of Respiratory and Critical Care Medicine, Clinical and Experimental Allergy, and Nature. Upon analyzing keywords, high-frequency terms, such as asthma, gut microbiota, microbiome, children, childhood asthma, allergy, risk, exposure, inflammation, diversity, and chain fatty acids emerged as representative terms in the field. Conclusion This study systematically presented a comprehensive overview of the literature regarding the association between asthma and the microbiome over the last two decades. Through a bibliometric perspective, the findings may assist researchers with a better understanding of the essential information in the field.
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Affiliation(s)
- ZhiFeng Guo
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China
| | - LingHong Huang
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China
| | - SuMei Lai
- Stem Cell Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China
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Lee YJ, Son SE, Im DS. Free fatty acid 3 receptor agonist AR420626 reduces allergic responses in asthma and eczema in mice. Int Immunopharmacol 2024; 127:111428. [PMID: 38159551 DOI: 10.1016/j.intimp.2023.111428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 12/15/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024]
Abstract
Free fatty acid 3 receptor (FFA3; previously GPR41) is a G protein-coupled receptor that senses short-chain fatty acids and dietary metabolites produced by the gut microbiota. FFA3 deficiency reportedly exacerbates inflammatory events in asthma. Herein, we aimed to determine the therapeutic potential of FFA3 agonists in treating inflammatory diseases. We investigated the effects of N-(2,5-dichlorophenyl)-4-(furan-2-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide (AR420626), an FFA3 agonist, in in vivo models of chemically induced allergic asthma and eczema in BALB/c mice. Administration of AR420626 decreased the number of immune cells in the bronchoalveolar lavage fluid and skin. AR420626 suppressed inflammatory cytokine expression in the lung and skin tissues. Histological examination revealed that AR420626 suppressed inflammation in the lungs and skin. Treatment with AR420626 significantly suppressed the enhanced lymph node size and inflammatory cytokine levels. Overall, FFA3 agonist AR420626 could suppress allergic asthma and eczema, implying that activation of FFA3 might be a therapeutic target for allergic diseases.
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Affiliation(s)
- Ye-Ji Lee
- Department of Biomedical and Pharmaceutical Sciences, Seoul 02446, Republic of Korea
| | - So-Eun Son
- Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea
| | - Dong-Soon Im
- Department of Biomedical and Pharmaceutical Sciences, Seoul 02446, Republic of Korea; Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea.
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14
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Kadia BM, Allen SJ. Effect of Pre-, Pro-, and Synbiotics on Biomarkers of Systemic Inflammation in Children: A Scoping Review. Nutrients 2024; 16:336. [PMID: 38337621 PMCID: PMC10856957 DOI: 10.3390/nu16030336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/19/2024] [Accepted: 01/19/2024] [Indexed: 02/12/2024] Open
Abstract
Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for the anti-inflammatory effects of pre-, pro-, and synbiotics in children. Of the 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 to September 2022, 29 were included in the review. In six studies of healthy children (n = 1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers, and one study of a single-strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain studies, one multi-strain probiotic, and one synbiotic study. In 23 studies of children with diseases (n = 1550), prebiotics were tested in 3, single-strain in 16, multi-strain probiotics in 6, and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of autoimmune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness, and 2/3 studies of other diseases. However, only one or two of several biomarkers were often improved; increased pro-inflammatory biomarkers occurred in five of these studies, and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro-, and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro-, and synbiotic preparations, health status, and biomarkers studied.
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Affiliation(s)
| | - Stephen John Allen
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK;
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Hua JL, Yang ZF, Cheng QJ, Han YP, Li ZT, Dai RR, He BF, Wu YX, Zhang J. Prevention of exacerbation in patients with moderate-to-very severe COPD with the intent to modulate respiratory microbiome: a pilot prospective, multi-center, randomized controlled trial. Front Med (Lausanne) 2024; 10:1265544. [PMID: 38249987 PMCID: PMC10797043 DOI: 10.3389/fmed.2023.1265544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 12/18/2023] [Indexed: 01/23/2024] Open
Abstract
Introduction Considering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza-Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD. Methods In this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5-7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza-S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months. Results Among all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD. Conclusion The influenza-S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03449459.
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Affiliation(s)
- Jian-lan Hua
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zi-feng Yang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Qi-jian Cheng
- Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yao-pin Han
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zheng-tu Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Ran-ran Dai
- Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin-feng He
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi-xing Wu
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jing Zhang
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, China
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16
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Hu M, Zhao X, Liu Y, Zhou H, You Y, Xue Z. Complex interplay of gut microbiota between obesity and asthma in children. Front Microbiol 2023; 14:1264356. [PMID: 38029078 PMCID: PMC10655108 DOI: 10.3389/fmicb.2023.1264356] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Obesity is an important risk factor and common comorbidity of childhood asthma. Simultaneously, obesity-related asthma, a distinct asthma phenotype, has attracted significant attention owing to its association with more severe clinical manifestations, poorer disease control, and reduced quality of life. The establishment of the gut microbiota during early life is essential for maintaining metabolic balance and fostering the development of the immune system in children. Microbial dysbiosis influences host lipid metabolism, triggers chronic low-grade inflammation, and affects immune responses. It is intimately linked to the susceptibility to childhood obesity and asthma and plays a potentially crucial transitional role in the progression of obesity-related asthma. This review article summarizes the latest research on the interplay between asthma and obesity, with a particular focus on the mediating role of gut microbiota in the pathogenesis of obesity-related asthma. This study aims to provide valuable insight to enhance our understanding of this condition and offer preliminary evidence to support the development of therapeutic interventions.
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Affiliation(s)
| | | | | | | | - Yannan You
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zheng Xue
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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17
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Lee JY, Kang JH, Jung YR, Kang CH. Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272 and MG4577 Modulate Allergic Inflammatory Response in RAW 264.7 and RBL-2H3 cells. Probiotics Antimicrob Proteins 2023; 15:1092-1101. [PMID: 35639267 PMCID: PMC9153226 DOI: 10.1007/s12602-022-09950-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2022] [Indexed: 12/12/2022]
Abstract
Allergic inflammation refers to a hyperimmune reaction that causes hypersensitivity responses such as hives, itchiness, runny nose, and cough due to specific allergens. Allergic diseases are known to be influenced by the diversity and distribution of intestinal microbiota, and Lactobacill is known to relieve allergic symptoms by modulating cytokines secreted by T helper type 1 (Th1)/Th2 cells. This study was designed to investigate the effects of Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272, MG4577, and MG4657 on levels of pro-inflammatory cytokines and proteins associated with allergic symptoms in RAW 264.7 macrophages, and RBL-2H3 mast cells, as well as their probiotic properties. MG4247, MG4272, and MG4577 significantly reduced tumor necrosis factor-α and interleukin (IL)-6 levels in LPS-induced RAW 264.7 macrophages, and markedly decreased IL-4, IL-5, and IL-13 levels and STAT6 phosphorylation in DNP-IgE/HSA sensitized RBL-2H3 mast cells. Furthermore, MG4247, MG4272, and MG4577 tolerated the acidic condition with pepsin and basic condition with bile salt, and showed a high adhesion rate (≥ 73.9%). In safety evaluation, MG4247, MG4272, and MG4577 showed no hemolytic or bile salt hydrolase activity and no cytotoxicity to HT-29 cells (≥ 96.7%). Hence, MG4272, MG4272, and MG4577 can be used as candidate probiotic strains to relieve cytokines associated with allergic inflammation.
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Affiliation(s)
- Ji Yeon Lee
- MEDIOGEN, Co., Ltd, Biovalley 1-ro, Jecheon-si, 27159, Republic of Korea
| | - Ju-Hui Kang
- Department of Applied Life Sciences, Graduate School, Konkuk University, BK21 Program, Chungju, 27478, Republic of Korea
| | - Ye-Rin Jung
- Department of Applied Life Sciences, Graduate School, Konkuk University, BK21 Program, Chungju, 27478, Republic of Korea
| | - Chang-Ho Kang
- MEDIOGEN, Co., Ltd, Biovalley 1-ro, Jecheon-si, 27159, Republic of Korea.
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18
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Xie Q, Yuan J, Wang Y. Treating asthma patients with probiotics: a systematic review and meta-analysis. NUTR HOSP 2023; 40:829-838. [PMID: 37073761 DOI: 10.20960/nh.04360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023] Open
Abstract
Introduction Objective: To evaluate the role of probiotics in the treatment of asthma patients by meta-analysis. Methods: PubMed, Embase, The Cochrane Library, Web of Science, and other databases were searched by computer, and the relevant literature on the treatment of asthma by probiotics that met the inclusion criteria was screened by manual retrieval. Meta-analysis was performed using Revman 5.4 software and the combined effect was evaluated by odds ratio (OR) or mean difference (MD) and 95 % confidence interval (CI). Results: a total of ten references were included, all of which were randomized controlled studies, and a total of 1,101 people were investigated. Fractional exhaled nitric oxide (FeNO) (MD = -7.17, 95 % CI: -12.81, -1.54), asthma symptom severity (MD = -0.07, 95 % CI: -0.10, -0.04), Childhood Asthma Control Test (CACT) (MD = 2.26, 95 % CI: 1.14, 3.39), and the number of acute episodes of asthma (OR = 0.30, 95 % CI: 0.19, 0.47) in the probiotics group were better than those in the control group. There was no significant difference in forced expiratory volume in the first second (FEV1) (MD = 0.11, 95 % CI: -0.05, 0.26) and FEV1/FVC (%) (MD = 0.32, 95 % CI: -1.48, 2.12). Conclusion: the use of probiotics in patients with asthma can improve lung inflammation and asthma symptoms, reduce the number of asthma attacks, and have no effect on lung function.
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Affiliation(s)
- Qiwei Xie
- The Affiliated Hospital of Medical School. Ningbo University
| | - Jiatian Yuan
- The Affiliated Hospital of Medical School. Ningbo University
| | - Yaoweng Wang
- The Affiliated Hospital of Medical School. Ningbo University
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19
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Liu D, Wang X, Zhang H. Efficacy and safety of gastrointestinal microbiome supplementation for allergic rhinitis: A systematic review and meta-analysis with trial sequential analysis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 118:154948. [PMID: 37418839 DOI: 10.1016/j.phymed.2023.154948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/07/2023] [Accepted: 07/01/2023] [Indexed: 07/09/2023]
Abstract
BACKGROUND Allergic rhinitis (AR) is a non-infective chronic inflammatory disease of nasal mucosa. PURPOSE To evaluate the efficacy and safety of gastrointestinal microbiome supplementation (GMS) for patients with allergic rhinitis (AR), concerning improvement on symptoms and signs, laboratory outcomes, quality of life, and medication scores. METHODS Five English databases were searched up to Dec 12th, 2022. Probiotics, prebiotics, and synbiotics were main therapies or adjuvants in experimental groups. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.4 Software, with meta-influence analyses, subgroup-analyses, meta-regression, and publication bias performed for exploration of heterogeneity by Stata V.14. Trial sequential analyses were performed by TSA 0.9, and quality of the results was accessed through the GRADE-pro GDT. RESULTS Finally, extracted from 53 articles, 65 RCTs involving 3,634 participants with sound worldwide representativeness were included. Primary results showed better improvement in GMS groups on TNSS (WMD=1.05, P for WMD=0.004, 95%CI:0.34 to 1.76), overall nasal condition (WMD=1.25, P for WMD<0.001, 95%CI:0.90 to 1.61), overall quality of life (WMD=6.16, P for WMD<0.001, 95%CI:4.92 to 7.40) and medication score (WMD=0.42, P for WMD=0.42, 95%CI:-0.06 to 0.90).However, GMS groups were inferior than the controls concerning reduction on serum total IgE (WMD=-1.81) and ratios of serum Th1/Th2 (WMD=-1.06). Meta-regressions suggested significant (p<0.05) variations of the effects in some comparisons. In addition, results of sub-group analyses firstly revealed potential influence between final results and the variables above. Instantly after intervention, the GRADE levels of evidence were sound, including "High ⨁⨁⨁⨁" in 10, "Moderate ⨁⨁⨁◯" in 33, and "Low ⨁⨁◯◯" in nine comparisons. However, overall certainties decreased obviously during follow-ups. CONCLUSION Overall, our pooled results firstly revealed that GMS yielded acceptable benefits for patients with AR compared with controls with sound certainties, after balancing the benefits and harms.
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Affiliation(s)
- Dongliang Liu
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, PR China
| | - Xilu Wang
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, PR China
| | - Hang Zhang
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, PR China.
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Wenger NM, Qiao L, Nicola T, Nizami Z, Martin I, Halloran BA, Tanaka K, Evans M, Xu X, Dinan TG, Kakilla C, DunnGalvin G, Ambalavanan N, Willis KA, Gaggar A, Lal CV. Clinical trial of a probiotic and herbal supplement for lung health. Front Nutr 2023; 10:1168582. [PMID: 37384109 PMCID: PMC10293651 DOI: 10.3389/fnut.2023.1168582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 05/24/2023] [Indexed: 06/30/2023] Open
Abstract
Introduction Dysbiosis of the gut microbiome may augment lung disease via the gut-lung axis. Proteobacteria may contribute to tissue proteolysis followed by neutrophil recruitment, lung tissue injury, and perpetuation of chronic inflammation. To study the effects of probiotics across the gut-lung axis, we sought to determine if a Lactobacillus probiotic and herbal blend was safe and well-tolerated in healthy volunteers and asthmatic patients. Methods We conducted a 1-month randomized, open-label clinical trial in Cork, Ireland with healthy and asthmatic patients who took the blend twice a day. The primary endpoint was safety with exploratory endpoints including quality of life, lung function, gut microbiome ecology, and inflammatory biomarkers. Results All subjects tolerated the blend without adverse events. Asthmatic subjects who took the blend showed significant improvements in lung function as measured by forced expiratory volume and serum short chain fatty acid levels from baseline to Week 4. The gut microbiome of asthmatic subjects differed significantly from controls, with the most prominent difference in the relative abundance of the proteobacteria Escherichia coli. Administration of the probiotic maintained overall microbial community architecture with the only significant difference being an increase in absolute abundance of the probiotic strains measured by strain-specific PCR. Conclusion This study supports the safety and efficacy potential of a Lactobacillus probiotic plus herbal blend to act on the gut-lung axis. However, due to the lack of a control group, a longer blinded, placebo-controlled study will be warranted to confirm the efficacy improvements observed in this trial. Clinical trial registration https://clinicaltrials.gov/, identifier NCT05173168.
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Affiliation(s)
- Nancy M. Wenger
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Luhua Qiao
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Teodora Nicola
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Zoha Nizami
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Isaac Martin
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Brian A. Halloran
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Kosuke Tanaka
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Michael Evans
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Xin Xu
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
| | | | | | | | - Namasivayam Ambalavanan
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Kent A. Willis
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Amit Gaggar
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Charitharth Vivek Lal
- Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
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Heinrich VA, Uvalle C, Manni ML, Li K, Mullett SJ, Donepudi SR, Clader J, Fitch A, Ellgass M, Cechova V, Qin S, Holguin F, Freeman BA, Methé BA, Morris A, Gelhaus SL. Meta-omics profiling of the gut-lung axis illuminates metabolic networks and host-microbial interactions associated with elevated lung elastance in a murine model of obese allergic asthma. FRONTIERS IN MICROBIOMES 2023; 2:1153691. [PMID: 37293566 PMCID: PMC10249466 DOI: 10.3389/frmbi.2023.1153691] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Obesity and associated changes to the gut microbiome worsen airway inflammation and hyperresponsiveness in asthma. Obesogenic host-microbial metabolomes have altered production of metabolites that may influence lung function and inflammatory responses in asthma. To understand the interplay of the gut microbiome, metabolism, and host inflammation in obesity-associated asthma, we used a multi-omics approach to profile the gut-lung axis in the setting of allergic airway disease and diet-induced obesity. We evaluated an immunomodulator, nitro-oleic acid (NO2-OA), as a host- and microbial-targeted treatment intervention for obesity-associated allergic asthma. Allergic airway disease was induced using house dust mite and cholera toxin adjuvant in C57BL6/J mice with diet-induced obesity to model obesity-associated asthma. Lung function was measured by flexiVent following a week of NO2-OA treatment and allergen challenge. 16S rRNA gene (from DNA, taxa presence) and 16S rRNA (from RNA, taxa activity) sequencing, metabolomics, and host gene expression were paired with a Treatment-Measured-Response model as a data integration framework for identifying latent/hidden relationships with linear regression among variables identified from high-dimensional meta-omics datasets. Targeting both the host and gut microbiota, NO2-OA attenuated airway inflammation, improved lung elastance, and modified the gut microbiome. Meta-omics data integration and modeling determined that gut-associated inflammation, metabolites, and functionally active gut microbiota were linked to lung function outcomes. Using Treatment-Measured-Response modeling and meta-omics profiling of the gut-lung axis, we uncovered a previously hidden network of interactions between gut levels of amino acid metabolites involved in elastin and collagen synthesis, gut microbiota, NO2-OA, and lung elastance. Further targeted metabolomics analyses revealed that obese mice with allergic airway disease had higher levels of proline and hydroxyproline in the lungs. NO2-OA treatment reduced proline biosynthesis by downregulation of pyrroline-5-carboxylate reductase 1 (PYCR1) expression. These findings are relevant to human disease: adults with mild-moderate asthma and BMI ≥ 25 had higher plasma hydroxyproline levels. Our results suggest that changes to structural proteins in the lung airways and parenchyma may contribute to heightened lung elastance and serve as a potential therapeutic target for obese allergic asthma.
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Affiliation(s)
- Victoria A. Heinrich
- Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Medical Scientist Training Program, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Crystal Uvalle
- Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, United States
| | - Michelle L. Manni
- Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Kelvin Li
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, United States
| | - Steven J. Mullett
- Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, United States
| | - Sri Ramya Donepudi
- Integrative Systems Biology Program, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Jason Clader
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, United States
| | - Adam Fitch
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, United States
| | - Madeline Ellgass
- Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, United States
| | - Veronika Cechova
- Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Shulin Qin
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, United States
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Fernando Holguin
- Division of Pulmonary Sciences and Critical Care, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Bruce A. Freeman
- Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Barbara A. Methé
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, United States
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Alison Morris
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, United States
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Clinical and Translational Science, University of Pittsburgh, Pittsburgh, PA, United States
| | - Stacy L. Gelhaus
- Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Clinical and Translational Science, University of Pittsburgh, Pittsburgh, PA, United States
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22
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Ciprandi G, Tosca MA, Drago L. Probiotics in asthma management: fiction or truth? Expert Rev Clin Immunol 2023; 19:457-460. [PMID: 37094604 DOI: 10.1080/1744666x.2023.2189103] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Affiliation(s)
| | | | - Lorenzo Drago
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
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23
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The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment. J Allergy Clin Immunol 2023; 151:706-715. [PMID: 36343772 DOI: 10.1016/j.jaci.2022.09.041] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 09/12/2022] [Accepted: 09/20/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. METHODS Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. RESULTS In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤ .037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤ .046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10-12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUCtraining: 0.82 and AUCvalidation: 0.77). CONCLUSION The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS.
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24
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Liang D, Wu F, Zhou D, Tan B, Chen T. Commercial probiotic products in public health: current status and potential limitations. Crit Rev Food Sci Nutr 2023; 64:6455-6476. [PMID: 36688290 DOI: 10.1080/10408398.2023.2169858] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Consumption of commercial probiotics for health improvement and disease treatment has increased in popularity among the public in recent years. The local shops and pharmacies are brimming with various probiotic products such as probiotic food, dietary supplement and pharmaceuticals that herald a range of health benefits, from nutraceutical benefits to pharmaceutical effects. However, although the probiotic market is expanding rapidly, there is increasing evidence challenging it. Emerging insights from microbiome research and public health demonstrate several potential limitations of the natural properties, regulatory frameworks, and market consequences of commercial probiotics. In this review, we highlight the potential safety and performance issues of the natural properties of commercial probiotics, from the genetic level to trait characteristics and probiotic properties and further to the probiotic-host interaction. Besides, the diverse regulatory frameworks and confusing probiotic guidelines worldwide have led to product consequences such as pathogenic contamination, overstated claims, inaccurate labeling and counterfeit trademarks for probiotic products. Here, we propose a plethora of available methods and strategies related to strain selection and modification, safety and efficacy assessment, and some recommendations for regulatory agencies to address these limitations to guarantee sustainability and progress in the probiotic industry and improve long-term public health and development.
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Affiliation(s)
- Dingfa Liang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- Queen Mary School, Nanchang University, Nanchang, China
| | - Fei Wu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
| | - Dexi Zhou
- National Engineering Research Centre for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China
| | - Buzhen Tan
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
| | - Tingtao Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- National Engineering Research Centre for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China
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25
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Valverde-Molina J, García-Marcos L. Microbiome and Asthma: Microbial Dysbiosis and the Origins, Phenotypes, Persistence, and Severity of Asthma. Nutrients 2023; 15:nu15030486. [PMID: 36771193 PMCID: PMC9921812 DOI: 10.3390/nu15030486] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/10/2023] [Accepted: 01/11/2023] [Indexed: 01/19/2023] Open
Abstract
The importance of the microbiome, and of the gut-lung axis in the origin and persistence of asthma, is an ongoing field of investigation. The process of microbial colonisation in the first three years of life is fundamental for health, with the first hundred days of life being critical. Different factors are associated with early microbial dysbiosis, such as caesarean delivery, artificial lactation and antibiotic therapy, among others. Longitudinal cohort studies on gut and airway microbiome in children have found an association between microbial dysbiosis and asthma at later ages of life. A low α-diversity and relative abundance of certain commensal gut bacterial genera in the first year of life are associated with the development of asthma. Gut microbial dysbiosis, with a lower abundance of Phylum Firmicutes, could be related with increased risk of asthma. Upper airway microbial dysbiosis, especially early colonisation by Moraxella spp., is associated with recurrent viral infections and the development of asthma. Moreover, the bacteria in the respiratory system produce metabolites that may modify the inception of asthma and is progression. The role of the lung microbiome in asthma development has yet to be fully elucidated. Nevertheless, the most consistent finding in studies on lung microbiome is the increased bacterial load and the predominance of proteobacteria, especially Haemophilus spp. and Moraxella catarrhalis. In this review we shall update the knowledge on the association between microbial dysbiosis and the origins of asthma, as well as its persistence, phenotypes, and severity.
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Affiliation(s)
- José Valverde-Molina
- Department of Paediatrics, Santa Lucía General University Hospital, 30202 Cartagena, Spain
| | - Luis García-Marcos
- Paediatric Allergy and Pulmonology Units, Virgen de la Arrixaca University Children’s Hospital, University of Murcia and IMIB Biomedical Research Institute, 20120 Murcia, Spain
- Correspondence:
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26
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Sadrifar S, Abbasi-Dokht T, Forouzandeh S, Malek F, Yousefi B, Salek Farrokhi A, Karami J, Baharlou R. Immunomodulatory effects of probiotic supplementation in patients with asthma: a randomized, double-blind, placebo-controlled trial. Allergy Asthma Clin Immunol 2023; 19:1. [PMID: 36593510 PMCID: PMC9806812 DOI: 10.1186/s13223-022-00753-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 12/12/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Asthma is considered to be a chronic inflammatory disorder of the airways. Probiotics are living microorganisms that are found in the human gut and have protective effects against a wide range of diseases such as allergies. The aim of this study was to investigate the improvement of clinical asthma symptoms and changes in the expression pattern of selective microRNAs in patients with asthma and the changes in IL-4 and IFN-γ plasma levels after receiving probiotics. MATERIALS AND METHODS The present study was a randomized, double-blind, placebo-controlled trial that enrolled 40 asthmatic patients. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function tests, IL-4 and IFN-γ levels, and expression of microRNAs were assessed at baseline and after treatment. RESULTS The results showed that the expression of miR-16, miR146-a and IL-4 levels in patients with asthma after receiving probiotic supplementation was significantly reduced and miR-133b expression was increased. In addition, pulmonary function tests showed a significant improvement in Forced Expiratory Volume in 1 s and Forced Vital Capacity after receiving probiotics. CONCLUSION In our study, 8-week treatment with probiotic supplementation led to reduced Th2 cells-associated IL-4 and improved Forced Expiratory Volume and Forced Vital Capacity. It appears probiotics can be used in addition to common asthma treatments.
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Affiliation(s)
- Sina Sadrifar
- grid.486769.20000 0004 0384 8779Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran ,grid.486769.20000 0004 0384 8779Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Tannaz Abbasi-Dokht
- grid.486769.20000 0004 0384 8779Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran ,grid.486769.20000 0004 0384 8779Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Sarvenaz Forouzandeh
- grid.486769.20000 0004 0384 8779Department of Internal medicine, Kosar Hospital, Semnan University of Medical Sciences, Semnan, Iran
| | - Farhad Malek
- grid.486769.20000 0004 0384 8779Department of Internal medicine, Kosar Hospital, Semnan University of Medical Sciences, Semnan, Iran
| | - Bahman Yousefi
- grid.486769.20000 0004 0384 8779Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran ,grid.486769.20000 0004 0384 8779Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Amir Salek Farrokhi
- grid.420169.80000 0000 9562 2611Department of Immunology, Pasteur Institute, Tehran, Iran
| | - Jafar Karami
- Molecular and Medicine Research Center, Khomein University of Medical Sciences, Khomein, Iran
| | - Rasoul Baharlou
- grid.486769.20000 0004 0384 8779Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran ,grid.486769.20000 0004 0384 8779Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
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27
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Khabbazi A, Ahangari Maleki M, Soltani-Zangbar MS, Yousefi M, Malek Mahdavi A. Effects of synbiotic supplementation on regulatory T cells' response in patients with axial spondyloarthritis: a randomized double-masked placebo-controlled trial. Food Funct 2022; 13:12733-12741. [PMID: 36409223 DOI: 10.1039/d2fo01377k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
This study was conducted on samples from patients enrolled in a randomized double-masked placebo-controlled trial on the effect of synbiotic supplementation on the IL-17/IL-23 pathway and disease activity in patients with axial spondyloarthritis (axSpA) to investigate the effects of synbiotic supplementation on regulatory T (Treg) cells' response in these patients. Forty-eight axSpA patients were randomized to take one synbiotic capsule or placebo daily for 12 weeks. Treg cell proportion, gene expression of forkhead box protein P3 (Foxp3), microRNA (miRNA)-25, miRNA-106b, miRNA-146a, interleukin (IL)-10, and transforming growth factor (TGF)-β as well as serum IL-10 and TGF-β levels were assessed before and after the trial. Thirty-eight patients (19 in each group) completed the trial. The proportion of Treg cells (P < 0.001), the gene expression of FoxP3 (P < 0.001), IL-10 (P = 0.001), TGF-β (P < 0.001), and miRNA-146a (P < 0.001) and serum IL-10 (P = 0.003) and TGF-β (P = 0.002) levels significantly increased compared to the baseline in the synbiotic group. Additionally, a significant reduction in the gene expression of miRNA-25 (P < 0.001) and miRNA-106b (P < 0.001) was observed in the synbiotic group. Significant between-group differences were observed in the proportion of Treg cells (P = 0.024) and the gene expression of FoxP3 (P = 0.010), IL-10 (P = 0.002), TGF-β (P = 0.016), miRNA-25 (P = 0.008), miRNA-106b (P = 0.001), and miRNA-146a (P = 0.010). Differences in the serum levels of IL-10 and TGF-β between the groups were not significant. As a conclusion, synbiotic supplementation could modulate Treg cells' response in axSpA patients and thus can be promising as an adjunctive therapy. Additional investigations would help in further clarifying the subject.
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Affiliation(s)
- Alireza Khabbazi
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Masoud Ahangari Maleki
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | | | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aida Malek Mahdavi
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Rahat Breathe and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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28
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Wang X, Tan X, Zhou J. Effectiveness and safety of probiotic therapy for pediatric allergic rhinitis management: A systematic review and meta-analysis. Int J Pediatr Otorhinolaryngol 2022; 162:111300. [PMID: 36084479 DOI: 10.1016/j.ijporl.2022.111300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 08/15/2022] [Accepted: 08/27/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVE This meta-analysis aimed to evaluate the effectiveness and safety of probiotics for allergic rhinitis (AR) management in children. METHODS In total, 6 databases were searched, and 26 randomized controlled trials that compared the effects of probiotics with those not using probiotics in pediatric AR were included. Methodological quality was assessed using the Cochrane risk-of-bias tool. Data for relevant endpoints were extracted and analyzed. RESULTS Our meta-analysis of the effectiveness of probiotics for pediatric AR showed that probiotics improved the remission rate of nasal symptoms (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.04 to 1.40; P = 0.01), reduced the Total Nasal Symptoms Scores (TNSS) (weighted mean difference (WMD) -2.58, 95% CI -2.77 to -2.39; P < 0.00001) and the total scores of Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) (for frequency of symptoms: WMD -9.51, 95% CI -10.34 to -8.69; P < 0.00001; and for level of bother: WMD -9.27, 95% CI -10.13 to -8.41; P < 0.00001). Furthermore, they reduced the serum levels of interleukin-4 (IL-4) (WMD -13.86 ng/L, 95% CI -15.92 to -11.81; P < 0.00001), IL-6 (WMD -13.70 pg/mL, 95% CI -16.34 to -11.07; P < 0.00001), and IL-17(WMD -5.41 pg/mL, 95% CI -7.29 to -3.52; P < 0.00001), and significantly elevated the serum levels of interferon-γ (WMD 9.08 ng/L, 95% CI 8.10 to 10.06; P < 0.00001) and IL-10 (WMD 7.82 pg/mL, 95% CI 5.01 to 10.63; P < 0.00001). Probiotics also reduced the duration of cetirizine use in pediatric AR (WMD -2.88 days, 95% CI -4.50 to -1.26; P < 0.0005). No obvious adverse reactions were found to be related to probiotic treatment. CONCLUSIONS This meta-analysis indicated that probiotic therapy can partially improve pediatric AR outcomes, assisted by modulating immune balance and reducing anti-allergic medication use, without obvious adverse reactions.
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Affiliation(s)
- Xia Wang
- Department of Pediatrics, The Second Affiliated Hospital of Army Medical University, Army Medical University Xinqiao Hospital, Chongqing, 400037, China.
| | - Xiangsheng Tan
- The First Hospital Affiliated to Army Medical University, Chongqing, 400038, China.
| | - Jiwei Zhou
- Department of the General Practice, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.
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29
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Iftikhar H, Awan MO, Awan MS, Mustafa K, Das JK, Ahmed SK. Role of Probiotics in Patients with Allergic Rhinitis: A Systematic Review of Systematic Reviews. Int Arch Otorhinolaryngol 2022; 26:e744-e752. [PMID: 36405454 PMCID: PMC9668414 DOI: 10.1055/s-0042-1749370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 04/17/2022] [Indexed: 10/18/2022] Open
Abstract
Introduction Allergic rhinitis (AR) is estimated to affect up to 30% of the world population. With the rise in cases, newer treatment modalities have been explored. Probiotics have shown to reduce symptoms of AR and improve quality of life. A few systematic reviews have been published aiming to assess the role of probiotics in AR. Objectives To consolidate the recent evidence with an overview of systematic reviews by extracting data regarding subjective outcomes (from quality of life questionnaires, the Total Nasal Symptom Score, the Total Ocular Symptom Score, the Daily Total Symptom Score, the incidence of AR, and the Rhinitis Total Symptom Score) and objective outcomes (levels of antigen-specific immunoglobulin E [IgE], total IgE, interleukin 10 [IL-10], interferon gamma [IFNG], eosinophil, and the T helper 1/T helper 2 [Th1/Th2] ratio). Data Synthesis We conducted a literature search on the PubMed, EBSCO CINAHL, EBSCO Dentistry & Oral Sciences Source, and Cochrane Library up to April 14, 2020. The qualitative assessment was performed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR-2) tool. A total of 419 titles were screened, and 3 systematic reviews met our eligibility criteria. Probiotics in the treatment of AR have been shown to improve quality of life, the total nasal and ocular symptom scores, the daily total symptom scores and Th1/Th2 ratio. No difference was ascertained for rhinitis total symptom score, and the rates of antigen-specific IgE, total IgE, IL-10, INFG and eosinophil. Conclusion The present review showed that there is considerable evidence that probiotics are useful in the treatment of AR. Further randomized trials targeting the limitations of the currently-available evidence can help ascertain the usefulness of probiotics in cases of AR.
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Affiliation(s)
- Haissan Iftikhar
- Department of Otolaryngology, Rawal Institute of Health Sciences, Islamabad, Pakistan
| | - Muhammad Ozair Awan
- Department of Surgery, Aga Khan University Medical College, Karachi, Pakistan
| | | | - Khawaja Mustafa
- Department of Surgery, Aga Khan University Medical College, Karachi, Pakistan
| | - Jai K. Das
- Division of Women and Child Health, Aga Khan University, Karachi, Pakistan
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30
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Chen PC, Hsieh MH, Kuo WS, Wu LSH, Kao HF, Liu LF, Liu ZG, Jeng WY, Wang JY. Moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein of Lactobacillus gasseri attenuates allergic asthma via immunometabolic change in macrophages. J Biomed Sci 2022; 29:75. [PMID: 36175886 PMCID: PMC9520948 DOI: 10.1186/s12929-022-00861-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/23/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The extra-intestinal effects of probiotics for preventing allergic diseases are well known. However, the probiotic components that interact with host target molecules and have a beneficial effect on allergic asthma remain unknown. Lactobacillus gasseri attenuates allergic airway inflammation through the activation of peroxisome proliferator- activated receptor γ (PPARγ) in dendritic cells. Therefore, we aimed to isolate and investigate the immunomodulatory effect of the PPARγ activation component from L. gasseri. METHODS Culture supernatants of L. gasseri were fractionated and screened for the active component for allergic asthma. The isolated component was subjected to in vitro functional assays and then cloned. The crystal structure of this component protein was determined using X-ray crystallography. Intrarectal inoculation of the active component-overexpressing Clear coli (lipopolysaccharide-free Escherichia coli) and intraperitoneal injection of recombinant component protein were used in a house dust mite (HDM)-induced allergic asthma mouse model to investigate the protective effect. Recombinant mutant component proteins were assayed, and their structures were superimposed to identify the detailed mechanism of alleviating allergic inflammation. RESULTS A moonlighting protein, glycolytic glyceraldehyde 3-phosphate dehydrogenase (GAPDH), LGp40, that has multifunctional effects was purified from cultured L. gasseri, and the crystal structure was determined. Both intrarectal inoculation of LGp40-overexpressing Clear coli and intraperitoneal administration of recombinant LGp40 protein attenuated allergic inflammation in a mouse model of allergic asthma. However, CDp40, GAPDH isolated from Clostridium difficile did not possess this anti-asthma effect. LGp40 redirected allergic M2 macrophages toward the M1 phenotype and impeded M2-prompted Th2 cell activation through glycolytic activity that induced immunometabolic changes. Recombinant mutant LGp40, without enzyme activity, showed no protective effect against HDM-induced airway inflammation. CONCLUSIONS We found a novel mechanism of moonlighting LGp40 in the reversal of M2-prompted Th2 cell activation through glycolytic activity, which has an important immunoregulatory role in preventing allergic asthma. Our results provide a new strategy for probiotics application in alleviating allergic asthma.
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Affiliation(s)
- Pei-Chi Chen
- Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, No. 2, Yuh-Der Road, Taichung City, 404, Taiwan.,Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan
| | - Miao-Hsi Hsieh
- Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, No. 2, Yuh-Der Road, Taichung City, 404, Taiwan
| | - Wen-Shuo Kuo
- Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, No. 2, Yuh-Der Road, Taichung City, 404, Taiwan.,School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing, China
| | - Lawrence Shih-Hsin Wu
- Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, No. 2, Yuh-Der Road, Taichung City, 404, Taiwan.,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Hui-Fang Kao
- Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan
| | - Li-Fan Liu
- Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Zhi-Gang Liu
- Department of Respirology and Allergy, Third Affiliated Hospital of Shengzhen University, Shengzhen, China
| | - Wen-Yih Jeng
- University Center for Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. .,Department of Biochemistry and Molecular Biology, National Cheng Kung University, No. 1, University Road, Tainan City, 701, Taiwan.
| | - Jiu-Yao Wang
- Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, No. 2, Yuh-Der Road, Taichung City, 404, Taiwan. .,Children's Hospital, China Medical University, Taichung, Taiwan.
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Fiocchi A, Cabana MD, Mennini M. Current Use of Probiotics and Prebiotics in Allergy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:2219-2242. [PMID: 35792336 DOI: 10.1016/j.jaip.2022.06.038] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 06/27/2022] [Accepted: 06/27/2022] [Indexed: 01/06/2023]
Abstract
The microbiome plays an important role in the pathogenesis of allergic diseases. This review updates the reader on studies aimed at influencing allergic diseases through modulation of the gut microflora. A nonsystematic review of the literature was performed, focusing on relevant trials evaluating the effect of probiotics/prebiotics/symbiotics in the prevention and treatment of allergic disease. For each allergic disease, we were able to find not only a substantial number of clinical trials but also systematic reviews. Specific guidelines, based on systematic reviews and meta-analyses, are available for the prevention of allergic disease and for the treatment of food allergy. In each of the areas examined-allergic rhinitis, allergic asthma, atopic dermatitis, food allergy, and gastrointestinal allergies-there are substantial uncertainties in the efficacy of gut microflora modulation in prevention and treatment. At present, practicing clinicians can avail themselves of intestinal flora modulators as an adjunct in the prevention of atopic dermatitis but not of other forms of allergic diseases. Their effects on the treatment of allergic diseases remain controversial.
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Affiliation(s)
- Alessandro Fiocchi
- Translational Research in Pediatric Specialities Area, Allergy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
| | - Michael D Cabana
- Department of Pediatrics, Albert Einstein College of Medicine and the Children's Hospital at Montefiore, Bronx, NY
| | - Maurizio Mennini
- Translational Research in Pediatric Specialities Area, Allergy Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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Uwaezuoke SN, Ayuk AC, Eze JN, Odimegwu CL, Ndiokwelu CO, Eze IC. Postnatal probiotic supplementation can prevent and optimize treatment of childhood asthma and atopic disorders: A systematic review of randomized controlled trials. Front Pediatr 2022; 10:956141. [PMID: 36061384 PMCID: PMC9437454 DOI: 10.3389/fped.2022.956141] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 08/04/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Although several randomized controlled trials (RCTs) published over the past 5 years show that prenatal or postnatal probiotics may prevent or optimize the treatment of childhood asthma and atopic disorders, findings from the systematic reviews and meta-analyses of these studies appear inconsistent. More recent RCTs have focused on postnatal probiotics, and linked specific probiotic strains to better disease outcomes. OBJECTIVE This systematic review aimed to determine if postnatal probiotics are as effective as prenatal probiotics in preventing or treating childhood asthma and atopic disorders. METHODS We searched the PubMed, Medline, Google Scholar, and EMBASE databases for RCTs published within the past 5 years (from 2017 to 2022). We included only full-text RCTs on human subjects published in or translated into the English language. We retrieved relevant data items with a preconceived data-extraction form and assessed the methodological quality of the selected RCTs using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials. We qualitatively synthesized the retrieved data to determine any significant differences in study endpoints of the probiotic and placebo groups. RESULTS A total of 1,320 participants (688 and 632 in the probiotic and placebo groups) from six RCTs were investigated. One RCT showed that early Lactobacillus rhamnosus GG (LGG) led to a reduction in the cumulative incidence rate of asthma. Another study demonstrated that mixed strains of Lactobacillus paracasei and Lactobacillus fermentum could support clinical improvement in children with asthma while one trial reported a significant reduction in the frequency of asthma exacerbations using a mixture of Ligilactobacillus salivarius and Bifidobacterium breve. Three trials showed that a combination of LGG and Bifidobacterium animalis subsp lactis, Lactobacillus rhamnosus alone, and a probiotic mixture of Lactobacillus ŁOCK strains improved clinical outcomes in children with atopic dermatitis and cow-milk protein allergy. CONCLUSIONS Postnatal strain-specific probiotics (in single or mixed forms) are beneficial in preventing and treating atopic dermatitis and other allergies. Similarly, specific strains are more effective in preventing asthma or improving asthma outcomes. We recommend more interventional studies to establish the most useful probiotic strain in these allergic diseases.
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Affiliation(s)
- Samuel N. Uwaezuoke
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
- Department of Pediatrics, College of Medicine, University of Nigeria, Ituku-Ozalla Enugu Campus, Enugu, Nigeria
| | - Adaeze C. Ayuk
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
- Department of Pediatrics, College of Medicine, University of Nigeria, Ituku-Ozalla Enugu Campus, Enugu, Nigeria
| | - Joy N. Eze
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
- Department of Pediatrics, College of Medicine, University of Nigeria, Ituku-Ozalla Enugu Campus, Enugu, Nigeria
| | - Chioma L. Odimegwu
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
- Department of Pediatrics, College of Medicine, University of Nigeria, Ituku-Ozalla Enugu Campus, Enugu, Nigeria
| | - Chibuzo O. Ndiokwelu
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
| | - Ikenna C. Eze
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
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Voo PY, Wu CT, Sun HL, Ko JL, Lue KH. Effect of combination treatment with Lactobacillus rhamnosus and corticosteroid in reducing airway inflammation in a mouse asthma model. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2022; 55:766-776. [PMID: 35487817 DOI: 10.1016/j.jmii.2022.03.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 02/13/2022] [Accepted: 03/24/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Asthma is a complex multifactorial chronic airway inflammatory disease with diverse phenotypes and levels of severity and is associated with significant health and economic burden. In a certain population of asthma patients, the symptoms cannot be well controlled with steroid. There has been long standing interest in the use of probiotics for treating allergic diseases. The purpose of this study is to investigate whether the combination of Lactobacillus rhamnosus GG (LGG) with prednisolone could reduce the dosage of glucocorticoid in controlling airway inflammation in a murine model for allergic asthma. MATERIAL AND METHODS We used Der p 2-sensitized asthma model in female BALB/c mice. The animals were treated with 75 μl or 50 μl oral prednisolone or combination treatment of these two doses of oral prednisolone with LGG. Airway hyperresponsiveness, serum specific IgE/IgG1/IgG2a, infiltrating inflammatory cells in lung and cytokines were assessed. RESULTS Compared to 75 μl prednisolone, a lower dose of prednisolone with 50 μl was less satisfactory in suppressing airway hyperresponsives, serum IgE and IgG1, Th2 cytokines and inflammatory cytokines such as IL-6, IL-8 and IL-17 as well as infiltrating inflammatory cells. However, combination of 50 μl prednisolone and LGG decreased airway resistance and serum IgE and IgG1, inhibited the production of IL-4, IL-5, IL-6, IL-8, IL-13 and IL-17, upregulated serum IgG2a and enhanced Th1 immune response. CONCLUSIONS LGG may reduce the dosage of prednisolone and thus may be beneficial in the treatment of asthma.
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Affiliation(s)
- Pit-Yee Voo
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
| | - Chia-Ta Wu
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan.
| | - Hai-Lun Sun
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jiunn-Liang Ko
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Ko-Haung Lue
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
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Chen N, Liu F, Gao Q, Wang R, Zhang L, Li Y. A Meta-Analysis of Probiotics for the Treatment of Allergic Airway Diseases in Children and Adolescents. Am J Rhinol Allergy 2022; 36:480-490. [PMID: 35238209 DOI: 10.1177/19458924221080159] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Allergic airway disease is a chronic airway allergic inflammatory disease including allergic rhinitis (AR) and allergic asthma which is common in children and adolescents. Recently the probiotics has been becoming a supplementary or alternative therapy to allergic diseases, however the effect of them has not been clearly established. OBJECTIVE The purpose of the present meta-analysis was to evaluate the effectiveness of probiotics on allergic airway disease including AR and allergic asthma in children and adolescents. METHODS We performed a comprehensive search on PubMed, Cochrane Library, EMBASE for relevant publications from 1 Jan 2000 to 1 July 2021. Physical examinations, Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs), Total Nasal Symptom Score (TNSS), Nasal or Eye Symptom Score (NSS or ESS), serum allergen-specific IgE, and eosinophil were used as evaluating indicators for AR and allergic asthma in children and adolescents. The meta-analysis was performed using Review Manager (RevMan, Version 5.3). RESULTS 15 randomized controlled trials (RCTs) with a total of 1388 participants were included for the meta-analysis. Among them, 729 patients treated with probiotics served as the probiotics group, and 659 patients with placebo as control group. Significantly greater reduction in PRQLQs from baseline to endpoint (SMD = -2.57, 95% CI [ - 4.66, -0.48] P < 0.01), NSS (SMD = -1.43, 95% CI [ - 1.63, - 1.23], P < 0.01) and ESS (total MD = -1.67, 95% CI [ - 1.79, - 1.55], P < 0.01) were observed in probiotics group compared to control group. Probiotics have no significant effect to serum IgE and eosinophils (P > 0.01). CONCLUSION The results of this meta-analysis indicated that probiotics treatment may reduce PRQLQs, NSS, ESS in patients with allergic airway disease. More research involving the mechanism of probiotics are needed to clarify the role of probiotics in AR and allergic asthma in children and adolescents.
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Affiliation(s)
- Na Chen
- Department of Otolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Fang Liu
- Department of Otolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Qiang Gao
- Department of Gastroenterology and Hepatology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Rui Wang
- Department of Otolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Lei Zhang
- Department of Otolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Youwei Li
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
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Probiotics in Children with Asthma. CHILDREN 2022; 9:children9070978. [PMID: 35883962 PMCID: PMC9316460 DOI: 10.3390/children9070978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 12/11/2022]
Abstract
A type-2 immune response usually sustains wheezing and asthma in children. In addition, dysbiosis of digestive and respiratory tracts is detectable in patients with wheezing and asthma. Probiotics may rebalance immune response, repair dysbiosis, and mitigate airway inflammation. As a result, probiotics may prevent asthma and wheezing relapse. There is evidence that some probiotic strains may improve asthma outcomes in children. In this context, the PROPAM study provided evidence that two specific strains significantly prevented asthma exacerbations and wheezing episodes. Therefore, oral probiotics could be used as add-on asthma therapy in managing children with asthma, but the choice should be based on documented evidence.
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36
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Farzan S, Coyle T, Coscia G, Rebaza A, Santiago M. Clinical Characteristics and Management Strategies for Adult Obese Asthma Patients. J Asthma Allergy 2022; 15:673-689. [PMID: 35611328 PMCID: PMC9124473 DOI: 10.2147/jaa.s285738] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 05/05/2022] [Indexed: 11/23/2022] Open
Abstract
The rates of asthma and obesity are increasing concurrently in the United States. Epidemiologic studies demonstrate that the incidence of asthma increases with obesity. Furthermore, obese individuals have asthma that is more severe, harder to control, and resistant to standard medications. In fact, specific asthma-obesity phenotypes have been identified. Various pathophysiologic mechanisms, including mechanical, inflammatory, metabolic and microbiome-associated, are at play in promulgating the obese-asthma phenotypes. While standard asthma medications, such as inhaled corticosteroids and biologics, are currently used to treat obese asthmatics, they may have limited effectiveness. Targeting the underlying aberrant processes, such as addressing steroid resistance, microbiome, metabolic and weight loss approaches, may be helpful.
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Affiliation(s)
- Sherry Farzan
- Division of Allergy & Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Great Neck, NY, USA
- Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Queens, NY, USA
- Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Manhasett, NY, USA
- Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY, USA
- Correspondence: Sherry Farzan, Division of Allergy & Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, 865 Northern Blvd, Suite 101, Great Neck, NY, 11021, USA, Tel +1 516-622-5070, Fax +1 516-622-5060, Email
| | - Tyrone Coyle
- Division of Allergy & Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Great Neck, NY, USA
- Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Queens, NY, USA
- Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Manhasett, NY, USA
| | - Gina Coscia
- Division of Allergy & Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Great Neck, NY, USA
- Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Queens, NY, USA
- Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Manhasett, NY, USA
| | - Andre Rebaza
- Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Queens, NY, USA
- Division of Pediatric Pulmonology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, New York, NY, USA
| | - Maria Santiago
- Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Queens, NY, USA
- Division of Pediatric Pulmonology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, New York, NY, USA
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Li L, Fang Z, Lee YK, Zhao J, Zhang H, Peng H, Zhang Y, Lu W, Chen W. Efficacy and Safety of Lactobacillus reuteri CCFM1040 in Allergic Rhinitis and Asthma: A Randomized, Placebo-Controlled Trial. Front Nutr 2022; 9:862934. [PMID: 35464005 PMCID: PMC9022948 DOI: 10.3389/fnut.2022.862934] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 02/14/2022] [Indexed: 11/27/2022] Open
Abstract
The coexistence of allergic rhinitis (AR) and asthma reinforces the concept of “one airway, one disease,” which has prompted the exploration for a single intervention to treat both diseases. Lactobacillus reuteri CCFM1040 (CCFM1040) was found to be an inhibitor of the common pathogenesis of AR and asthma in our previous studies. This study presented a randomized, placebo-controlled trial to investigate the clinical effects of CCFM1040 on both diseases. The total symptom score (TSS), the quality of life (QoL), and the modulation in the gut microbiota of patients with AR, the Asthma Control and Test (ACT) of patients with asthma, and the safety of both AR and asthma were measured. In patients with AR, CCFM1040 numerically decreased TSS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), 3 nasal scores in TSS (nasal congestion, watery eyes, and rhinorrhea), and sleep and significantly improved (P = 0.014) non-nose/eye symptoms. The ACT score was numerically increased in patients with asthma (from partially controlled to well-controlled). Significant microbial (from class level to genus level) and metabolic differences (P < 0.05) were found in patients with AR. No adverse reactions were observed. No effect on the blood and urine routine indexes. CCFM1040 has a potential benefit on both diseases. Further studies based on these findings will help to optimize the management of AR and asthma.
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Huang J, Zhang J, Wang X, Jin Z, Zhang P, Su H, Sun X. Effect of Probiotics on Respiratory Tract Allergic Disease and Gut Microbiota. Front Nutr 2022; 9:821900. [PMID: 35295917 PMCID: PMC8920559 DOI: 10.3389/fnut.2022.821900] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 01/31/2022] [Indexed: 12/12/2022] Open
Abstract
Allergy is a hypersensitivity reaction triggered by specific cell or antibody-mediated immune mechanisms. Allergies have increased in industrialized countries in recent decades. The rise in allergic respiratory diseases such as allergic rhinitis (AR) and allergic asthma (AA) is a potential threat to public health. Searches were conducted using PubMed, Google Scholar and Medline using the following key terms: allergic rhinitis OR asthma AND probiotics, allergic airway inflammation AND immune disorders, probiotics OR gut microbiota AND allergic disease, probiotics AND inflammatory. Studies from all years were included, specifically those published within the last 10 years. Some review articles and their reference lists were searched to identify related articles. The role of microbiota in respiratory allergic diseases has attracted more and more attention. Pieces of evidence suggested that the development of allergic diseases causes a possible imbalance in the composition of the gut microbiota. Compared to colonized mice, germ-free mice exhibit exaggerated allergic airway responses, suggesting that microbial host interactions play an important role in the development of allergic diseases. Probiotics modulate both the innate and adaptive inflammatory immune responses, often used as dietary supplements to provide health benefits in gastrointestinal disorders. Probiotics may serve as immunomodulators and activators of host defense pathways. Besides, oral probiotics can modulate the immune response in the respiratory system. Recently, studies in humans and animals have demonstrated the role of probiotic in RA and AA. To understand the characterization, microbiota, and the potential role of probiotics intervention of AA/AR, this review provides an overview of clinical features of AA and AR, probiotics for the prevention and treatment of AR, AA, changes in gut microbiota, and their mechanisms of action.
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Affiliation(s)
- Jinli Huang
- Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Juan Zhang
- Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Xingzhi Wang
- Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Zenghui Jin
- Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Panpan Zhang
- Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Hui Su
- Department of Geratology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Xin Sun
- Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
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Brennan M, McDonnell MJ, Harrison MJ, Duignan N, O'Regan A, Murphy DM, Ward C, Rutherford RM. Antimicrobial therapies for prevention of recurrent acute exacerbations of COPD (AECOPD): beyond the guidelines. Respir Res 2022; 23:58. [PMID: 35287677 PMCID: PMC8919139 DOI: 10.1186/s12931-022-01947-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 02/04/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. MAIN TEXT There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. CONCLUSION Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
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Affiliation(s)
- Michelle Brennan
- Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland.
| | - M J McDonnell
- Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland
| | - M J Harrison
- Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland
| | - N Duignan
- Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland
| | - A O'Regan
- Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland
| | - D M Murphy
- Department of Respiratory Medicine, Cork University Hospital, Galway, Ireland
| | - C Ward
- Department of Translational and Clinical Research Institute, Faculty of Clinical Sciences, University of Newcastle Upon Tyne, Newcastle Upon Tyne, UK
| | - R M Rutherford
- Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland
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The Probiotics in Pediatric Asthma Management (PROPAM) Study in the Primary Care Setting: A Randomized, Controlled, Double-Blind Trial with Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706). J Immunol Res 2022; 2022:3837418. [PMID: 35083341 PMCID: PMC8786459 DOI: 10.1155/2022/3837418] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 12/13/2021] [Accepted: 01/04/2022] [Indexed: 12/21/2022] Open
Abstract
Background Type-2 inflammation commonly marks asthma in childhood. Also, gut and lung dysbiosis is detectable in patients with asthma. Strain-related probiotic supplementation may restore a physiological immune response, dampen airway inflammation, and repair dysbiosis. Therefore, the probiotics in pediatric asthma management (PROPAM) study is aimed at demonstrating that Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) mixture could reduce asthma exacerbations in children, followed in a primary care setting. Methods The study was randomized, placebo-controlled, and double-blind. It involved 11 Italian primary care pediatricians. The probiotic mixture (containing Ligilactobacillus salivarius LS01 1 × 109 live cells and Bifidobacterium breve B632 1 × 109 live cells) or placebo was taken twice daily (1 sachet in the morning and 1 in the evening) for eight weeks and subsequently once daily for a further eight weeks. Outcomes included number, severity, and duration of asthma exacerbations, intensity of maintenance and as need treatments, and safety. Results The per-protocol population included 422 children (mean age seven years, 240 males and 182 females). The probiotic mixture significantly reduced the number of asthmatic exacerbations (OR = 3.17). In addition, the number of children with two exacerbations was less than a third in the active group (OR = 3.65). Conclusions This PROPAM study demonstrated that probiotic strains Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) were safe and significantly reduced by more than a third the frequency of asthma exacerbations. At present, the first-line treatment of asthma is still drug-based, but specific strains of probiotics may be auxiliary remedies.
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Tramper‐Stranders G, Ambrożej D, Arcolaci A, Atanaskovic‐Markovic M, Boccabella C, Bonini M, Karavelia A, Mingomataj E, O' Mahony L, Sokolowska M, Untersmayr E, Feleszko W. Dangerous liaisons: Bacteria, antimicrobial therapies, and allergic diseases. Allergy 2021; 76:3276-3291. [PMID: 34390006 DOI: 10.1111/all.15046] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 07/31/2021] [Indexed: 12/15/2022]
Abstract
Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.
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Affiliation(s)
- Gerdien Tramper‐Stranders
- Department of Pediatrics Franciscus Gasthuis & Vlietland Rotterdam the Netherlands
- Department of Neonatology Erasmus Medical CenterSophia Children's Hospital Rotterdam the Netherlands
| | - Dominika Ambrożej
- Department of Pediatric Pneumonology and Allergy Medical University of Warsaw Warsaw Poland
- Doctoral School Medical University of Warsaw Warsaw Poland
| | - Alessandra Arcolaci
- Immunology Unit University of Verona and General Hospital Borgo Roma Hospital Verona Italy
| | | | - Cristina Boccabella
- Department of Cardiovascular and Thoracic Sciences Università Cattolica del Sacro CuoreFondazione Policlinico Universitario A. Gemelli – IRCCS Rome Italy
| | - Matteo Bonini
- Department of Cardiovascular and Thoracic Sciences Università Cattolica del Sacro CuoreFondazione Policlinico Universitario A. Gemelli – IRCCS Rome Italy
- National Heart and Lung Institute (NHLI) Imperial College London London UK
| | - Aspasia Karavelia
- Department of Ear‐Nose‐Throat surgery General Hospital of Kozani Kozani Greece
| | - Ervin Mingomataj
- Department of Allergology & Clinical Immunology ‘Mother Theresa’ School of Medicine Tirana Albania
| | - Liam O' Mahony
- Departments of Medicine and Microbiology APC Microbiome IrelandNational University of Ireland Cork Ireland
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Zurich Switzerland
| | - Eva Untersmayr
- Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Wojciech Feleszko
- Department of Pediatric Pneumonology and Allergy Medical University of Warsaw Warsaw Poland
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Jeong J, Lee HK. The Role of CD4 + T Cells and Microbiota in the Pathogenesis of Asthma. Int J Mol Sci 2021; 22:11822. [PMID: 34769255 PMCID: PMC8584410 DOI: 10.3390/ijms222111822] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/26/2021] [Accepted: 10/29/2021] [Indexed: 12/22/2022] Open
Abstract
Asthma, a chronic respiratory disease involving variable airflow limitations, exhibits two phenotypes: eosinophilic and neutrophilic. The asthma phenotype must be considered because the prognosis and drug responsiveness of eosinophilic and neutrophilic asthma differ. CD4+ T cells are the main determinant of asthma phenotype. Th2, Th9 and Tfh cells mediate the development of eosinophilic asthma, whereas Th1 and Th17 cells mediate the development of neutrophilic asthma. Elucidating the biological roles of CD4+ T cells is thus essential for developing effective asthma treatments and predicting a patient's prognosis. Commensal bacteria also play a key role in the pathogenesis of asthma. Beneficial bacteria within the host act to suppress asthma, whereas harmful bacteria exacerbate asthma. Recent literature indicates that imbalances between beneficial and harmful bacteria affect the differentiation of CD4+ T cells, leading to the development of asthma. Correcting bacterial imbalances using probiotics reportedly improves asthma symptoms. In this review, we investigate the effects of crosstalk between the microbiota and CD4+ T cells on the development of asthma.
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Affiliation(s)
| | - Heung Kyu Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea;
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Adjunctive Probiotics Alleviates Asthmatic Symptoms via Modulating the Gut Microbiome and Serum Metabolome. Microbiol Spectr 2021; 9:e0085921. [PMID: 34612663 PMCID: PMC8510161 DOI: 10.1128/spectrum.00859-21] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Asthma is a multifactorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics have shown anti-inflammatory effects and could regulate the gut-lung axis. Thus, a 3-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma. Fifty-five asthmatic patients were randomly assigned to a probiotic group (n = 29; received Bifidobacterium lactis Probio-M8 powder and Symbicort Turbuhaler) and a placebo group (n = 26; received placebo and Symbicort Turbuhaler), and all 55 subjects provided details of their clinical history and demographic data. However, only 31 patients donated a complete set of fecal and blood samples at all three time points for further analysis. Compared with those of the placebo group, co-administering Probio-M8 with Symbicort Turbuhaler significantly decreased the fractional exhaled nitric oxide level at day 30 (P = 0.049) and improved the asthma control test score at the end of the intervention (P = 0.023). More importantly, the level of alveolar nitric oxide concentration decreased significantly among the probiotic receivers at day 30 (P = 0.038), and the symptom relief effect was even more obvious at day 90 (P = 0.001). Probiotic co-administration increased the resilience of the gut microbiome, which was reflected by only minor fluctuations in the gut microbiome diversity (P > 0.05, probiotic receivers; P < 0.05, placebo receivers). Additionally, the probiotic receivers showed significantly changes in some species-level genome bins (SGBs), namely, increases in potentially beneficial species Bifidobacterium animalis, Bifidobacterium longum, and Prevotella sp. CAG and decreases in Parabacteroides distasonis and Clostridiales bacterium (P < 0.05). Compared with that of the placebo group, the gut metabolic potential of probiotic receivers exhibited increased levels of predicted microbial bioactive metabolites (linoleoyl ethanolamide, adrenergic acid, erythronic acid) and serum metabolites (5-dodecenoic acid, tryptophan, sphingomyelin) during/after intervention. Collectively, our results suggested that co-administering Probio-M8 synergized with conventional therapy to alleviate diseases associated with the gut-lung axis, like asthma, possibly via activating multiple anti-inflammatory pathways. IMPORTANCE The human gut microbiota has a potential effect on the pathogenesis of asthma and is closely related to the disease phenotype. Our trial has demonstrated that co-administering Probio-M8 synergized with conventional therapy to alleviate asthma symptoms. The findings of the present study provide new insights into the pathogenesis and treatment of asthma, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
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Depoorter L, Vandenplas Y. Probiotics in Pediatrics. A Review and Practical Guide. Nutrients 2021; 13:2176. [PMID: 34202742 PMCID: PMC8308463 DOI: 10.3390/nu13072176] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/17/2021] [Accepted: 06/21/2021] [Indexed: 02/07/2023] Open
Abstract
The potential benefit of the administration of probiotics in children has been studied in many settings globally. Probiotics products contain viable micro-organisms that confer a health benefit on the host. Beneficial effects of selected probiotic strains for the management or prevention of selected pediatric conditions have been demonstrated. The purpose of this paper is to provide an overview of current available evidence on the efficacy of specific probiotics in selected conditions to guide pediatricians in decision-making on the therapeutic or prophylactic use of probiotic strains in children. Evidence to support the use of certain probiotics in selected pediatric conditions is often available. In addition, the administration of probiotics is associated with a low risk of adverse events and is generally well tolerated. The best documented efficacy of certain probiotics is for treatment of infectious gastroenteritis, and prevention of antibiotic-associated, Clostridioides difficile-associated and nosocomial diarrhea. Unfortunately, due to study heterogeneity and in some cases high risk of bias in published studies, a broad consensus is lacking for specific probiotic strains, doses and treatment regimens for some pediatric indications. The current available evidence thus limits the systematic administration of probiotics. The most recent meta-analyses and reviews highlight the need for more well-designed, properly powered, strain-specific and dedicated-dose response studies.
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Affiliation(s)
| | - Yvan Vandenplas
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, 1090 Brussels, Belgium;
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Johnson D, Thurairajasingam S, Letchumanan V, Chan KG, Lee LH. Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder. Nutrients 2021; 13:nu13051728. [PMID: 34065187 PMCID: PMC8161395 DOI: 10.3390/nu13051728] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/21/2022] Open
Abstract
The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota–gut–brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.
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Affiliation(s)
- Dinyadarshini Johnson
- Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia;
| | - Sivakumar Thurairajasingam
- Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor Bahru 80100, Malaysia;
| | - Vengadesh Letchumanan
- Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia;
- Correspondence: (V.L.); (K.-G.C.); or (L.-H.L.); Tel.: +60-355-146-261 (V.L.); +60-379-677-748 (K.-G.C.); +60-355-145-887 (L.-H.L.)
| | - Kok-Gan Chan
- Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia
- International Genome Centre, Jiangsu University, Zhenjiang 212013, China
- Correspondence: (V.L.); (K.-G.C.); or (L.-H.L.); Tel.: +60-355-146-261 (V.L.); +60-379-677-748 (K.-G.C.); +60-355-145-887 (L.-H.L.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia;
- Correspondence: (V.L.); (K.-G.C.); or (L.-H.L.); Tel.: +60-355-146-261 (V.L.); +60-379-677-748 (K.-G.C.); +60-355-145-887 (L.-H.L.)
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46
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Bi XD, Lu BZ, Pan XX, Liu S, Wang JY. Adjunct therapy with probiotics for chronic urticaria in children: randomised placebo-controlled trial. Allergy Asthma Clin Immunol 2021; 17:39. [PMID: 33865434 PMCID: PMC8052813 DOI: 10.1186/s13223-021-00544-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 04/07/2021] [Indexed: 01/12/2023] Open
Abstract
Backgrounds Chronic urticaria is a common disorder of the skin, characterised by recurrent skin wheals and angioedema. Recent reports have shown that altered diversity and composition of the gut microbiota may lead to imbalances in immune regulation, a causal factor in the occurrence of chronic urticaria. Objective This study aimed to evaluate the efficacy of the Yimingjia® probiotic formula in the adjuvant treatment of chronic urticaria in children. Methods We enrolled 206 children with confirmed diagnoses of chronic urticaria and randomly assigned them to the treatment (n = 104) or placebo group (n = 102). The children in each group were treated with desloratadine dry suspension, and those in the treatment group also received Yimingjia®. Clinical efficacy was evaluated at 1, 2 and 4 weeks. Results Clinical symptom scores did not differ significantly at weeks 1 and 2 (p > 0.05), but at 4 weeks, wheal size and attack frequency were significantly reduced in the treatment group (p = 0.049 and 0.03, respectively). The overall response rate (significant improvement + complete response) significantly differed between the treatment (80.8%) and placebo groups (62.5%) (χ2 = 4.20, p = 0.04). Conclusion Adjunct therapy with Yimingjia® was safe and effective at 4 weeks in the treatment of chronic urticaria in children. The study was registered under trial number NCT03328897.
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Affiliation(s)
- Xiao-Dong Bi
- Department of Dermatology, Nanyang First People's Hospital, Nanyang, 411300, Henan, China.
| | - Bao-Zhen Lu
- Department of Dermatology, Nanyang First People's Hospital, Nanyang, 411300, Henan, China
| | - Xin-Xin Pan
- Department of Dermatology, Nanyang First People's Hospital, Nanyang, 411300, Henan, China
| | - Sha Liu
- Department of Dermatology, Nanyang First People's Hospital, Nanyang, 411300, Henan, China
| | - Jiu-Yao Wang
- Centre for Allergy and Clinical Immunology Research (ACIR), College of Medicine, National Cheng Kung University, Tainan, Taiwan. .,Children's Hospital, China Medical University, Taichung, Taiwan. .,Department of Pediatrics, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan, 70428, Taiwan.
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Association of Allergic Diseases and Related Conditions with Dietary Fiber Intake in Korean Adults. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18062889. [PMID: 33808963 PMCID: PMC7998737 DOI: 10.3390/ijerph18062889] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022]
Abstract
An association between fiber intake and allergic diseases in children has been reported; however, many studies have not been conducted to assess this association in adults. We aimed to evaluate the association between dietary fiber intake and allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) among 10,479 adults using data from the Korean National Health and Nutrition Examination Survey (2010–2011). As dietary fiber intake increased, the prevalence of asthma (Q4 adjusted odds ratio (OR): 0.656; 95% confidence interval (CI): 0.48–0.91, p for trend < 0.0001) and atopic dermatitis (Q3 crude OR: 0.746; 95% CI: 0.57–0.98; Q4 adjusted OR: 0.712; 95% CI: 0.50–1.01, p for trend < 0.0001) decreased. The prevalence of allergic rhinitis (Q2 adjusted OR: 0.840; 95% CI: 0.70–1.00, p for trend < 0.0001) tended to decrease, especially in males. Subgroup analysis revealed that fiber intake reduced allergic rhinitis symptoms, including watery rhinorrhea (Q3 adjusted OR: 0.734; 95% CI: 0.55–0.97; Q4 adjusted OR: 0.722; 95% CI: 0.54–0.97) and dog allergen sensitization (Q3 adjusted OR: 0.319; 95% CI: 0.13–0.82; Q4 adjusted OR: 0.338; 95% CI: 0.13–0.86), exclusively in males. Thus, dietary fiber intake influences allergic diseases in adults, especially males.
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48
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Hua JL, Hu WP, Zuo YH, Zhang J. Prevention of Acute Exacerbation in Subjects with Moderate-to-very Severe COPD by Modulating Lower Respiratory Microbiome: Protocol of a Prospective, Multicenter, Randomized Controlled Trial. Int J Chron Obstruct Pulmon Dis 2020; 15:2985-2990. [PMID: 33235447 PMCID: PMC7680162 DOI: 10.2147/copd.s274005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 10/26/2020] [Indexed: 11/23/2022] Open
Abstract
Background COPD is a global respiratory disease that has produced a worldwide health care burden. Acute exacerbation of COPD (AECOPD) is the leading cause of death in patients with COPD and accounts for the majority of expenditure of COPD management. The colonization of potential pathogenic bacteria in the lower respiratory tract is an important cause of the acute exacerbation especially in patients with moderate and severe COPD. Some clinical studies have shown the potential of oral probiotics, aerosol-inhaled amikacin and combined vaccination to prevent AECOPD. Methods and Analysis We hypothesize that patients with stable COPD will benefit from aerosol-inhaled amikacin, oral probiotics or combined vaccination in terms of preventing acute exacerbation of COPD, slowing the progression of the disease and improving their quality of life. The trial aimsto investigate the efficacy and safety of the above interventions to decolonize bacteria in the lower respiratory tract and prevent acute exacerbation of COPD. In the study, 144 patients with stable phase of moderate-to-very severe COPD will be recruited and randomized into aerosol-inhaled amikacin group, oral probiotics group, combined vaccination group and the control group at a 1:1:1:1 ratio. The primary outcome is time to the first COPD exacerbation. Other endpoints include colonization of potential pathogenic bacteria in induced sputum, microbiome in induced sputum, pulmonary function and symptoms of patients, inflammation level and adverse events, serious adverse events, and death.
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Affiliation(s)
- Jian-Lan Hua
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Wei-Ping Hu
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Yi-Hui Zuo
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Jing Zhang
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
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Liu J, Ran Z, Wang F, Xin C, Xiong B, Song Z. Role of pulmonary microorganisms in the development of chronic obstructive pulmonary disease. Crit Rev Microbiol 2020; 47:1-12. [PMID: 33040638 DOI: 10.1080/1040841x.2020.1830748] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic obstructive respiratory disease characterized by irreversible airway limitation and persistent respiratory symptoms. The main clinical symptoms of COPD are dyspnoea, chronic cough, and sputum. COPD is often accompanied by other respiratory diseases, which can cause worsening of the disease. COPD patients with dyspnoea and aggravation of cough and sputum symptoms represent acute exacerbations of COPD (AECOPD). There is mounting evidence suggesting that dysbiosis of pulmonary microbiota participates in the disease. However, investigations of dysbiosis of pulmonary microbiota and the disease are still in initial phases. To screen, diagnose, and treat this respiratory disease, integrating data from different studies can improve our understanding of the occurrence and development of COPD and AECOPD. In this review, COPD epidemiology and the primary triggering mechanism are explored. Emerging knowledge regarding the association of inflammation, caused by pulmonary microbiome imbalance, and changes in lung microbiome flora species involved in the development of the disease are also highlighted. These data will further our understanding of the pathogenesis of COPD and AECOPD and may yield novel strategies for the use of pulmonary microbiota as a potential therapeutic intervention.
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Affiliation(s)
- Jiexing Liu
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China
| | - Zhuonan Ran
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China
| | - Fen Wang
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, PR China
| | - Caiyan Xin
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, PR China
| | - Bin Xiong
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China
| | - Zhangyong Song
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, PR China.,Molecular Biotechnology Platform, Public Center of Experimental Technology, Southwest Medical University, Luzhou, PR China
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AlKhater SA. Dynamic Interplay Between Microbiota and Mucosal Immunity in Early Shaping of Asthma and its Implication for the COVID-19 Pandemic. J Asthma Allergy 2020; 13:369-383. [PMID: 33061464 PMCID: PMC7532070 DOI: 10.2147/jaa.s272705] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 09/06/2020] [Indexed: 12/11/2022] Open
Abstract
The crosstalk between host immunity and the external environment in the mucous membranes of the gastrointestinal and respiratory tracts in bronchial asthma has recently been scrutinized. There is compelling evidence that the microbiota at these sites may play an important role in the pathogenesis of this chronic airway disease. The appearance of bacteria early in life in the gut before dissemination to the airways plays a pivotal role in shaping mucosal immunity. Loss of microbial diversity or dysbiosis can result in aberrant immune-mediated inflammation and mucosal barrier disruption, which coincides clinically with the successive development of the "allergic march" in asthma. Microbial manipulation may be effective in curbing asthma development by indirectly preserving homeostatic epithelial barrier functions. The protective effects and mechanisms of immunity-microbiome crosstalk at mucosal sites require further investigation to identify therapeutic and preventive measures in asthma. This topical review aims to highlight new evidence that compromised epithelial barrier function, which results in deregulated crosstalk between the microbiome and host mucosal immune system, is an important disease mechanism in asthma. In the light of current COVID-19 pandemic, the collective findings on the impact of mucosal microbiota on the suceptibility to SARS-CoV-2 infection and severity of COVID-19 is explored. The possible therapeutic implications to target these abnormalities are further discussed.
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Affiliation(s)
- Suzan A AlKhater
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Pediatrics, King Fahad Hospital of the University, Al-Khobar, Saudi Arabia
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