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Yang S, Qiao J, Zhang M, Kwok LY, Matijašić BB, Zhang H, Zhang W. Prevention and treatment of antibiotics-associated adverse effects through the use of probiotics: A review. J Adv Res 2025; 71:209-226. [PMID: 38844120 DOI: 10.1016/j.jare.2024.06.006] [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: 01/22/2024] [Revised: 05/18/2024] [Accepted: 06/03/2024] [Indexed: 06/29/2024] Open
Abstract
BACKGROUND The human gut hosts a diverse microbial community, essential for maintaining overall health. However, antibiotics, commonly prescribed for infections, can disrupt this delicate balance, leading to antibiotic-associated diarrhea, inflammatory bowel disease, obesity, and even neurological disorders. Recognizing this, probiotics have emerged as a promising strategy to counteract these adverse effects. AIM OF REVIEW This review aims to offer a comprehensive overview of the latest evidence concerning the utilization of probiotics in managing antibiotic-associated side effects. KEY SCIENTIFIC CONCEPTS OF REVIEW Probiotics play a crucial role in preserving gut homeostasis, regulating intestinal function and metabolism, and modulating the host immune system. These mechanisms serve to effectively alleviate antibiotic-associated adverse effects and enhance overall well-being.
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Affiliation(s)
- Shuwei Yang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Huhhot 010018, China
| | - Jiaqi Qiao
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Huhhot 010018, China
| | - Meng Zhang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Huhhot 010018, China
| | - Lai-Yu Kwok
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Huhhot 010018, China
| | | | - Heping Zhang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Huhhot 010018, China
| | - Wenyi Zhang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Huhhot 010018, China.
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Goh RCW, Maharajan MK, Gopinath D, Fang CM. The Therapeutic Effects of Probiotic on Systemic Lupus Erythematosus in Lupus Mice Models: A Systematic Review. Probiotics Antimicrob Proteins 2025; 17:35-50. [PMID: 38806966 DOI: 10.1007/s12602-024-10297-1] [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] [Accepted: 05/18/2024] [Indexed: 05/30/2024]
Abstract
Increasing evidence suggests the beneficial immunomodulatory effects of probiotics can reduce inflammation in systemic lupus erythematosus (SLE). However, there is no summary of the existing evidence available. This study aims to investigate the therapeutic effects of probiotics on SLE in a lupus mouse model by examining various markers, including inflammatory cytokines, Treg cells, disease activity, and gut microbiota. A systematic search was conducted using three databases (Web of Science, PubMed, and Scopus) to identify animal studies that reported the therapeutic benefits of probiotics against SLE. Data extracted from the selected articles were qualitatively synthesized. The SYRCLE risk of bias tool was used to evaluate the risk of bias. Out of a total of 3205 articles, 12 met the inclusion criteria. Probiotic strains, quantities, and routes of administration varied among the studies. The treatment ranged from 8 to 47 weeks. Probiotic strains such as L. fermentum CECT5716, L. casei B255, L. reuteri DSM 17509, L. plantarum LP299v, and L. acidophilus can significantly reduce pro-inflammatory cytokines (TNF-α, IL-12, IL-6, IL-1β, IL-17, and IFN-γ) levels while increasing anti-inflammatory IL-10 and Treg cells. Probiotics also delay the production of autoantibodies, thus prolonging the remission period, decreasing flare frequency, and delaying disease progression. Furthermore, probiotic administration prevents gut dysbiosis, increases intestinal stability, and prevents pathogen colonization. In conclusion, probiotics can be considered a new alternative therapeutic approach for the management of SLE. Further clinical studies are required to investigate and validate the safety and effectiveness of probiotics in humans.
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Affiliation(s)
- Rachael Chaeh-Wen Goh
- Division of Biomedical Sciences, School of Pharmacy, University of Nottingham Malaysia, Jalan Broga, 43500, Semenyih, Malaysia
| | - Mari Kannan Maharajan
- School of Pharmacy, University of Nottingham Malaysia, Jalan Broga, 43500, Semenyih, Malaysia
| | - Divya Gopinath
- Basic Medical and Dental Sciences Department, College of Dentistry, Ajman University, P.O. Box 346, Ajman, United Arab Emirates
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Chee-Mun Fang
- Division of Biomedical Sciences, School of Pharmacy, University of Nottingham Malaysia, Jalan Broga, 43500, Semenyih, Malaysia.
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Quansah M, David MA, Martins R, El-Omar E, Aliberti SM, Capunzo M, Jensen SO, Tayebi M. The Beneficial Effects of Lactobacillus Strains on Gut Microbiome in Alzheimer's Disease: A Systematic Review. Healthcare (Basel) 2025; 13:74. [PMID: 39791681 PMCID: PMC11720007 DOI: 10.3390/healthcare13010074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/31/2024] [Accepted: 12/31/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND/OBJECTIVES Growing evidence suggests that the gut-brain axis influences brain function, particularly the role of intestinal microbiota in modulating cognitive processes. Probiotics may alter brain function and behavior by modulating gut microbiota, with implications for neurodegenerative diseases like Alzheimer's disease (AD). The purpose of this review is to systematically review the current literature exploring the effects of probiotic supplementation on gut microbiota and cognitive function in AD and mild cognitive impairment (MCI). METHODS A comprehensive literature search was conducted across PubMed/Medline, Embase, and Scopus to identify relevant randomized controlled trials (RCTs) from inception to 20 August 2024. The search focused on comparing outcomes between intervention and control/placebo groups. Data searches, article selection, data extraction, and risk of bias assessment were performed in accordance with Cochrane guidelines. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no: CRD42023446796. RESULTS Data from four RCTs involving 293 Individuals (AD and MCI patients) receiving mainly Lactobacillus and Bifidobacterium strains showed some beneficial effects on cognitive function, altered gut microbiota composition, and positively affected metabolic biomarkers. However, variability in microbiota assessment across studies limits the interpretation of results. The limited number and quality of the existing studies make it difficult to draw definitive conclusions from the data. Additional high-quality research is clearly needed. CONCLUSIONS Probiotics show promise as an adjunctive intervention for cognitive decline, but larger, long-term trials are needed to confirm their efficacy and clinical applicability in neurodegenerative diseases like AD.
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Affiliation(s)
- Michael Quansah
- Neuroimmunology Laboratory, School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (M.Q.); (M.A.D.)
- Department of Medicine and Therapeutics, Medical School, University of Ghana, Accra LG25, Ghana
| | - Monique Antoinette David
- Neuroimmunology Laboratory, School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (M.Q.); (M.A.D.)
| | - Ralph Martins
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia;
| | - Emad El-Omar
- Microbiome Research Centre, School of Clinical Medicine, UNSW Medicine & Health, St George & Sutherland Clinical Campuses, UNSW, Kogarah, NSW 2217, Australia;
| | - Silvana Mirella Aliberti
- Hygiene and Preventive Medicine Section, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, 84081 Salerno, Italy; (S.M.A.); (M.C.)
| | - Mario Capunzo
- Hygiene and Preventive Medicine Section, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, 84081 Salerno, Italy; (S.M.A.); (M.C.)
| | - Slade O. Jensen
- School of Medicine, Microbiology and Infectious Diseases, Ingham Institute for Applied Medical Research, Western Sydney University, Liverpool, NSW 1871, Australia;
| | - Mourad Tayebi
- Neuroimmunology Laboratory, School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (M.Q.); (M.A.D.)
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Bravo M, Gonçalves P, García-Jiménez W, Montero MJ, Cerrato R, Fernández-Llario P, Risco D. Effect of Lactic Acid Bacteria-Derived Postbiotic Supplementation on Tuberculosis in Wild Boar Populations. Pathogens 2024; 13:1078. [PMID: 39770338 PMCID: PMC11728476 DOI: 10.3390/pathogens13121078] [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: 10/20/2024] [Revised: 11/22/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025] Open
Abstract
The Eurasian wild boar (Sus scrofa) is a key wildlife host for tuberculosis (TB) in central and southwestern Spain, posing a challenge to TB eradication in livestock. New strategies, including the use of beneficial microbes, are being explored to mitigate wildlife diseases. This study evaluated the effect of oral supplementation with postbiotic antimycobacterial metabolites produced using Ingulados' lactic acid bacteria (LAB) collection on TB development in wild boar. A total of 20 game estates in mid-western Spain were divided into two groups: one fed with standard feed containing the postbiotic product and a control group fed without postbiotics. Data were collected from wild boar during hunting events pre- and post-supplementation. The presence of TB-like lesions (TBLLs), lesion severity and seropositivity against Mycobacterium bovis were assessed. Postbiotic supplementation led to a 36.87% reduction in TBLLs and a 35.94% decrease in seropositivity. Notably, young wild boar showed a 64.72% reduction in TBLLs and an 81.80% drop in seropositivity, suggesting reduced transmission. These findings support the potential of postbiotics as a safe, feasible and sustainable tool to control TB in wild boar, offering a promising addition to broader TB eradication efforts.
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Affiliation(s)
- Maria Bravo
- Ingulados S.L., Calle Miguel Servet 13, 10003 Cáceres, Spain; (M.B.); (P.G.); (W.G.-J.); (M.J.M.); (R.C.); (P.F.-L.)
| | - Pilar Gonçalves
- Ingulados S.L., Calle Miguel Servet 13, 10003 Cáceres, Spain; (M.B.); (P.G.); (W.G.-J.); (M.J.M.); (R.C.); (P.F.-L.)
| | - Waldo García-Jiménez
- Ingulados S.L., Calle Miguel Servet 13, 10003 Cáceres, Spain; (M.B.); (P.G.); (W.G.-J.); (M.J.M.); (R.C.); (P.F.-L.)
- Unidad de Histología y Anatomía Patológica, Departamento de Medicina Animal, Veterinary Faculty, University of Cáceres, Avenida de la Universidad s/n, 10003 Cáceres, Spain
| | - María José Montero
- Ingulados S.L., Calle Miguel Servet 13, 10003 Cáceres, Spain; (M.B.); (P.G.); (W.G.-J.); (M.J.M.); (R.C.); (P.F.-L.)
| | - Rosario Cerrato
- Ingulados S.L., Calle Miguel Servet 13, 10003 Cáceres, Spain; (M.B.); (P.G.); (W.G.-J.); (M.J.M.); (R.C.); (P.F.-L.)
| | - Pedro Fernández-Llario
- Ingulados S.L., Calle Miguel Servet 13, 10003 Cáceres, Spain; (M.B.); (P.G.); (W.G.-J.); (M.J.M.); (R.C.); (P.F.-L.)
| | - David Risco
- Unidad de Histología y Anatomía Patológica, Departamento de Medicina Animal, Veterinary Faculty, University of Cáceres, Avenida de la Universidad s/n, 10003 Cáceres, Spain
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Alexander LM, Khalid S, Gallego-Lopez GM, Astmann TJ, Oh JH, Heggen M, Huss P, Fisher R, Mukherjee A, Raman S, Choi IY, Smith MN, Rogers CJ, Epperly MW, Knoll LJ, Greenberger JS, van Pijkeren JP. Development of a Limosilactobacillus reuteri therapeutic delivery platform with reduced colonization potential. Appl Environ Microbiol 2024; 90:e0031224. [PMID: 39480094 DOI: 10.1128/aem.00312-24] [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: 02/20/2024] [Accepted: 09/09/2024] [Indexed: 11/02/2024] Open
Abstract
Bacterial biotherapeutic delivery vehicles have the potential to treat a variety of diseases. This approach obviates the need to purify the recombinant effector molecule, allows delivery of therapeutics in situ via oral or intranasal administration, and protects the effector molecule during gastrointestinal transit. Lactic acid bacteria have been broadly developed as therapeutic delivery vehicles though risks associated with the colonization of a genetically modified microorganism have so-far not been addressed. Here, we present an engineered Limosilactobacillus reuteri strain with reduced colonization potential. We applied a dual-recombineering scheme for efficient barcoding and generated mutants in genes encoding five previously characterized and four uncharacterized putative adhesins. Compared with the wild type, none of the mutants were reduced in their ability to survive gastrointestinal transit in mice. CmbA was identified as a key protein in L. reuteri adhesion to HT-29 and enteroid cells. The nonuple mutant, a single strain with all nine genes encoding adhesins inactivated, had reduced capacity to adhere to enteroid monolayers. The nonuple mutant producing murine IFN-β was equally effective as its wild-type counterpart in mitigating radiation toxicity in mice. Thus, this work established a novel therapeutic delivery platform that lays a foundation for its application in other microbial therapeutic delivery candidates and furthers the progress of the L. reuteri delivery system towards human use.IMPORTANCEOne major advantage to leverage gut microbes that have co-evolved with the vertebrate host is that evolution already has taken care of the difficult task to optimize survival within a complex ecosystem. The availability of the ecological niche will support colonization. However, long-term colonization of a recombinant microbe may not be desirable. Therefore, strategies need to be developed to overcome this potential safety concern. In this work, we developed a single strain in which we inactivated the encoding sortase, and eight genes encoding characterized/putative adhesins. Each individual mutant was characterized for growth and adhesion to epithelial cells. On enteroid cells, the nonuple mutant has a reduced adhesion potential compared with the wild-type strain. In a model of total-body irradiation, the nonuple strain engineered to release murine interferon-β performed comparable to a derivative of the wild-type strain that releases interferon-β. This work is an important step toward the application of recombinant L. reuteri in humans.
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Affiliation(s)
- Laura M Alexander
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Saima Khalid
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Gina M Gallego-Lopez
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Morgridge Institute for Research, Madison, Wisconsin, USA
| | - Theresa J Astmann
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Jee-Hwan Oh
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Mark Heggen
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Phil Huss
- Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Renee Fisher
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - Amitava Mukherjee
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - Srivatsan Raman
- Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - In Young Choi
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Morgan N Smith
- Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | | | - Michael W Epperly
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - Laura J Knoll
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Joel S Greenberger
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
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Akinosoglou K, Schinas G, Polyzou E, Tsiakalos A, Donders GGG. Probiotics in the Management of Vulvovaginal Candidosis. J Clin Med 2024; 13:5163. [PMID: 39274376 PMCID: PMC11396221 DOI: 10.3390/jcm13175163] [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: 07/07/2024] [Revised: 08/26/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Vulvovaginal candidosis (VVC) represents a frequent and cumbersome vaginal infection. Recurrent and/or persistent infections remain common among a significant number of patients despite the use of antifungals. Probiotics offer a promising adjunctive or alternative therapeutic strategy to antifungals in the management of VVC. We aimed to explore and thoroughly examine the various roles and potential applications of probiotics in VVC. A comprehensive literature search was conducted to identify relevant clinical trials and systematic reviews that examine the effectiveness of probiotics in the treatment and prevention of VVC and recurrent VVC (rVVC). Following the initial screening of 4563 articles, a total of 25 clinical studies and seven systematic reviews were finally included in this analysis. The studies reviewed provide a generally positive yet inconsistent view of the efficacy of probiotics in managing VVC, including clinical, mycological response, and prevention perspectives. Nonetheless, fluconazole remains more effective than probiotics in treating VVC, while the combination of the two seems to reduce recurrence and improve symptoms significantly. For prevention, probiotics seem to improve vaginal health and reduce symptoms, while safety and tolerability are consistently reported across the studies, affirming that probiotics represent a low-risk intervention. However, clear conclusions are difficult to establish since relative studies explore different clinical endpoints and follow-up times, variable populations are included, different probiotics are used, and diverse schedules and regimens are administered. We propose that future studies should study the benefit of probiotics in well-defined categories such as (1) treatment with acute probiotics instead of antifungals, (2) adjuvant probiotic therapy together or after antifungals, and (3) VVC recurrence prevention using probiotics.
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Affiliation(s)
- Karolina Akinosoglou
- Department of Medicine, University of Patras, 26504 Rio, Greece
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, 26504 Rio, Greece
| | | | - Eleni Polyzou
- Department of Medicine, University of Patras, 26504 Rio, Greece
| | | | - Gilbert G G Donders
- Femicare, Clinical Research for Women, 3300 Tienen, Belgium
- University Hospital Antwerpen, 2650 Antwerp, Belgium
- Department of Obstetrics and Gynecology, Regional Hospital Heilig Hart, 3000 Tienen, Belgium
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Zhang Z, Zhang HL, Yang DH, Hao Q, Yang HW, Meng DL, Meindert de Vos W, Guan LL, Liu SB, Teame T, Gao CC, Ran C, Yang YL, Yao YY, Ding QW, Zhou ZG. Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects. IMETA 2024; 3:e181. [PMID: 38882496 PMCID: PMC11170971 DOI: 10.1002/imt2.181] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 02/22/2024] [Accepted: 02/26/2024] [Indexed: 06/18/2024]
Abstract
Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.
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Affiliation(s)
- Zhen Zhang
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
- Faculty of Land and Food Systems The University of British Columbia Vancouver Canada
| | - Hong-Ling Zhang
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Da-Hai Yang
- State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai China
| | - Qiang Hao
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Hong-Wei Yang
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - De-Long Meng
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Willem Meindert de Vos
- Laboratory of Microbiology Wageningen University and Research Wageningen Netherlands
- Human Microbiome Research Program, Faculty of Medicine University of Helsinki Helsinki Finland
| | - Le-Luo Guan
- Faculty of Land and Food Systems The University of British Columbia Vancouver Canada
| | - Shu-Bin Liu
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Tsegay Teame
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
- Tigray Agricultural Research Institute Mekelle Ethiopia
| | - Chen-Chen Gao
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Chao Ran
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Ya-Lin Yang
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Yuan-Yuan Yao
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Qian-Wen Ding
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
| | - Zhi-Gang Zhou
- China-Norway Joint Lab on Fish Gut Microbiota, Institute of Feed Research Chinese Academy of Agricultural Sciences Beijing China
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8
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Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis. Life (Basel) 2023; 13:life13020561. [PMID: 36836917 PMCID: PMC9959300 DOI: 10.3390/life13020561] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/31/2023] [Accepted: 02/15/2023] [Indexed: 02/19/2023] Open
Abstract
Short chain fatty acids (SCFAs), the principle end-products produced by the anaerobic gut microbial fermentation of complex carbohydrates (CHO) in the colon perform beneficial roles in metabolic health. Butyrate, acetate and propionate are the main SCFA metabolites, which maintain gut homeostasis and host immune responses, enhance gut barrier integrity and reduce gut inflammation via a range of epigenetic modifications in DNA/histone methylation underlying these effects. The infant gut microbiota composition is characterized by higher abundances of SCFA-producing bacteria. A large number of in vitro/vivo studies have demonstrated the therapeutic implications of SCFA-producing bacteria in infant inflammatory diseases, such as obesity and asthma, but the application of gut microbiota and its metabolite SCFAs to necrotizing enterocolitis (NEC), an acute inflammatory necrosis of the distal small intestine/colon affecting premature newborns, is scarce. Indeed, the beneficial health effects attributed to SCFAs and SCFA-producing bacteria in neonatal NEC are still to be understood. Thus, this literature review aims to summarize the available evidence on the therapeutic potential of gut microbiota and its metabolite SCFAs in neonatal NEC using the PubMed/MEDLINE database.
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The Potential Therapeutic Role of Lactobacillaceae rhamnosus for Treatment of Inflammatory Bowel Disease. Foods 2023; 12:foods12040692. [PMID: 36832767 PMCID: PMC9955806 DOI: 10.3390/foods12040692] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/26/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a heterogeneous group of diseases associated with chronic inflammation of the intestinal tract, and is highly prevalent worldwide. Although its origin is not yet fully understood, new evidence emphasizes that environmental factors, especially dietary factors and intestinal microbiota disorders are key triggers of IBD. Probiotics, such as Lactobacillaceae spp., play an essential role in human health as they exert beneficial effects on the composition of the human gastrointestinal microbial community and immune system. Probiotic-based therapies have been shown to be effective in alleviating IBD. Among these, Lactobacillaceae rhamnosus is one of the most widely used strains. L. rhamnosus is widely present in the intestines of healthy individuals; it regulates the intestinal immune system and reduces inflammation through a variety of mechanisms. The purpose of this study was to identify scientific evidence related to L. rhamnosus and IBD, review and summarize the results, and discuss the possible mechanisms of action as a starting point for future research on IBD treatment.
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10
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Yang Z, Liu X, Wu Y, Peng J, Wei H. Effect of the Microbiome on Intestinal Innate Immune Development in Early Life and the Potential Strategy of Early Intervention. Front Immunol 2022; 13:936300. [PMID: 35928828 PMCID: PMC9344006 DOI: 10.3389/fimmu.2022.936300] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/23/2022] [Indexed: 12/15/2022] Open
Abstract
Early life is a vital period for mammals to be colonized with the microbiome, which profoundly influences the development of the intestinal immune function. For neonates to resist pathogen infection and avoid gastrointestinal illness, the intestinal innate immune system is critical. Thus, this review summarizes the development of the intestinal microbiome and the intestinal innate immune barrier, including the intestinal epithelium and immune cells from the fetal to the weaning period. Moreover, the impact of the intestinal microbiome on innate immune development and the two main way of early-life intervention including probiotics and fecal microbiota transplantation (FMT) also are discussed in this review. We hope to highlight the crosstalk between early microbial colonization and intestinal innate immunity development and offer some information for early intervention.
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Affiliation(s)
- Zhipeng Yang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Xiangchen Liu
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Yanting Wu
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Jian Peng
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
- The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China
| | - Hongkui Wei
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
- The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China
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11
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Sanborn V, Aljumaah M, Azcarate-Peril MA, Gunstad J. Examining the cognitive benefits of probiotic supplementation in physically active older adults: A randomized clinical trial. Appl Physiol Nutr Metab 2022; 47:871-882. [PMID: 35617704 DOI: 10.1139/apnm-2021-0557] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The prevalence of dementia is projected to increase with the growing older adult population and prevention strategies are urgently needed. Two promising interventions include physical activity (PA) and probiotic supplementation, with initial findings suggesting their combined use may confer greater cognitive benefits than either intervention alone. However, no study has yet examined the effects of probiotic supplementation on cognitive function in healthy, physically active older adults. The present study used archival data from a randomized clinical trial including 127 physically active, middle-aged to older adults (avg age 64.3 years) with self-reported PA levels meeting or exceeding recommendations to investigate the effects of probiotic supplementation (Lactobacillus rhamnosus GG; L.GG) on cognitive outcomes. Repeated measures ANOVAs showed no significant changes in cognitive performance from baseline to follow up as an effect of L.GG consumption. These results suggest that probiotic supplementation may not improve cognitive function in persons already engaged in high levels of PA. Future research should include prospective studies to determine whether long-term use of probiotic supplementation may help prevent cognitive decline. Novelty: • Initial research shows promising cognitive benefits of combined physical activity and probiotics consumption. • L.GG did not lead to acute cognitive improvements for older adults already meeting physical activity guidelines. • Prospective studies examining prevention of cognitive decline with probiotics in healthy and clinical samples are much needed.
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Affiliation(s)
- Victoria Sanborn
- Kent State University, 4229, Psychological Sciences, 600 Hilltop Drive, Kent, Ohio, United States, 44242;
| | - Mashael Aljumaah
- University of North Carolina System, 2332, Department of Medicine, and UNC Microbiome Core, Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, School of Medicine, Chapel Hill, North Carolina, United States.,North Carolina State University at Raleigh, 6798, Department of Plant and Microbial Biology, Raleigh, North Carolina, United States;
| | - M Andrea Azcarate-Peril
- University of North Carolina at Chapel Hill School of Medicine, 6797, Department of Medicine, and UNC Microbiome Core, Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina, United States;
| | - John Gunstad
- Kent State University College of Arts and Sciences, 142731, Psychological Sciences; Brain Health Research Institute, Kent, Ohio, United States;
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12
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Post SE, Brito IL. Structural insight into protein-protein interactions between intestinal microbiome and host. Curr Opin Struct Biol 2022; 74:102354. [PMID: 35390637 DOI: 10.1016/j.sbi.2022.102354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/27/2022] [Accepted: 02/06/2022] [Indexed: 11/03/2022]
Abstract
Protein-protein interactions between the microbiome and host organism play an important role in shaping host health. These host-modulating proteins have therapeutic potential in treating microbiome-linked disorders such as inflammatory bowel disease and obesity. Structural analysis of interacting proteins provides highly mechanistic insight into the domains driving these interactions and the resulting influence on host cell processes. Here, we briefly review recent publication of microbiome protein structures involved in host binding interactions, the effects of these interactions on host physiology, and the need for further study to increase the ability to detect proteins with therapeutic potential.
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Affiliation(s)
- Sarah E Post
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA. https://twitter.com/@sarahpost140
| | - Ilana L Brito
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
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13
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Li X, Wang Q, Hu X, Liu W. Current Status of Probiotics as Supplements in the Prevention and Treatment of Infectious Diseases. Front Cell Infect Microbiol 2022; 12:789063. [PMID: 35360101 PMCID: PMC8964067 DOI: 10.3389/fcimb.2022.789063] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 02/03/2022] [Indexed: 12/20/2022] Open
Abstract
Probiotics play an important role against infectious pathogens via their effects on the epithelium, the production of antimicrobial compounds, and competitive exclusion. Administration of probiotic supplements may reduce the risk of infectious diseases and the use of antibiotics, hence contributing to a reduction or a delay of the development of multi-resistant bacteria. Infection is a constant concern for people who experience recurrent infections, and antibiotic treatment usually fails due to antibiotic resistance. Therefore, an infection can lead to severe illness and hospitalization if left untreated. A growing number of studies have demonstrated promising results for a variety of probiotic strains used to prevent or treat acute and recurrent infectious diseases, but additional standardized clinical research is needed.
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Affiliation(s)
| | - Qiang Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan, China
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14
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Beterams A, De Paepe K, Maes L, Wise IJ, De Keersmaecker H, Rajkovic A, Laukens D, Van de Wiele T, Calatayud Arroyo M. Versatile human in vitro triple coculture model coincubated with adhered gut microbes reproducibly mimics pro-inflammatory host-microbe interactions in the colon. FASEB J 2021; 35:e21992. [PMID: 34719821 DOI: 10.1096/fj.202101135r] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/23/2021] [Accepted: 10/01/2021] [Indexed: 12/21/2022]
Abstract
The colonic epithelial barrier is vital to preserve gut and host health by maintaining the immune homeostasis between host and microbes. The mechanisms underlying beneficial or harmful host-microbe interactions are poorly understood and impossible to study in vivo given the limited accessibility and ethical constraints. Moreover, existing in vitro models lack the required cellular complexity for the routine, yet profound, analysis of the intricate interplay between different types of host and microbial cells. We developed and characterized a broadly applicable, easy-to-handle in vitro triple coculture model that combines chemically-induced macrophage-like, goblet and epithelial cells covered by a mucus layer, which can be coincubated with complex human-derived gut microbiota samples for 16 h. Comparison with a standard epithelial monolayer model revealed that triple cocultures produce thicker mucus layers, morphologically organize in a network and upon exposure to human-derived gut microbiota samples, respond via pro-inflammatory cytokine production. Both model systems, however, were not suffering from cytotoxic stress or different microbial loads, indicating that the obtained endpoints were caused by the imposed conditions. Addition of the probiotic Lactobacillus rhamnosus GG to assess its immunomodulating capacity in the triple coculture slightly suppressed pro-inflammatory cytokine responses, based on transcriptomic microarray analyses. TNF conditioning of the models prior to microbial exposure did not cause shifts in cytokines, suggesting a strong epithelial barrier in which TNF did not reach the basolateral side. To conclude, the triple coculture model is tolerable towards manipulations and allows to address mechanistic host-microbe research questions in a stable in vitro environment.
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Affiliation(s)
- Annelore Beterams
- Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium
| | - Kim De Paepe
- Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium
| | - Laure Maes
- Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium.,Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - India Jane Wise
- Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium
| | | | - Andreja Rajkovic
- Laboratory of Food Microbiology and Food Preservation, Ghent University, Ghent, Belgium
| | - Debby Laukens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Tom Van de Wiele
- Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium
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15
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A Pilot Study To Establish an In Vitro Model To Study Premature Intestinal Epithelium and Gut Microbiota Interactions. mSphere 2021; 6:e0080621. [PMID: 34643422 PMCID: PMC8513685 DOI: 10.1128/msphere.00806-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Intestinal microbiota has emerged as an important player in the health and disease of preterm infants. The interactions between intestinal flora and epithelium can lead to local injury and systemic diseases. A suitable in vitro cell model is needed to enhance our understanding of these interactions. In this study, we exposed fetal epithelial cell cultures (FHs-74 int cells, human, ATCC CCL 241) to sterile fecal filtrates derived from stool collected from preterm infants at <2 and at 3 to 4 weeks of age. We measured the cytokine levels from the culture media after 4, 24, and 48 h of exposure to the fecal filtrates. We analyzed the 16S rRNA V4 gene data of the fecal samples and transcriptome sequencing (RNA-seq) data from the fetal epithelial cells after 48 h of exposure to the same fecal filtrates. The results showed correlations between inflammatory responses (both cytokine levels and gene expression) and the Proteobacteria-to-Firmicutes ratio and between fecal bacterial genera and epithelial apoptosis-related genes. Our in vitro cell model can be further developed and applied to study how the epithelium responds to different microbial flora from preterm infants. Combining immature epithelial cells and preterm infant stool samples into one model allows us to investigate disease processes in preterm infants in a way that had not been previously reported. IMPORTANCE The gut bacterial flora influences the development of the immune system and long-term health outcomes in preterm infants. Studies of the mechanistic interactions between the gut bacteria and mucosal barrier are limited to clinical observations, animal models, and in vitro cell culture models for this vulnerable population. Most in vitro cell culture models of microbe-host interactions use single organisms or adult origin cell lines. Our study is innovative and significant in that we expose immature epithelial cells derived from fetal tissues to fecal filtrates from eight stool samples from four preterm infants to study the role of intestinal epithelial cells. In addition, we analyzed epithelial gene expression to examine multiple cellular processes simultaneously. This model can be developed into patient-derived two- or three-dimensional cell cultures exposed to their own fecal material to allow better prediction of patient physiological responses to support the growing field of precision medicine.
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16
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Tan W, Zhou Z, Li W, Lu H, Qiu Z. Lactobacillus rhamnosus GG for Cow's Milk Allergy in Children: A Systematic Review and Meta-Analysis. Front Pediatr 2021; 9:727127. [PMID: 34746056 PMCID: PMC8569903 DOI: 10.3389/fped.2021.727127] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 09/20/2021] [Indexed: 12/13/2022] Open
Abstract
Objective: Cow's milk allergy (CMA) is a common allergic disease. Probiotics have been suggested as a treatment for CMA, with Lactobacillus rhamnosus GG (LGG) being one of the important predominant choices. Despite reports on this topic, the effectiveness of application in CMA remains to be firmly established. Methods: To assess the effects of LGG on CMA in children, the PubMed/Medline, Embase, Cochrane Library, and Web of Science databases were searched for studies on LGG in treatment of CMA, which were published in the English language. Results: Ten studies were finally included. Significantly higher tolerability rates favoring LGG over controls were observed [risk ratio (RR), 2.22; 95% confidence interval (CI), 1.86-2.66; I 2 = 0.00; moderate-quality evidence]. There were no significant differences in SCORAD values favoring LGG over the placebo (mean difference, 1.41; 95% CI, -4.99-7.82; p = 0.67; very low-quality evidence), and LGG may have improved fecal occult blood (risk ratio, 0.36; 95% CI, 0.14-0.92; p = 0.03; low-quality evidence). Conclusion: We found that LGG may have moderate-quality evidence to promote oral tolerance in children with CMA and may facilitate recovery from intestinal symptoms. However, this finding must be treated with caution, and more gpowerful RCTs are needed to evaluate the most effective dose and treatment time for children with CMA. Registration number: CRD42021237221.
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Affiliation(s)
- Weifu Tan
- Department of Pediatrics, Dongguan Binhaiwan Central Hospital, Jinan University, Dongguan, China
| | - Zhicong Zhou
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Wei Li
- Department of Pediatrics, Dongguan Binhaiwan Central Hospital, Jinan University, Dongguan, China
| | - Han Lu
- Department of Obstotrics and Gynocology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Zemin Qiu
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, China
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17
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Wildlife symbiotic bacteria are indicators of the health status of the host and its ecosystem. Appl Environ Microbiol 2021; 88:e0138521. [PMID: 34669453 PMCID: PMC8752132 DOI: 10.1128/aem.01385-21] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Lactic acid bacteria (LAB) are gut symbionts that can be used as a model to understand the host-microbiota crosstalk under unpredictable environmental conditions such as wildlife ecosystems. The aim of this study was to determine whether viable LAB can be informative of the health status of wild boar populations. We monitored the genotype and phenotype of LAB based on markers that included safety and phylogenetic origin, antibacterial activity and immunomodulatory properties. A LAB profile dominated by lactobacilli appears to stimulate protective immune responses and relates to strains widely used as probiotics, resulting in a potentially healthy wildlife population whereas microbiota overpopulated by enterococci was observed in a hostile environment. These enterococci were closely related to pathogenic strains that have developed mechanisms to evade innate immune system, posing a potential risk for the host health. Furthermore, our LAB isolates displayed antibacterial properties in a species-dependent manner. Nearly all of them were able to inhibit bacterial pathogens, raising the possibility of using them as a la carte antibiotic alternative in the unexplored field of wildlife disease mitigation. Our study highlights that microbiological characterization of LAB is a useful indicator of wildlife health status and the ecological origin from which they derive. Significance Statement The wildlife symbiotic microbiota is an important component to the greater for greater diversity and functionality of their bacterial populations, influencing the host health and adaptability to its ecosystem. Although many microbes are partly responsible for the development of multiple physiological processes, only certain bacterial groups such as lactic acid bacteria (LAB) have the capacity to overpopulate the gut, promoting health (or disease) when specific genetic and environmental conditions are present. LAB have been exploited in many ways due to their probiotic properties, in particular lactobacilli, however their relationship with wildlife gut-associated microbiota hosts remains to be elucidated. On the other hand, it is unclear whether LAB such as enterococci, which have been associated with detrimental health effects, could lead to disease. These important questions have not been properly addressed in the field of wildlife, and therefore, should be clearly attained.
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18
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Vazquez-Munoz R, Dongari-Bagtzoglou A. Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action. FRONTIERS IN ORAL HEALTH 2021; 2:689382. [PMID: 35048033 PMCID: PMC8757823 DOI: 10.3389/froh.2021.689382] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 06/21/2021] [Indexed: 12/15/2022] Open
Abstract
Lactobacilli are among the most studied bacteria in the microbiome of the orodigestive and genitourinary tracts. As probiotics, lactobacilli may provide various benefits to the host. These benefits include regulating the composition of the resident microbiota, preventing - or even potentially reverting- a dysbiotic state. Candida albicans is an opportunistic pathogen that can influence and be influenced by other members of the mucosal microbiota and, under immune-compromising conditions, can cause disease. Lactobacillus and Candida species can colonize the same mucosal sites; however, certain Lactobacillus species display antifungal activities that can contribute to low Candida burdens and prevent fungal infection. Lactobacilli can produce metabolites with direct anticandidal function or enhance the host defense mechanisms against fungi. Most of the Lactobacillus spp. anticandidal mechanisms of action remain underexplored. This work aims to comprehensively review and provide an update on the current knowledge regarding these anticandidal mechanisms.
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Affiliation(s)
- Roberto Vazquez-Munoz
- Department of Oral Health and Diagnostic Sciences, University of Connecticut Health Center, Farmington, CT, United States
| | - Anna Dongari-Bagtzoglou
- Department of Oral Health and Diagnostic Sciences, University of Connecticut Health Center, Farmington, CT, United States
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19
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Spangler JR, Caruana JC, Medintz IL, Walper SA. Harnessing the potential of Lactobacillus species for therapeutic delivery at the lumenal-mucosal interface. Future Sci OA 2021; 7:FSO671. [PMID: 33815818 PMCID: PMC8015674 DOI: 10.2144/fsoa-2020-0153] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Lactobacillus species have been studied for over 30 years in their role as commensal organisms in the human gut. Recently there has been a surge of interest in their abilities to natively and recombinantly stimulate immune activities, and studies have identified strains and novel molecules that convey particular advantages for applications as both immune adjuvants and immunomodulators. In this review, we discuss the recent advances in Lactobacillus-related activity at the gut/microbiota interface, the efforts to probe the boundaries of the direct and indirect therapeutic potential of these bacteria, and highlight the continued interest in harnessing the native capacity for the production of biogenic compounds shown to influence nervous system activity. Taken together, these aspects underscore Lactobacillus species as versatile therapeutic delivery vehicles capable of effector production at the lumenal-mucosal interface, and further establish a foundation of efficacy upon which future engineered strains can expand.
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Affiliation(s)
- Joseph R Spangler
- National Research Council Postdoctoral Fellow sited in US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA
| | - Julie C Caruana
- American Society for Engineering Education Postdoctoral Fellow sited in US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA
| | - Igor L Medintz
- US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA
| | - Scott A Walper
- US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA
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20
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Sanborn V, Azcarate-Peril MA, Updegraff J, Manderino L, Gunstad J. Randomized Clinical Trial Examining the Impact of Lactobacillus rhamnosus GG Probiotic Supplementation on Cognitive Functioning in Middle-aged and Older Adults. Neuropsychiatr Dis Treat 2020; 16:2765-2777. [PMID: 33223831 PMCID: PMC7671471 DOI: 10.2147/ndt.s270035] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/02/2020] [Indexed: 12/19/2022] Open
Abstract
PURPOSE The gut microbiome has been linked to cognitive function and appears to worsen with aging. Probiotic supplementation has been found to improve the health of the gut microbiome. As such, it is possible that probiotic supplementation may protect the aging brain. The current study examined the cognitive benefits of probiotic supplementation (Lactobacillus rhamnosus GG) in healthy middle-aged and older adults. MATERIALS AND METHODS The study was a double-blind, placebo-controlled, randomized clinical trial. Two hundred community-dwelling adults aged 52-75 were enrolled (mean age=64.3, SD=5.52). A three-month intervention involved daily consumption of probiotic or placebo. Independent sample t-tests, chi-squared tests, and repeated measure ANOVAs compared groups and examined changes over time. Primary outcome was change in NIH Toolbox Total Cognition Score from baseline to follow-up. RESULTS A total of 145 participants were examined in primary analyses (probiotic=77, placebo=68) and excluded persons due to discontinuation, low adherence, missing data, or outlier values. Established criteria (ie ≥1 subtest t-scores ≤35; n=19, n=23) were used to operationally define cognitive impairment. Repeated measures ANOVAs revealed that persons with cognitive impairment who consumed probiotics exhibited a greater total cognition score improvement than persons with cognitive impairment in the placebo group and cognitively intact persons in probiotic or placebo groups. CONCLUSION Lactobacillus rhamnosus GG probiotic supplementation was associated with improved cognitive performance in middle-aged and older adults with cognitive impairment. Probiotic supplementation may be a novel method for protecting cognitive health in aging.
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Affiliation(s)
- Victoria Sanborn
- Department of Psychological Sciences, Kent State University, Kent, OH, USA
| | - M Andrea Azcarate-Peril
- Department of Cell Biology and Physiology and Microbiome Core Facility, UNC School of Medicine, Chapel Hill, North Carolina, USA
| | - John Updegraff
- Department of Psychological Sciences, Kent State University, Kent, OH, USA
| | - Lisa Manderino
- Department of Psychological Sciences, Kent State University, Kent, OH, USA
| | - John Gunstad
- Department of Psychological Sciences, Kent State University, Kent, OH, USA
- Brain Health Research Institute, Kent State University, Kent, OH, USA
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21
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Teame T, Wang A, Xie M, Zhang Z, Yang Y, Ding Q, Gao C, Olsen RE, Ran C, Zhou Z. Paraprobiotics and Postbiotics of Probiotic Lactobacilli, Their Positive Effects on the Host and Action Mechanisms: A Review. Front Nutr 2020; 7:570344. [PMID: 33195367 PMCID: PMC7642493 DOI: 10.3389/fnut.2020.570344] [Citation(s) in RCA: 169] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/28/2020] [Indexed: 12/14/2022] Open
Abstract
Lactobacilli comprise an important group of probiotics for both human and animals. The emerging concern regarding safety problems associated with live microbial cells is enhancing the interest in using cell components and metabolites derived from probiotic strains. Here, we define cell structural components and metabolites of probiotic bacteria as paraprobiotics and postbiotics, respectively. Paraprobiotics and postbiotics produced from Lactobacilli consist of a wide range of molecules including peptidoglycans, surface proteins, cell wall polysaccharides, secreted proteins, bacteriocins, and organic acids, which mediate positive effect on the host, such as immunomodulatory, anti-tumor, antimicrobial, and barrier-preservation effects. In this review, we systematically summarize the paraprobiotics and postbiotics derived from Lactobacilli and their beneficial functions. We also discuss the mechanisms underlying their beneficial effects on the host, and their interaction with the host cells. This review may boost our understanding on the benefits and molecular mechanisms associated with paraprobiotics and probiotics from Lactobacilli, which may promote their applications in humans and animals.
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Affiliation(s)
- Tsegay Teame
- China-Norway Joint Lab on Fish Gastrointestinal Microbiota, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.,Tigray Agricultural Research Institute, Mekelle, Ethiopia
| | - Anran Wang
- AgricultureIsLife/EnvironmentIsLife and Precision Livestock and Nutrition Unit, AgroBioChem/TERRA, Gembloux Agro-Bio Tech, University of Liege, Passage des Deportes, Gembloux, Belgium
| | - Mingxu Xie
- Norway-China Fish Gastrointestinal Microbiota Joint Lab, Institute of Biology, Norwegian University of Science and Technology, Trondheim, Norway
| | - Zhen Zhang
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yalin Yang
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Qianwen Ding
- Norway-China Fish Gastrointestinal Microbiota Joint Lab, Institute of Biology, Norwegian University of Science and Technology, Trondheim, Norway
| | - Chenchen Gao
- China-Norway Joint Lab on Fish Gastrointestinal Microbiota, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Rolf Erik Olsen
- Norway-China Fish Gastrointestinal Microbiota Joint Lab, Institute of Biology, Norwegian University of Science and Technology, Trondheim, Norway
| | - Chao Ran
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Zhigang Zhou
- China-Norway Joint Lab on Fish Gastrointestinal Microbiota, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
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22
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Sharifi-Rad J, Rodrigues CF, Stojanović-Radić Z, Dimitrijević M, Aleksić A, Neffe-Skocińska K, Zielińska D, Kołożyn-Krajewska D, Salehi B, Milton Prabu S, Schutz F, Docea AO, Martins N, Calina D. Probiotics: Versatile Bioactive Components in Promoting Human Health. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E433. [PMID: 32867260 PMCID: PMC7560221 DOI: 10.3390/medicina56090433] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 08/19/2020] [Accepted: 08/25/2020] [Indexed: 02/08/2023]
Abstract
The positive impact of probiotic strains on human health has become more evident than ever before. Often delivered through food, dietary products, supplements, and drugs, different legislations for safety and efficacy issues have been prepared. Furthermore, regulatory agencies have addressed various approaches toward these products, whether they authorize claims mentioning a disease's diagnosis, prevention, or treatment. Due to the diversity of bacteria and yeast strains, strict approaches have been designed to assess for side effects and post-market surveillance. One of the most essential delivery systems of probiotics is within food, due to the great beneficial health effects of this system compared to pharmaceutical products and also due to the increasing importance of food and nutrition. Modern lifestyle or various diseases lead to an imbalance of the intestinal flora. Nonetheless, as the amount of probiotic use needs accurate calculations, different factors should also be taken into consideration. One of the novelties of this review is the presentation of the beneficial effects of the administration of probiotics as a potential adjuvant therapy in COVID-19. Thus, this paper provides an integrative overview of different aspects of probiotics, from human health care applications to safety, quality, and control.
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Affiliation(s)
- Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1991953381, Iran;
| | - Célia F. Rodrigues
- LEPABE—Department of Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal;
| | - Zorica Stojanović-Radić
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, 18000 Niš, Serbia; (Z.S.-R.); (M.D.); (A.A.)
| | - Marina Dimitrijević
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, 18000 Niš, Serbia; (Z.S.-R.); (M.D.); (A.A.)
| | - Ana Aleksić
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, 18000 Niš, Serbia; (Z.S.-R.); (M.D.); (A.A.)
| | - Katarzyna Neffe-Skocińska
- Department of Food Gastronomy and Food Hygiene, Warsaw University of Life Sciences (WULS), 02-776 Warszawa, Poland; (K.N.-S.); (D.Z.); (D.K.-K.)
| | - Dorota Zielińska
- Department of Food Gastronomy and Food Hygiene, Warsaw University of Life Sciences (WULS), 02-776 Warszawa, Poland; (K.N.-S.); (D.Z.); (D.K.-K.)
| | - Danuta Kołożyn-Krajewska
- Department of Food Gastronomy and Food Hygiene, Warsaw University of Life Sciences (WULS), 02-776 Warszawa, Poland; (K.N.-S.); (D.Z.); (D.K.-K.)
| | - Bahare Salehi
- Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam 44340847, Iran
- Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran
| | - Selvaraj Milton Prabu
- Department of Zoology, Annamalai University, Annamalai Nagar 608002, Chidambaram, India;
| | - Francine Schutz
- Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Natália Martins
- Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;
- Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, 4200-135 Porto, Portugal
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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23
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Babadi M, Khorshidi A, Aghadavood E, Samimi M, Kavossian E, Bahmani F, Mafi A, Shafabakhsh R, Satari M, Asemi Z. The Effects of Probiotic Supplementation on Genetic and Metabolic Profiles in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial. Probiotics Antimicrob Proteins 2020; 11:1227-1235. [PMID: 30535534 DOI: 10.1007/s12602-018-9490-z] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
This study was carried out to evaluate the effects of probiotic supplementation on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM) who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 patients with GDM. Participants were randomly divided into two groups to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum (2 × 109 CFU/g each) (n = 24) or placebo (n = 24) for 6 weeks. Probiotic intake upregulated peroxisome proliferator-activated receptor gamma (P = 0.01), transforming growth factor beta (P = 0.002) and vascular endothelial growth factor (P = 0.006), and downregulated gene expression of tumor necrosis factor alpha (P = 0.03) in peripheral blood mononuclear cells of subjects with GDM. In addition, probiotic supplementation significantly decreased fasting plasma glucose (β, - 3.43 mg/dL; 95% CI, - 6.48, - 0.38; P = 0.02), serum insulin levels (β, - 2.29 μIU/mL; 95% CI, - 3.60, - 0.99; P = 0.001), and insulin resistance (β, - 0.67; 95% CI, - 1.05, - 0.29; P = 0.001) and significantly increased insulin sensitivity (β, 0.009; 95% CI, 0.004, 0.01; P = 0.001) compared with the placebo. Additionally, consuming probiotic significantly decreased triglycerides (P = 0.02), VLDL-cholesterol (P = 0.02), and total-/HDL-cholesterol ratio (P = 0.006) and significantly increased HDL-cholesterol levels (P = 0.03) compared with the placebo. Finally, probiotic administration led to a significant reduction in plasma malondialdehyde (P < 0.001), and a significant elevation in plasma nitric oxide (P = 0.01) and total antioxidant capacity (P = 0.01) was observed compared with the placebo. Overall, probiotic supplementation for 6 weeks to patients with GDM had beneficial effects on gene expression related to insulin and inflammation, glycemic control, few lipid profiles, inflammatory markers, and oxidative stress.
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Affiliation(s)
- Mahtab Babadi
- Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Ahmad Khorshidi
- Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
| | - Esmat Aghadavood
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R., Iran
| | - Mansooreh Samimi
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Elham Kavossian
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Fereshteh Bahmani
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R., Iran
| | - Alireza Mafi
- Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Rana Shafabakhsh
- Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mahbobeh Satari
- Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R., Iran.
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24
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Stedman A, van Vliet AHM, A Chambers M, Gutierrez-Merino J. Gut commensal bacteria show beneficial properties as wildlife probiotics. Ann N Y Acad Sci 2020; 1467:112-132. [PMID: 32026493 DOI: 10.1111/nyas.14302] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 12/19/2019] [Accepted: 01/02/2020] [Indexed: 01/04/2023]
Abstract
Probiotics are noninvasive, environmentally friendly alternatives for reducing infectious diseases in wildlife species. Our aim in the present study was to evaluate the potential of gut commensals such as lactic acid bacteria (LAB) as wildlife probiotics. The LAB selected for our analyses were isolated from European badgers (Meles meles), a wildlife reservoir of bovine tuberculosis, and comprised four different genera: Enterococcus, Weissella, Pediococcus, and Lactobacillus. The enterococci displayed a phenotype and genotype that included the production of antibacterial peptides and stimulation of antiviral responses, as well as the presence of virulence and antibiotic resistance genes; Weissella showed antimycobacterial activity owing to their ability to produce lactate and ethanol; and lactobacilli and pediococci modulated proinflammatory phagocytic responses that associate with protection against pathogens, responses that coincide with the presence of immunomodulatory markers in their genomes. Although both lactobacilli and pediococci showed resistance to antibiotics, this was naturally acquired, and almost all isolates demonstrated a phylogenetic relationship with isolates from food and healthy animals. Our results show that LAB display probiotic benefits that depend on the genus, and that lactobacilli and pediococci are probably the most obvious candidates as probiotics against infectious diseases in wildlife because of their food-grade status and ability to modulate protective innate immune responses.
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Affiliation(s)
- Anna Stedman
- School of Biosciences and Medicine, University of Surrey-Nutritional Sciences, Guildford, United Kingdom.,The Pirbright Institute, Surrey, United Kingdom
| | | | - Mark A Chambers
- School of Veterinary Medicine, University of Surrey, Guildford, United Kingdom.,Bacteriology Department, Animal and Plant Health Agency, Addlestone, United Kingdom
| | - Jorge Gutierrez-Merino
- School of Biosciences and Medicine, University of Surrey-Nutritional Sciences, Guildford, United Kingdom
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25
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Yoo JH, Donowitz M. Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases. World J Gastroenterol 2019; 25:4125-4147. [PMID: 31435168 PMCID: PMC6700704 DOI: 10.3748/wjg.v25.i30.4125] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 06/14/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
The introduction of biologics such as anti-tumor necrosis factor (TNF) monoclonal antibodies followed by anti-integrins has dramatically changed the therapeutic paradigm of inflammatory bowel diseases (IBD). Furthermore, a newly developed anti-p40 subunit of interleukin (IL)-12 and IL-23 (ustekinumab) has been recently approved in the United States for patients with moderate to severe Crohn’s disease who have failed treatment with anti-TNFs. However, these immunosuppressive therapeutics which focus on anti-inflammatory mechanisms or immune cells still fail to achieve long-term remission in a significant percentage of patients. This strongly underlines the need to identify novel treatment targets beyond immune suppression to treat IBD. Recent studies have revealed the critical role of intestinal epithelial cells (IECs) in the pathogenesis of IBD. Physical, biochemical and immunologic driven barrier dysfunctions of epithelial cells contribute to the development of IBD. In addition, the recent establishment of adult stem cell-derived intestinal enteroid/organoid culture technology has allowed an exciting opportunity to study human IECs comprising all normal epithelial cells. This long-term epithelial culture model can be generated from endoscopic biopsies or surgical resections and recapitulates the tissue of origin, representing a promising platform for novel drug discovery in IBD. This review describes the advantages of intestinal enteroids/organoids as a research tool for intestinal diseases, introduces studies with these models in IBD, and gives a description of the current status of therapeutic approaches in IBD. Finally, we provide an overview of the current endeavors to identify a novel drug target for IBD therapy based on studies with human enteroids/organoids and describe the challenges in using enteroids/organoids as an IBD model.
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Affiliation(s)
- Jun-Hwan Yoo
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam 13496, South Korea
| | - Mark Donowitz
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
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26
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Bravo M, Combes T, Martinez FO, Cerrato R, Rey J, Garcia-Jimenez W, Fernandez-Llario P, Risco D, Gutierrez-Merino J. Lactobacilli Isolated From Wild Boar ( Sus scrofa) Antagonize Mycobacterium bovis Bacille Calmette-Guerin (BCG) in a Species-Dependent Manner. Front Microbiol 2019; 10:1663. [PMID: 31417502 PMCID: PMC6683848 DOI: 10.3389/fmicb.2019.01663] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 07/04/2019] [Indexed: 01/06/2023] Open
Abstract
Background: Wildlife poses a significant burden for the complete eradication of bovine tuberculosis (bTB). In particular, wild boar (Sus scrofa) is one of the most important reservoirs of Mycobacterium bovis, the causal agent of bTB. Wild boar can display from mild TB lesions, usually found in head lymph nodes, to generalized TB lesions distributed in different anatomical regions; but rarely clinical signs, which complicates the diagnosis of Mycobacterium bovis infection and bTB control. Among the possibilities for this variability in lesion distribution is the influence of the host-beneficial commensal-primed immune barrier. In this respect, beneficial microbes may delay bTB dissemination as a consequence of an antagonistic competition for nutrients and phagocytes. In order to explore this possibility, we have tested whether typical commensals such as lactobacilli have the capacity to reduce the survival rate of the surrogate M. bovis strain Bacillus Calmette-Guerin (BCG); and to modulate its phagocyte intake. Results: Three Lactobacillus species, L. casei, L. plantarum, and L. salivarius, isolated from wild boar feces displayed a pH-dependent inhibitory activity against BCG and influenced its intake by porcine blood phagocytes in a species-dependent manner. All lactobacilli showed a very significant bactericidal effect against BCG at low pH, but only isolates of L. plantarum and L. casei displayed such antimycobacterial activity at neutral pH. The genomes of these isolates revealed the presence of two-peptide bacteriocins whose precursor genes up-regulate in the presence of BCG cells. Furthermore, L. plantarum reduced significantly the BCG phagocytic intake, whereas L. casei had the opposite effect. L. salivarius had no significant influence on the phagocytic response to BCG. Conclusions: Our in vitro results show that lactobacilli isolated from wild boar antagonize BCG as a consequence of their antimycobacterial activity and a competitive phagocytic response. These findings suggest that commensal bacteria could play a beneficial role in influencing the outcome of bTB dissemination. Further work with lactobacilli as a potential competitive pressure to control bTB will need to take into account the complex nature of the commensal microbiome, the specific immunity of the wild boar and the in vivo infection context with pathogenic strains of M. bovis.
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Affiliation(s)
- Maria Bravo
- Innovación en Gestión y Conservación de Ungulados SL, Cáceres, Spain.,Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain
| | - Theo Combes
- Department of Biochemical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom
| | - Fernando O Martinez
- Department of Biochemical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom
| | - Rosario Cerrato
- Innovación en Gestión y Conservación de Ungulados SL, Cáceres, Spain
| | - Joaquín Rey
- Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain
| | | | | | - David Risco
- Innovación en Gestión y Conservación de Ungulados SL, Cáceres, Spain
| | - Jorge Gutierrez-Merino
- Department of Nutritional Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom
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27
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Li C, Bei T, Niu Z, Guo X, Wang M, Lu H, Gu X, Tian H. Adhesion and Colonization of the Probiotic Lactobacillus rhamnosus Labeled by Dsred2 in Mouse Gut. Curr Microbiol 2019; 76:896-903. [PMID: 31115599 DOI: 10.1007/s00284-019-01706-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 05/09/2019] [Indexed: 12/15/2022]
Abstract
The health-promoting effects of the probiotic strain Lactobacillus rhamnosus are based on its adherence and colonization ability. However, little is known about its adhesion and colonization rates. Lactobacillus rhamnosus in mouse intestinal mucosa a mutant of the red fluorescence protein (RFP) DSred2 was used to tag L. rhamnosus to observe the adhesion and distribution of L. rhamnosus in mouse intestinal mucosa. A mutant of the red fluorescence protein (RFP) Dsred2 was used to tag L. rhamnosus to allow us to observe and distinguish it in the mouse intestine. Seven-week-old female BALB/c mice were fed once (at day 0) with an oral administration of the labeled L. rhamnosus, and the number of labeled bacteria was detected in different regions of the intestinal tract at 3 h and at day 1, 2, 3, 4, 5, 6, 7, and 15 after administration. The labeling process changed the morphology of L. rhamnosus, as it appeared after observation under the microscope, but did not change its basic probiotic properties in vitro. In vivo, labeled L. rhamnosus reached the colonization peak at the fourth day after gavage. From the distribution point of view, the number of colonization strains increased from the proximal to the distal small intestine (duodenum < jejunum < ileum) and the number of strains in the colon was less than the distal small intestine (ileum). The labeling protocol actually allowed the detection of the distribution and adhesion of this bacterium to the intestine, thus demonstrating that the health-promoting effects of this probiotic are satisfied. This study provides a scientific basis in the use of probiotics such as L. rhamnosus in functional foods.
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Affiliation(s)
- Chen Li
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China
| | - Tingting Bei
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China
| | - Zhihua Niu
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China
| | - Xin Guo
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China
| | - Miaoshu Wang
- New Hope Tensun (Hebei) Dairy Co., Ltd, Baoding, China
| | - Haiqiang Lu
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China
| | - Xinxi Gu
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China
| | - Hongtao Tian
- College of Food Science and Technology, Agricultural University of Hebei, Baoding, 071000, China.
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28
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Etienne-Mesmin L, Chassaing B, Desvaux M, De Paepe K, Gresse R, Sauvaitre T, Forano E, de Wiele TV, Schüller S, Juge N, Blanquet-Diot S. Experimental models to study intestinal microbes–mucus interactions in health and disease. FEMS Microbiol Rev 2019; 43:457-489. [DOI: 10.1093/femsre/fuz013] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 05/31/2019] [Indexed: 02/06/2023] Open
Abstract
ABSTRACT
A close symbiotic relationship exists between the intestinal microbiota and its host. A critical component of gut homeostasis is the presence of a mucus layer covering the gastrointestinal tract. Mucus is a viscoelastic gel at the interface between the luminal content and the host tissue that provides a habitat to the gut microbiota and protects the intestinal epithelium. The review starts by setting up the biological context underpinning the need for experimental models to study gut bacteria-mucus interactions in the digestive environment. We provide an overview of the structure and function of intestinal mucus and mucins, their interactions with intestinal bacteria (including commensal, probiotics and pathogenic microorganisms) and their role in modulating health and disease states. We then describe the characteristics and potentials of experimental models currently available to study the mechanisms underpinning the interaction of mucus with gut microbes, including in vitro, ex vivo and in vivo models. We then discuss the limitations and challenges facing this field of research.
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Affiliation(s)
- Lucie Etienne-Mesmin
- Université Clermont Auvergne, INRA, MEDIS, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France
| | - Benoit Chassaing
- Neuroscience Institute, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303 , USA
- Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave, Atlanta, GA 30303 , USA
| | - Mickaël Desvaux
- Université Clermont Auvergne, INRA, MEDIS, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France
| | - Kim De Paepe
- Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| | - Raphaële Gresse
- Université Clermont Auvergne, INRA, MEDIS, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France
| | - Thomas Sauvaitre
- Université Clermont Auvergne, INRA, MEDIS, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France
| | - Evelyne Forano
- Université Clermont Auvergne, INRA, MEDIS, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France
| | - Tom Van de Wiele
- Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| | - Stephanie Schüller
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom
- Quadram Institute Bioscience, Norwich Research Park, Norwich NR7UQ, United Kingdom
| | - Nathalie Juge
- Quadram Institute Bioscience, Norwich Research Park, Norwich NR7UQ, United Kingdom
| | - Stéphanie Blanquet-Diot
- Université Clermont Auvergne, INRA, MEDIS, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France
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29
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Murphy R, Morgan X, Wang X, Wickens K, Purdie G, Fitzharris P, Otal A, Lawley B, Stanley T, Barthow C, Crane J, Mitchell E, Tannock G. Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: sub-sample analysis from a RCT. Benef Microbes 2019; 10:5-17. [DOI: 10.3920/bm2017.0191] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.
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Affiliation(s)
- R. Murphy
- Faculty of Medical and Health Sciences, University of Auckland, Park Road, Grafton, 1142 Auckland, New Zealand
| | - X.C. Morgan
- Department of Microbiology and Immunology, University of Otago, 720 Cumberland St, Dunedin 9016 New Zealand
| | - X.Y. Wang
- Department of Microbiology and Immunology, University of Otago, 720 Cumberland St, Dunedin 9016 New Zealand
| | - K. Wickens
- Department of Medicine, University of Otago, P.O. Box 7343, Wellington South, 6021 Wellington, New Zealand
| | - G. Purdie
- Department of Medicine, University of Otago, P.O. Box 7343, Wellington South, 6021 Wellington, New Zealand
| | - P. Fitzharris
- Department of Immunology, Auckland City Hospital, 2 Park Road, Grafton, 1023 Auckland, New Zealand
| | - A. Otal
- Department of Microbiology and Immunology, University of Otago, 720 Cumberland St, Dunedin 9016 New Zealand
| | - B. Lawley
- Department of Microbiology and Immunology, University of Otago, 720 Cumberland St, Dunedin 9016 New Zealand
| | - T. Stanley
- Department of Medicine, University of Otago, P.O. Box 7343, Wellington South, 6021 Wellington, New Zealand
| | - C. Barthow
- Department of Medicine, University of Otago, P.O. Box 7343, Wellington South, 6021 Wellington, New Zealand
| | - J. Crane
- Department of Medicine, University of Otago, P.O. Box 7343, Wellington South, 6021 Wellington, New Zealand
| | - E.A. Mitchell
- Department of Paediatrics, University of Auckland, Auckland 1142, New Zealand
| | - G.W. Tannock
- Microbiome Otago, University of Otago, 720 Cumberland St., 9016 Dunedin, New Zealand
- Department of Microbiology and Immunology, University of Otago, 720 Cumberland St, Dunedin 9016 New Zealand
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30
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Kleerebezem M, Binda S, Bron PA, Gross G, Hill C, van Hylckama Vlieg JE, Lebeer S, Satokari R, Ouwehand AC. Understanding mode of action can drive the translational pipeline towards more reliable health benefits for probiotics. Curr Opin Biotechnol 2018; 56:55-60. [PMID: 30296737 DOI: 10.1016/j.copbio.2018.09.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 08/28/2018] [Accepted: 09/07/2018] [Indexed: 12/18/2022]
Abstract
The different levels of knowledge described in a translational pipeline (the connection of molecular mechanisms with pre-clinical physiological and human health effects) are not complete for many probiotics. At present, we are not in a position to fully understand the mechanistic basis of many well established probiotic health benefits which, in turn, limits our ability to use mechanisms to predict which probiotics are likely to be effective in any given population. Here we suggest that this concept of a translation pipeline connecting mechanistic insights to probiotic efficacy can support the selection and production of improved probiotic products. Such a conceptual pipeline would also provide a framework for the design of clinical trials to convincingly demonstrate the benefit of probiotics to human health in well-defined subpopulations.
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Affiliation(s)
- Michiel Kleerebezem
- Host Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands.
| | - Sylvie Binda
- Danone Nutricia Research, Centre Daniel Carasso, Palaiseau, France
| | | | - Gabriele Gross
- Innovative Health Sciences, Reckitt Benckiser, Nijmegen, The Netherlands
| | - Colin Hill
- School of Microbiology and APC Microbiome Ireland, University College Cork, Cork, Ireland
| | | | - Sarah Lebeer
- Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
| | - Reetta Satokari
- Immunobiology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Arthur C Ouwehand
- Global Health and Nutrition Sciences, DuPont Nutrition and Health, Kantvik, Finland
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31
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Martens K, Pugin B, De Boeck I, Spacova I, Steelant B, Seys SF, Lebeer S, Hellings PW. Probiotics for the airways: Potential to improve epithelial and immune homeostasis. Allergy 2018; 73:1954-1963. [PMID: 29869783 DOI: 10.1111/all.13495] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/29/2018] [Indexed: 12/30/2022]
Abstract
Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefit on the host. The therapeutic effects of probiotics have been mostly studied in the gastrointestinal tract, but recent evidence points toward the potential of these bacteria to prevent and/or treat chronic airway diseases. In this review, possible mechanisms of action of probiotics in the airways are described, with a particular focus on their capacity to modulate the epithelial barrier function and their mode of interaction with the immune system. Indeed, probiotic bacteria, mostly lactobacilli, can promote the expression and regulation of tight junctions and adherence junctions, resulting in the restoration of a defective epithelial barrier. These bacteria interact with the epithelial barrier and immune cells through pattern recognition receptors, such as Toll-like receptors, which upon activation can stimulate or suppress various immune responses. Finally, the clinical potential of probiotics to treat inflammatory diseases of the upper and lower respiratory tract, and the difference between their mode of application (eg, oral or nasal) are discussed here.
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Affiliation(s)
- K. Martens
- Clinical Immunology Department of Microbiology and Immunology KU Leuven Leuven Belgium
| | - B. Pugin
- Clinical Immunology Department of Microbiology and Immunology KU Leuven Leuven Belgium
| | - I. De Boeck
- Department of Bioscience Engineering University of Antwerp Antwerp Belgium
| | - I. Spacova
- Department of Bioscience Engineering University of Antwerp Antwerp Belgium
| | - B. Steelant
- Clinical Immunology Department of Microbiology and Immunology KU Leuven Leuven Belgium
| | - S. F. Seys
- Clinical Immunology Department of Microbiology and Immunology KU Leuven Leuven Belgium
| | - S. Lebeer
- Department of Bioscience Engineering University of Antwerp Antwerp Belgium
| | - P. W. Hellings
- Clinical Immunology Department of Microbiology and Immunology KU Leuven Leuven Belgium
- Clinical Division of Otorhinolaryngology, Head and Neck Surgery University Hospitals Leuven Leuven Belgium
- Department of Otorhinolaryngology University Hospitals Ghent Ghent Belgium
- Department of Otorhinolaryngology Academic Medical Center University of Amsterdam Amsterdam the Netherlands
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32
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Lebeer S, Bron PA, Marco ML, Van Pijkeren JP, O'Connell Motherway M, Hill C, Pot B, Roos S, Klaenhammer T. Identification of probiotic effector molecules: present state and future perspectives. Curr Opin Biotechnol 2017; 49:217-223. [PMID: 29153882 DOI: 10.1016/j.copbio.2017.10.007] [Citation(s) in RCA: 174] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 10/24/2017] [Accepted: 10/31/2017] [Indexed: 01/01/2023]
Abstract
Comprehension of underlying mechanisms of probiotic action will support rationale selection of probiotic strains and targeted clinical study design with a higher likelihood of success. This will consequently contribute to better substantiation of health claims. Here, we aim to provide a perspective from a microbiology point of view that such comprehensive understanding is not straightforward. We show examples of well-documented probiotic effector molecules in Lactobacillus and Bifidobacterium strains, including surface-located molecules such as specific pili, S-layer proteins, exopolysaccharides, muropeptides, as well as more widely produced metabolites such as tryptophan-related and histamine-related metabolites, CpG-rich DNA, and various enzymes such as lactase and bile salt hydrolases. We also present recent advances in genetic tool development, microbiome analyses and model systems, as well as perspectives on how the field could further progress. This opinion is based on a discussion group organized at the annual meeting of the International Scientific Association on Probiotics and Prebiotics (ISAPP) in June 2017.
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Affiliation(s)
- Sarah Lebeer
- University of Antwerp, Department of Bioscience Engineering, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
| | | | - Maria L Marco
- Department of Food Science & Technology, University of California, Davis, USA
| | | | - Mary O'Connell Motherway
- School of Microbiology and APC Microbiome Institute, National University of Ireland, Western Road, Cork, Ireland
| | - Colin Hill
- School of Microbiology and APC Microbiome Institute, National University of Ireland, Western Road, Cork, Ireland
| | - Bruno Pot
- Yakult R&D, Europe, Almere, The Netherlands; Vrije Universiteit Brussels, Belgium
| | - Stefan Roos
- Swedish University of Agricultural Sciences & BioGaia AB, Sweden
| | - Todd Klaenhammer
- Department of Food, Bioprocessing & Nutrition Sciences, North Carolina State University, Raleigh, USA
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Tamtaji OR, Kouchaki E, Salami M, Aghadavod E, Akbari E, Tajabadi-Ebrahimi M, Asemi Z. The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin, and Lipids in Patients With Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial. J Am Coll Nutr 2017; 36:660-665. [PMID: 28922099 DOI: 10.1080/07315724.2017.1347074] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Limited data are available assessing the effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis (MS). OBJECTIVES The current study was conducted to assess the effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with MS. METHODS This randomized, double-blind, placebo-controlled clinical trial was performed among 40 patients with MS. Participants were randomly assigned into two groups to receive either a probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony-forming units/g each; n = 20) or placebo (n = 20) for 12 weeks. Gene expression related to inflammation, insulin, and lipids was quantified in blood samples of patients with MS with the reverse transcription polymerase chain reaction (RT-PCR) method. RESULTS We found that compared with placebo, probiotic supplementation down-regulated gene expression of interleukin-8 (IL-8; p < 0.001) and tumor necrosis factor-alpha (TNF-α) mRNA (p < .001) in peripheral blood mononuclear cells of patients with MS. We did not observe any significant effect of probiotic supplementation on gene expression of interleukin-1 (IL-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), or oxidized low-density lipoprotein receptor (LDLR) in peripheral blood mononuclear cells of patients with MS. CONCLUSIONS Overall, probiotic supplementation for 12 weeks in patients with MS significantly improved gene expression of IL-8 and TNF-α but did not influence IL-1, PPAR-γ, or LDLR.
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Affiliation(s)
- Omid Reza Tamtaji
- a Physiology Research Center , Kashan University of Medical Sciences , Kashan , Iran
| | - Ebrahim Kouchaki
- a Physiology Research Center , Kashan University of Medical Sciences , Kashan , Iran
- b Department of Neurology, School of Medicine , Kashan University of Medical Sciences , Kashan , Iran
| | - Mahmoud Salami
- a Physiology Research Center , Kashan University of Medical Sciences , Kashan , Iran
| | - Esmat Aghadavod
- a Physiology Research Center , Kashan University of Medical Sciences , Kashan , Iran
| | - Elmira Akbari
- c Research Center for Biochemistry and Nutrition in Metabolic Diseases , Kashan University of Medical Sciences , Kashan , Iran
| | | | - Zatollah Asemi
- c Research Center for Biochemistry and Nutrition in Metabolic Diseases , Kashan University of Medical Sciences , Kashan , Iran
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Younes JA, Lievens E, Hummelen R, van der Westen R, Reid G, Petrova MI. Women and Their Microbes: The Unexpected Friendship. Trends Microbiol 2017; 26:16-32. [PMID: 28844447 DOI: 10.1016/j.tim.2017.07.008] [Citation(s) in RCA: 151] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 07/17/2017] [Accepted: 07/31/2017] [Indexed: 12/14/2022]
Abstract
Communities of microbiota have been associated with numerous health outcomes, and while much emphasis has been placed on the gastrointestinal niche, there is growing interest in the microbiome specific for female reproductive health and the health of their offspring. The vaginal microbiome plays an essential role not only in health and dysbiosis, but also potentially in successful fertilization and healthy pregnancies. In addition, microbial communities have been isolated from formerly forbidden sterile niches such as the placenta, breast, uterus, and Fallopian tubes, strongly suggesting an additional microbial role in women's health. A combination of maternally linked prenatal, birth, and postnatal factors, together with environmental and medical interventions, influence early and later life through the microbiome. Here, we review the role of microbes in female health focusing on the vaginal tract and discuss how male and female reproductive microbiomes are intertwined with conception and how mother-child microbial transfer is a key determinant in infant health, and thus the next generation.
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Affiliation(s)
- Jessica A Younes
- Winclove Probiotics, 11 Hulstweg, 1032 LB Amsterdam, The Netherlands.
| | - Elke Lievens
- KU Leuven, Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, 3001 Leuven, Belgium; University of Antwerp, Department of Bioscience Engineering, Antwerp, Belgium
| | - Ruben Hummelen
- McMaster University, Department of Family Medicine, 100 Main Street West Hamilton, ON L8P 1H6, Canada
| | - Rebecca van der Westen
- University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands
| | - Gregor Reid
- Human Microbiology and Probiotics, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada; Departments of Microbiology & Immunology, and Surgery, The University of Western Ontario, London, Ontario, N6A 5C1, Canada
| | - Mariya I Petrova
- KU Leuven, Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, 3001 Leuven, Belgium; University of Antwerp, Department of Bioscience Engineering, Antwerp, Belgium.
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Yu J, Zhu YH, Yang GY, Zhang W, Zhou D, Su JH, Wang JF. Anti-inflammatory capacity of Lactobacillus rhamnosus GG in monophasic variant Salmonella infected piglets is correlated with impeding NLRP6-mediated host inflammatory responses. Vet Microbiol 2017; 210:91-100. [PMID: 29103703 DOI: 10.1016/j.vetmic.2017.08.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 08/08/2017] [Accepted: 08/15/2017] [Indexed: 01/10/2023]
Abstract
In this study, we investigated the effect of Lactobacillus rhamnosus GG strain (LGG) in ameliorating enteritis in newly weaned pigs following challenge with a monophasic variant of Salmonella enterica serovar Typhimurium (serotyped as 4,[5],12:i:-), which has been linked to disease in humans and livestocks over the past 10 years. In weaned pigs, S. enterica serovar 4,[5],12:i:- induced the mRNA expression of toll like receptor (TLR) 5 and TLR4, while increasing interleukin (IL)-8 and IL-6 mRNA expression in the jejunum. The monophasic variant Salmonella stimulated the expression of nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) mRNA in the ileum, which was accompanied by phosphorylation of IκB-α, an inhibitor of NF-κB, activating the NF-κB pathway and promoting the release of inflammatory cytokines. Oral administration of LGG attenuated the Salmonella-induced increases in the expression of NOD1 mRNA of jejunal and ileal tissues. LGG promoted the secretion of immunoglobulin A in different intestinal segments but did not induce expression of polymeric immunoglobulin receptor. LGG also impeded the activation of the Nod-like receptor protein (NLRP) 6/apoptosis-associated speck-like protein/caspase-1 inflammasome and decreased the production of IL-18 in the ileum during Salmonella infection. In contrast, activation of the NLRP3 inflammasome was not altered. Our data indicate that LGG accelerated the clearance of Salmonella in the early phase of infection and prevented the excessive inflammatory responses in S. enterica serovar 4,[5],12:i:- model. LGG ameliorates inflammation induced by infection with the monophasic variant Salmonella via inhibition of the canonical NF-κB pathway and attenuation of the NLRP6-mediated inflammasome in the intestine.
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Affiliation(s)
- Jiao Yu
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Yao-Hong Zhu
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Gui-Yan Yang
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Wei Zhang
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Dong Zhou
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Jin-Hui Su
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Jiu-Feng Wang
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
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von Ossowski I. Novel Molecular Insights about Lactobacillar Sortase-Dependent Piliation. Int J Mol Sci 2017; 18:ijms18071551. [PMID: 28718795 PMCID: PMC5536039 DOI: 10.3390/ijms18071551] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 07/11/2017] [Accepted: 07/14/2017] [Indexed: 01/09/2023] Open
Abstract
One of the more conspicuous structural features that punctuate the outer cell surface of certain bacterial Gram-positive genera and species is the sortase-dependent pilus. As these adhesive and variable-length protrusions jut outward from the cell, they provide a physically expedient and useful means for the initial contact between a bacterium and its ecological milieu. The sortase-dependent pilus displays an elongated macromolecular architecture consisting of two to three types of monomeric protein subunits (pilins), each with their own specific function and location, and that are joined together covalently by the transpeptidyl activity of a pilus-specific C-type sortase enzyme. Sortase-dependent pili were first detected among the Gram-positive pathogens and subsequently categorized as an essential virulence factor for host colonization and tissue invasion by these harmful bacteria. However, the sortase-dependent pilus was rebranded as also a niche-adaptation factor after it was revealed that “friendly” Gram-positive commensals exhibit the same kind of pilus structures, which includes two contrasting gut-adapted species from the Lactobacillus genus, allochthonous Lactobacillus rhamnosus and autochthonous Lactobacillus ruminis. This review will highlight and discuss what has been learned from the latest research carried out and published on these lactobacillar pilus types.
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Affiliation(s)
- Ingemar von Ossowski
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki FIN-00014, Finland.
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37
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Li X, Li X, Shang Q, Gao Z, Hao F, Guo H, Guo C. Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation. Free Radic Biol Med 2017; 108:32-43. [PMID: 28323128 DOI: 10.1016/j.freeradbiomed.2017.03.011] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 03/01/2017] [Accepted: 03/11/2017] [Indexed: 01/08/2023]
Abstract
Fecal microbiota transplantation (FMT) has been used successfully to treat a variety of gastroenterological diseases. The alterations of microbiota in mouse models of necrotizing enterocolitis (NEC) as well as in patients suggested the possibility of treating NEC with FMT. Here we show that FMT caused an improvement in the histopathology and symptoms of NEC in WT mice, but not Grx1-/- mice. FMT eliminated O2•- production and promoted NO production in experimental NEC mice though the modulation of S-glutathionylation of eNOS (eNOS-SSG). FMT decreased the extent of TLR4-mediated proinflammatory signaling though TLR9 in the intestinal mucosa tissue. FMT also suppressed intestinal apoptosis and bacterial translocation across the intestinal barrier, which was accompanied by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulated lymphocyte proportions. FMT is effective in a mouse model of NEC through the modulation of oxidative stress and reduced colon inflammation.
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Affiliation(s)
- Xiaomei Li
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaowen Li
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Qingjuan Shang
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Pathology, Linyi People's Hospital, Linyi, Shandong, China
| | - Zongwei Gao
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Pathology, Linyi People's Hospital, Linyi, Shandong, China
| | - Fabao Hao
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Hongjie Guo
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Chunbao Guo
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
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Mishra AK, Megta AK, Palva A, von Ossowski I, Krishnan V. Crystallization and X-ray diffraction analysis of SpaE, a basal pilus protein from the gut-adapted Lactobacillus rhamnosus GG. Acta Crystallogr F Struct Biol Commun 2017; 73:321-327. [PMID: 28580919 PMCID: PMC5458388 DOI: 10.1107/s2053230x17006963] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 05/09/2017] [Indexed: 12/19/2022] Open
Abstract
SpaE is the predicted basal pilin subunit in the sortase-dependent SpaFED pilus from the gut-adapted and commensal Lactobacillus rhamnosus GG. Thus far, structural characterization of the cell-wall-anchoring basal pilins has remained difficult and has been limited to only a few examples from pathogenic genera and species. To gain a further structural understanding of the molecular mechanisms that are involved in the anchoring and assembly of sortase-dependent pili in less harmful bacteria, L. rhamnosus GG SpaE for crystallization was produced by recombinant expression in Escherichia coli. Although several attempts to crystallize the SpaE protein were unsuccessful, trigonal crystals that diffracted to a resolution of 3.1 Å were eventually produced using PEG 3350 as a precipitant and high protein concentrations. Further optimization with a combination of additives led to the generation of SpaE crystals in an orthorhombic form that diffracted to a higher resolution of 1.5 Å. To expedite structure determination by SAD phasing, selenium-substituted (orthorhombic) SpaE crystals were grown and X-ray diffraction data were collected to 1.8 Å resolution.
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Affiliation(s)
- Arjun K. Mishra
- Laboratory of Structural Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad 121 001, India
| | - Abhin Kumar Megta
- Laboratory of Structural Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad 121 001, India
- School of Biotechnology, KIIT University, Odisha 751 024, India
| | - Airi Palva
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
| | | | - Vengadesan Krishnan
- Laboratory of Structural Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad 121 001, India
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Dissanayake E, Shimojo N. Probiotics and Prebiotics in the Prevention and Treatment of Atopic Dermatitis. PEDIATRIC ALLERGY, IMMUNOLOGY, AND PULMONOLOGY 2016; 29:174-180. [DOI: 10.1089/ped.2016.0708] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Eishika Dissanayake
- Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoki Shimojo
- Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan
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40
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Tian Z, Liu X, Dai R, Xiao Y, Wang X, Bi D, Shi D. Enterococcus faecium HDRsEf1 Protects the Intestinal Epithelium and Attenuates ETEC-Induced IL-8 Secretion in Enterocytes. Mediators Inflamm 2016; 2016:7474306. [PMID: 27890970 PMCID: PMC5116501 DOI: 10.1155/2016/7474306] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 08/21/2016] [Accepted: 09/28/2016] [Indexed: 12/25/2022] Open
Abstract
The probiotic Enterococcus faecium HDRsEf1 (Ef1) has been shown to have positive effects on piglet diarrhoea, but the mechanism has not yet been elucidated. In this study, using the IPEC-J2 cell line to mimic intestinal epithelial cells and enterotoxigenic Escherichia coli (ETEC) K88ac as a representative intestinal pathogen, the mechanism underlying Ef1 protection against an enteropathogen was investigated. The results demonstrated that Ef1 was effective in displacing K88ac from the IPEC-J2 cell layer. Moreover, Ef1 and its cell-free supernatant (S-Ef1) modulate IL-8 released by IPEC-J2 cells. Ef1 and its cell-free supernatant showed the potential to protect enterocytes from an acute inflammatory response. In addition, Ef1 and its cell-free supernatant increased the transepithelial electrical resistance (TEER) of the enterocyte monolayer, thus strengthening the intestinal barrier against ETEC. These results may contribute to the development of therapeutic interventions using Ef1 in intestinal disorders of piglets.
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Affiliation(s)
- Zhongyuan Tian
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Xiaofang Liu
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Ran Dai
- College of Animal Science and Technology, Agricultural University of Hebei, Baoding 071000, China
| | - Yuncai Xiao
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Xiliang Wang
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Dingren Bi
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Deshi Shi
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China
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Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice. Sci Rep 2016; 6:36083. [PMID: 27786292 PMCID: PMC5081535 DOI: 10.1038/srep36083] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 10/11/2016] [Indexed: 12/12/2022] Open
Abstract
The fibroblast cell line of 3T3-L1 was used as a cell model for screening and evaluating the feasibility of probiotic components in improving animal lipid metabolisms. The extracts from 12 Lactobacillus strains caused significantly reduced triacylglycerol (TAG) accumulation but with severe inflammation induction in 3T3-L1 adipocytes. Interestingly, exopolysaccharides (EPS) from LGG (Lactobacillus rhamnosus GG) significantly decreased the TAG accumulation without any inflammation. The anti-obesity effect of EPS was confirmed in high-fat-diets feeding mice. Fat pads of mice injected with EPS (50 mg/kg) every two days for two weeks were significantly reduced with much smaller adipocytes, compared with the counterparts. The levels of TAG and cholesterol ester in liver, as well as serum TAG, were decreased in EPS injected mice. In addition, down-regulated inflammation was observed in adipose tissue and liver. Interestingly, the expression of TLR2 in adipose tissue and 3T3-L1 cells was significantly increased by EPS addition. Moreover, the reverse of TAG accumulation in TLR2 knockdown 3T3-L1 in the presence of EPS confirmed that the inhibition effect of EPS on adipogenesis was mediated by TLR2. EPS from LGG has the potential for therapeutic development to intervene lipid metabolic disorders in mammals.
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Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases. Sci Rep 2016; 6:29946. [PMID: 27425195 PMCID: PMC4947902 DOI: 10.1038/srep29946] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 06/27/2016] [Indexed: 01/08/2023] Open
Abstract
Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes.
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Chaurasia P, Pratap S, von Ossowski I, Palva A, Krishnan V. New insights about pilus formation in gut-adapted Lactobacillus rhamnosus GG from the crystal structure of the SpaA backbone-pilin subunit. Sci Rep 2016; 6:28664. [PMID: 27349405 PMCID: PMC4923907 DOI: 10.1038/srep28664] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 06/08/2016] [Indexed: 12/11/2022] Open
Abstract
Thus far, all solved structures of pilin-proteins comprising sortase-assembled pili are from pathogenic genera and species. Here, we present the first crystal structure of a pilin subunit (SpaA) from a non-pathogen host (Lactobacillus rhamnosus GG). SpaA consists of two tandem CnaB-type domains, each with an isopeptide bond and E-box motif. Intriguingly, while the isopeptide bond in the N-terminal domain forms between lysine and asparagine, the one in the C-terminal domain atypically involves aspartate. We also solved crystal structures of mutant proteins where residues implicated in forming isopeptide bonds were replaced. Expectedly, the E-box-substituted E139A mutant lacks an isopeptide bond in the N-terminal domain. However, the C-terminal E269A substitution gave two structures; one of both domains with their isopeptide bonds present, and another of only the N-terminal domain, but with an unformed isopeptide bond and significant conformational changes. This latter crystal structure has never been observed for any other Gram-positive pilin. Notably, the C-terminal isopeptide bond still forms in D295N-substituted SpaA, irrespective of E269 being present or absent. Although E-box mutations affect SpaA proteolytic and thermal stability, a cumulative effect perturbing normal pilus polymerization was unobserved. A model showing the polymerized arrangement of SpaA within the SpaCBA pilus is proposed.
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Affiliation(s)
- Priyanka Chaurasia
- Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad-121 001, India.,Department of Biotechnology, Manipal University, Karnataka, 576104, India
| | - Shivendra Pratap
- Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad-121 001, India
| | | | - Airi Palva
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
| | - Vengadesan Krishnan
- Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad-121 001, India
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Abstract
Despite decades of research on necrotizing enterocolitis, we still do not fully understand the pathogenesis of the disease, how to prevent or how to treat the disease. However, as a result of recent significant advances in the microbiology, molecular biology, and cell biology of the intestine of premature infants and infants with necrotizing enterocolitis, there is some hope that research into this devastating disease will yield some important translation into improved outcomes.
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Affiliation(s)
- Simon Eaton
- UCL Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
| | - Clare M Rees
- UCL Institute of Child Health and Great Ormond Street Hospital for Children, London, UK
| | - Nigel J Hall
- Faculty of Medicine, University of Southampton, Southampton, UK
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Immunomodulation of Lactobacillus rhamnosus GG (LGG)-derived soluble factors on antigen-presenting cells of healthy blood donors. Sci Rep 2016; 6:22845. [PMID: 26961406 PMCID: PMC4785377 DOI: 10.1038/srep22845] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Accepted: 02/19/2016] [Indexed: 01/30/2023] Open
Abstract
Lactobacillus rhamnosus GG (LGG) cells have been shown to promote type-1 immune responsiveness; however knowledge of immunomodulation of soluble factors secreted by LGG is limited. This is the first study to investigate whether LGG soluble factors promote a comparable immune responsiveness as the bacterial cells. Both treatments − LGG conditioned medium with (CM + LGG) or without (CM) LGG cells, in this study increased expression of several toll-like receptors (TLRs) in all studied cell types and antigen presentation-associated receptor HLA-DR in macrophages and “intermediate” monocytes; but decreased that of activation markers on monocytes and macrophages and production of IL-10, IL-12 and TNFα in macrophages. In co-culture with mononuclear cells, CM increased Th1-type cytokine profile but not as pronounced as CM + LGG. This study suggests that LGG soluble factors exert similar immunomodulatory effects as the intact cells, but cells may be required for optimal type-1 immune responsiveness polarizing capacity of this probiotic strain.
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Smith-Norowitz TA, Chotikanatis K, Erstein DP, Perlman J, Norowitz YM, Joks R, Durkin HG, Hammerschlag MR, Kohlhoff S. Chlamydia pneumoniae enhances the Th2 profile of stimulated peripheral blood mononuclear cells from asthmatic patients. Hum Immunol 2016; 77:382-8. [PMID: 26924667 DOI: 10.1016/j.humimm.2016.02.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 02/23/2016] [Accepted: 02/24/2016] [Indexed: 01/31/2023]
Abstract
Chlamydia pneumoniae is a cause of respiratory infection in adults and children. There is evidence for an association between atypical bacterial respiratory pathogens and the pathogenesis of asthma. We compared T helper (Th) responses in C. pneumoniae - infected peripheral blood mononuclear cells (PBMC) in patients with or without asthma. PBMC (1×10(6)/mL) from asthmatic patients (N=11) and non-asthmatic controls (N=12) were infected or mock-infected for 1h +/- C. pneumoniae TW-183 at a multiplicity of infection (MOI)=1 and MOI=0.1, or cultured for 24h +/- Lactobacillus rhamnosus GG (LGG). Interleukin (IL)-4, IL-10, IL-12, Interferon (IFN)-gamma and total IgE levels were measured in supernatants (ELISA). C. pneumoniae infection led to an increase (>50%) of IgE levels in PBMC from asthmatics, compared with mock-infected on day 10; IgE wasn't detected in non-asthmatics. C. pneumoniae - infected PBMC from asthmatics increased levels of IL-4 and IFN-gamma after 24h, compared with PBMC alone; levels of IL-10 and IL-12 were low. When uninfected-PBMC from asthmatics were LGG-stimulated, after 24h, IL-4 was undetectable, but IL-10, IL-12, and IFN-gamma increased, compared with PBMC alone. Thus, C. pneumoniae infection has the ability to induce allergic responses in PBMC of asthmatics, as evidenced by production of Th2 responses and IgE.
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Affiliation(s)
- Tamar A Smith-Norowitz
- Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States; Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States.
| | - Kobkul Chotikanatis
- Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - David P Erstein
- Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Jason Perlman
- Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Yitzchok M Norowitz
- Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Rauno Joks
- Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States; Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Helen G Durkin
- Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States; Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Margaret R Hammerschlag
- Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Stephan Kohlhoff
- Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States; Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
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Mikelsaar M, Sepp E, Štšepetova J, Songisepp E, Mändar R. Biodiversity of Intestinal Lactic Acid Bacteria in the Healthy Population. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 932:1-64. [DOI: 10.1007/5584_2016_3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Yu X, Jaatinen A, Rintahaka J, Hynönen U, Lyytinen O, Kant R, Åvall-Jääskeläinen S, von Ossowski I, Palva A. Human Gut-Commensalic Lactobacillus ruminis ATCC 25644 Displays Sortase-Assembled Surface Piliation: Phenotypic Characterization of Its Fimbrial Operon through In Silico Predictive Analysis and Recombinant Expression in Lactococcus lactis. PLoS One 2015; 10:e0145718. [PMID: 26709916 PMCID: PMC4692528 DOI: 10.1371/journal.pone.0145718] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 12/08/2015] [Indexed: 02/08/2023] Open
Abstract
Sortase-dependent surface pili (or fimbriae) in Gram-positive bacteria are well documented as a key virulence factor for certain harmful opportunistic pathogens. However, it is only recently known that these multi-subunit protein appendages are also belonging to the “friendly” commensals and now, with this new perspective, they have come to be categorized as a niche-adaptation factor as well. In this regard, it was shown earlier that sortase-assembled piliation is a native fixture of two human intestinal commensalics (i.e., Lactobacillus rhamnosus and Bifidobacterium bifidum), and correspondingly where the pili involved have a significant role in cellular adhesion and immunomodulation processes. We now reveal that intestinal indigenous (or autochthonous) Lactobacillus ruminis is another surface-piliated commensal lactobacillar species. Heeding to in silico expectations, the predicted loci for the LrpCBA-called pili are organized tandemly in the L. ruminis genome as a canonical fimbrial operon, which then encodes for three pilin-proteins and a single C-type sortase enzyme. Through electron microscopic means, we showed that these pilus formations are a surface assemblage of tip, basal, and backbone pilin subunits (respectively named LrpC, LrpB, and LrpA) in L. ruminis, and also when expressed recombinantly in Lactococcus lactis. As well, by using the recombinant-piliated lactococci, we could define certain ecologically relevant phenotypic traits, such as the ability to adhere to extracellular matrix proteins and gut epithelial cells, but also to effectuate an induced dampening on Toll-like receptor 2 signaling and interleukin-8 responsiveness in immune-related cells. Within the context of the intestinal microcosm, by wielding such niche-advantageous cell-surface properties the LrpCBA pilus would undoubtedly have a requisite functional role in the colonization dynamics of L. ruminis indigeneity. Our study provides only the second description of a native-piliated Lactobacillus species, but at the same time also involves the structural and functional characterization of a third type of lactobacillar pilus.
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Affiliation(s)
- Xia Yu
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Annukka Jaatinen
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Johanna Rintahaka
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Ulla Hynönen
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Outi Lyytinen
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Ravi Kant
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Silja Åvall-Jääskeläinen
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Ingemar von Ossowski
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
- * E-mail: (IvO); (AP)
| | - Airi Palva
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
- * E-mail: (IvO); (AP)
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Abstract
Probiotics for the prevention of necrotizing enterocolitis have attracted a huge interest. Combined data from heterogeneous randomised controlled trials suggest that probiotics may decrease the incidence of NEC. However, the individual studies use a variety of probiotic products, and the group at greatest risk of NEC, i.e., those with a birth weight of less than 1000 g, is relatively under-represented in these trials so we do not have adequate evidence of either efficacy or safety to recommend universal prophylactic administration of probiotics to premature infants. These problems have polarized neonatologists, with some taking the view that it is unethical not to universally administer probiotics to premature infants, whereas others regard the meta-analyses as flawed and that there is insufficient evidence to recommend routine probiotic administration. Another problem is that the mechanism by which probiotics might act is not clear, although some experimental evidence is starting to accumulate. This may allow development of surrogate endpoints of effectiveness, refinement of probiotic regimes, or even development of pharmacological agents that may act through the same mechanism. Hence, although routine probiotic administration is controversial, studies of probiotic effects may ultimately lead us to effective means to prevent this devastating disease.
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Affiliation(s)
- Paul Fleming
- Homerton University Hospital, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Nigel J Hall
- Faculty of Medicine, University of Southampton, Southampton, UK
- Department of Paediatric Surgery, UCL Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London, WC1N 1EH, UK
| | - Simon Eaton
- Department of Paediatric Surgery, UCL Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London, WC1N 1EH, UK.
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Meshkibaf S, Fritz J, Gottschalk M, Kim SO. Preferential production of G-CSF by a protein-like Lactobacillus rhamnosus GR-1 secretory factor through activating TLR2-dependent signaling events without activation of JNKs. BMC Microbiol 2015; 15:238. [PMID: 26502905 PMCID: PMC4623291 DOI: 10.1186/s12866-015-0578-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 10/19/2015] [Indexed: 02/07/2023] Open
Abstract
Background Different species and strains of probiotic bacteria confer distinct immunological responses on immune cells. Lactobacillus rhamnosus GR-1 (GR-1) is a probiotic bacterial strain found in both the intestinal and urogenital tracts, and has immunomodulatory effects on several cell types including macrophages. However, detailed immunological responses and the signaling mechanism involved in the response are largely unknown. Results We examined the production of GR-1-induced cytokines/chemokines and signaling events in macrophages. Among 84 cytokines and chemokines examined, GR-1 discretely induced granulocyte colony-stimulating factor (G-CSF) mRNA at highest levels (>60-fold) without inducing other cytokines such as IL-1α, IL-1β, IL-6 and TNF-α (<5-fold). The toll-like receptor (TLR) 2/6-agonist PAM2CSK4, TLR2/1-agonist PAM3CSK4 and TLR4-agonist lipopolysaccharide induced all of these inflammatory cytokines at high levels (>50-fold). The TLR2 ligand lipoteichoic acid activated all mitogen-activated kinases, Akt and NF-κB; whereas, GR-1 selectively activated extracellular regulated kinases and p38, NF-κB and Akt, but not c-Jun N-terminal kinases (JNKs) in a TLR2-dependent manner. Using specific inhibitors, we demonstrated that lack of JNKs activation by GR-1 caused inefficient production of pro-inflammatory cytokines but not G-CSF production. A secreted heat-labile protein-like molecule, 30–100 kDa in size, induced the preferential production of G-CSF. Conclusion This study elucidated unique signaling events triggered by GR-1, resulting in selective production of the immunomodulatory cytokine G-CSF in macrophages. Electronic supplementary material The online version of this article (doi:10.1186/s12866-015-0578-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shahab Meshkibaf
- Department of Microbiology and Immunology and Infectious Diseases Research Group, Siebens-Drake Research Institute, Western University, London, ON, N6G 2 V4, Canada. .,Center for Human Immunology, Western University, London, ON, N6G 2 V4, Canada.
| | - Jӧrg Fritz
- Department of Microbiology, McGill University, Montreal, QC, H3G 0B1, Canada.
| | - Marcelo Gottschalk
- Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, J2S 2 M2, Canada.
| | - Sung Ouk Kim
- Department of Microbiology and Immunology and Infectious Diseases Research Group, Siebens-Drake Research Institute, Western University, London, ON, N6G 2 V4, Canada. .,Center for Human Immunology, Western University, London, ON, N6G 2 V4, Canada.
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