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Lopes CM, de Jesus Monteiro CS, Duarte AP, dos Santos JL. Probiotics and Prebiotics for the Treatment of Irritable Bowel Syndrome-A Narrative Review. J Clin Med 2024; 13:6337. [PMID: 39518476 PMCID: PMC11546470 DOI: 10.3390/jcm13216337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/17/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
Background/Objectives: Gastrointestinal functional disorders (GFDs), including irritable bowel syndrome (IBS), are imbalances in the gut-brain axis characterized by persistence of symptoms in the abdominal area. Probiotics are live microorganisms that provide benefits to the health of their hosts when administered in adequate amounts, while prebiotics are a substrate that is selectively used by host microorganisms. This narrative review aimed to evaluate the effectiveness of prebiotics and probiotics mostly in irritable bowel syndrome, particularly on issues such as the interaction between these products and the gut microbiota, the duration of supplementation and long-term effects, the definition of ideal dosages, and the regulation and quality control of these products. Methods: A bibliographic search was carried out in indexed databases and articles published within 10 years before the beginning of the study and publications in English language, which investigated the specific theme of the study were considered. Papers dealing with topics not covered by the research questions, or presenting errors related with the wrong population or the wrong methods, as well as experimental studies and case reviews were excluded. Fifty-five articles were selected, initially in isolation by the authors and, afterward, under consensus. Results: It was possible to observe the effectiveness mainly of probiotics, in improving specific symptoms of the respective disorder; however, the available data remain unclear due to limitations concerning samples and methods of the studies evaluated. Conclusions: Despite evidence suggestive of therapeutic efficacy, additional multicenter randomized controlled trials (RCTs) with better defined protocols are still necessary to fill in the gaps in this subject, define measures to ensure the safe administration of these products, and confirm their therapeutic potential.
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Affiliation(s)
- Carolina Marques Lopes
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal; (C.M.L.); (C.S.d.J.M.); (A.P.D.)
- CICS-UBI-Health Sciences Research Centre, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- Academic Clinical Center of Beiras, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
| | - Cristina Sofia de Jesus Monteiro
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal; (C.M.L.); (C.S.d.J.M.); (A.P.D.)
- CICS-UBI-Health Sciences Research Centre, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- Academic Clinical Center of Beiras, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- UFBI—Pharmacovigilance Unit of Beira Interior, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
| | - Ana Paula Duarte
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal; (C.M.L.); (C.S.d.J.M.); (A.P.D.)
- CICS-UBI-Health Sciences Research Centre, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- Academic Clinical Center of Beiras, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- UFBI—Pharmacovigilance Unit of Beira Interior, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
| | - Jorge Luiz dos Santos
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal; (C.M.L.); (C.S.d.J.M.); (A.P.D.)
- CICS-UBI-Health Sciences Research Centre, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- Academic Clinical Center of Beiras, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- UFBI—Pharmacovigilance Unit of Beira Interior, Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
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Chen Y, Zeng Q, Luo Y, Song M, He X, Sheng H, Gao X, Zhu Z, Sun J, Cao C. Polystyrene microplastics aggravate radiation-induced intestinal injury in mice. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 283:116834. [PMID: 39106569 DOI: 10.1016/j.ecoenv.2024.116834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 07/17/2024] [Accepted: 08/01/2024] [Indexed: 08/09/2024]
Abstract
Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 μg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients' daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.
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Affiliation(s)
- Yiyao Chen
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Qin Zeng
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yongyi Luo
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Miao Song
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Xinrong He
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hailong Sheng
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Xinna Gao
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zhenru Zhu
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Jingyuan Sun
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Chuanhui Cao
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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3
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Lennon S, Lackie T, Miltko A, Kearns ZC, Paquette MR, Bloomer RJ, Wang A, van der Merwe M. Safety and efficacy of a probiotic cocktail containing P. acidilactici and L. plantarum for gastrointestinal discomfort in endurance runners: randomized double-blinded crossover clinical trial. Appl Physiol Nutr Metab 2024; 49:890-903. [PMID: 38427981 DOI: 10.1139/apnm-2023-0449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2024]
Abstract
Probiotics are increasingly used to treat conditions associated with gastrointestinal injury and permeability, including exercise-induced gastrointestinal discomfort. This study assessed safety and efficacy of a probiotic in altering the intestinal milieu and mitigating gastrointestinal symptoms (GIS) in endurance runners. In a double blind, crossover study, 16 runners were randomized to 4 weeks of daily supplementation with a probiotic cocktail containing Pediococcus acidilactici bacteria and Lactobacillus plantarum or placebo. Fasting blood and stool samples were collected for measurement of gut permeability markers, immune parameters, and microbiome analyses. Treadmill run tests were performed before and after treatment; participants ran at 65%-70% of VO2max at 27 °C for a maximum of 90 min or until fatigue/GIS developed. A blood sample was collected after the treadmill run test. In healthy individuals, 4 weeks of probiotic supplementation did not alter health parameters, although a marginal reduction in aspartate aminotransferase levels was observed with probiotic treatment only (p = 0.05). GIS, gut permeability-associated parameters (intestinal fatty acid binding protein, lipopolysaccharide binding protein, zonulin, and cytokines), and intestinal microbial content were not altered by the probiotic supplementation. Post-run measurements of GIS and gut-associated parameters did not differ between groups; however, the observed lack of differences is confounded by an absence of measurable functional outcome as GIS was not sufficiently induced during the run. Under the current study conditions, the probiotic was safe to use, and did not affect gut- or immune-associated parameters, or intestinal symptoms in a healthy population. The probiotic might reduce tissue damage, but more studies are warranted.
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Affiliation(s)
- Sarah Lennon
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
| | - Thomas Lackie
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
| | - Adriana Miltko
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
| | - Zoey C Kearns
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
| | - Maxime R Paquette
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
| | - Richard J Bloomer
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
| | - Anyou Wang
- Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, TN 38152, USA
| | - Marie van der Merwe
- Center for Nutraceuticals and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA
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Chughtai MA, Kerimkulova MK, Mushtaq O, Hagenahalli Anand V, Rehman A, Shehryar A, Hassan B, Islam R, Islam H, Mansoor M, Rehman S. Integrated Approaches in the Management of Gastrointestinal Disorders: A Biopsychosocial Perspective. Cureus 2024; 16:e60962. [PMID: 38910693 PMCID: PMC11193854 DOI: 10.7759/cureus.60962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/25/2024] Open
Abstract
Gastrointestinal (GI) disorders, including gastroesophageal reflux disease (GERD), inflammatory bowel disease (IBD), gastritis/peptic ulcer disease (PUD), and celiac disease, significantly impact global health and economic stability. This review synthesizes current literature to elucidate the pathophysiology, clinical manifestations, diagnostic challenges, and management strategies of these prevalent conditions. Through a biopsychosocial lens, we examine the role of the gut microbiome in disease modulation and explore innovative therapeutic advancements, including microbiome-targeting interventions. The review highlights the necessity of a multidisciplinary approach to patient care, integrating medical treatment with dietary, psychological, and lifestyle modifications. By addressing these disorders holistically, the article aims to foster a deeper understanding of their biopsychosocial impacts and encourage more effective, patient-centered treatment paradigms. The findings underscore the imperative for continued research and interdisciplinary collaboration to enhance patient outcomes and reduce healthcare burdens associated with GI disorders.
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Affiliation(s)
| | | | - Omid Mushtaq
- Preventive Medicine, Sakarya University Education and Research Hospital, Sakarya, TUR
| | | | | | | | - Baran Hassan
- Internal Medicine, College of Medicine, Hawler Medical University, Erbil, IRQ
| | - Rabia Islam
- Research, Punjab Medical College, Faisalabad, PAK
| | - Hamza Islam
- Internal Medicine, Punjab Medical College, Faisalabad, PAK
| | - Muzafar Mansoor
- Internal Medicine, Allama Iqbal Medical College, Lahore, PAK
| | - Shehryar Rehman
- Internal Medicine, Al Assad University Hospital, Damascus, SYR
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5
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Lu S, Liang Y, Li L, Miao R, Liao S, Zou Y, Yang C, Ouyang D. Predicting potential microbe-disease associations based on auto-encoder and graph convolution network. BMC Bioinformatics 2023; 24:476. [PMID: 38097930 PMCID: PMC10722760 DOI: 10.1186/s12859-023-05611-7] [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: 10/25/2023] [Accepted: 12/11/2023] [Indexed: 12/17/2023] Open
Abstract
The increasing body of research has consistently demonstrated the intricate correlation between the human microbiome and human well-being. Microbes can impact the efficacy and toxicity of drugs through various pathways, as well as influence the occurrence and metastasis of tumors. In clinical practice, it is crucial to elucidate the association between microbes and diseases. Although traditional biological experiments accurately identify this association, they are time-consuming, expensive, and susceptible to experimental conditions. Consequently, conducting extensive biological experiments to screen potential microbe-disease associations becomes challenging. The computational methods can solve the above problems well, but the previous computational methods still have the problems of low utilization of node features and the prediction accuracy needs to be improved. To address this issue, we propose the DAEGCNDF model predicting potential associations between microbes and diseases. Our model calculates four similar features for each microbe and disease. These features are fused to obtain a comprehensive feature matrix representing microbes and diseases. Our model first uses the graph convolutional network module to extract low-rank features with graph information of microbes and diseases, and then uses a deep sparse Auto-Encoder to extract high-rank features of microbe-disease pairs, after which the low-rank and high-rank features are spliced to improve the utilization of node features. Finally, Deep Forest was used for microbe-disease potential relationship prediction. The experimental results show that combining low-rank and high-rank features helps to improve the model performance and Deep Forest has better classification performance than the baseline model.
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Affiliation(s)
- Shanghui Lu
- Faculty of Innovation Enginee, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, Macao Special Administrative Region of China, China
- School of Mathematics and Physics, Hechi University, No. 42, Longjiang, Hechi, 546300, Guangxi, China
| | - Yong Liang
- Faculty of Innovation Enginee, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, Macao Special Administrative Region of China, China.
- Peng Cheng Laboratory, Shenzhen, 518055, Guangdong, China.
| | - Le Li
- Faculty of Innovation Enginee, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, Macao Special Administrative Region of China, China
| | - Rui Miao
- Basic Teaching Department, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, Guangdong, China
| | - Shuilin Liao
- Faculty of Innovation Enginee, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, Macao Special Administrative Region of China, China
| | - Yongfu Zou
- School of Mathematics and Physics, Hechi University, No. 42, Longjiang, Hechi, 546300, Guangxi, China
| | - Chengjun Yang
- School of Artificial Intelligence and Manufacturing, Hechi University, No. 42, Longjiang, Hechi, 546300, Guangxi, China
| | - Dong Ouyang
- School of Biomedical Engineering, Guangdong Medical University, No. 1, Xincheng, Zhanjiang, 523808, Guangdong, China
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6
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Meade S, Liu Chen Kiow J, Massaro C, Kaur G, Squirell E, Bressler B, Lunken G. Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review. Gut Microbes 2023; 15:2287073. [PMID: 38044504 PMCID: PMC10730146 DOI: 10.1080/19490976.2023.2287073] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 11/20/2023] [Indexed: 12/05/2023] Open
Abstract
Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.
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Affiliation(s)
- Susanna Meade
- Department of Medicine, University of British Columbia, Vancouver, Canada
- IBD Centre of BC, Vancouver, Canada
| | - Jeremy Liu Chen Kiow
- Department of Medicine, University of British Columbia, Vancouver, Canada
- IBD Centre of BC, Vancouver, Canada
| | - Cristian Massaro
- Department of Pediatrics, Univerisity of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
| | - Gurpreet Kaur
- IBD Centre of BC, Vancouver, Canada
- Department of Pediatrics, Univerisity of British Columbia, Vancouver, Canada
| | - Elizabeth Squirell
- Department of Medicine, University of British Columbia, Vancouver, Canada
- IBD Centre of BC, Vancouver, Canada
| | - Brian Bressler
- Department of Medicine, University of British Columbia, Vancouver, Canada
- IBD Centre of BC, Vancouver, Canada
| | - Genelle Lunken
- IBD Centre of BC, Vancouver, Canada
- Department of Pediatrics, Univerisity of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
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Akshay A, Gasim R, Ali TE, Kumar YS, Hassan A. Unlocking the Gut-Cardiac Axis: A Paradigm Shift in Cardiovascular Health. Cureus 2023; 15:e51039. [PMID: 38264397 PMCID: PMC10805229 DOI: 10.7759/cureus.51039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2023] [Indexed: 01/25/2024] Open
Abstract
The gut-cardiac axis represents an emerging area of research focusing on the relationship between gut health and cardiovascular function. This narrative review examines the Gut-Cardiac Axis, emphasizing its emerging role in cardiovascular health and disease management. Traditionally viewed as a component of the digestive system, the gut is now recognized for its significant influence on cardiac health. The gut microbiota, its metabolites, and gut-related inflammation are key factors affecting heart structure and function. This review highlights how dietary and nutritional interventions can effectively modulate the gut-cardiac axis, leading to personalized strategies for optimizing cardiovascular health. We discuss the clinical relevance of the gut-cardiac axis, particularly its role in providing diagnostic and prognostic markers for cardiovascular diseases. This exploration of the gut-cardiac axis marks a significant shift in cardiology, integrating gut health into cardiovascular risk assessment and treatment strategies. The review provides an in-depth overview of current research and its potential to impact cardiovascular medicine significantly. We emphasize the importance of this research in advancing patient care and improving cardiac outcomes, underlining the potential of the gut-cardiac axis to transform cardiovascular health management.
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Affiliation(s)
| | - Rayan Gasim
- Internal Medicine, University of Khartoum, Khartoum, SDN
| | - Thowaiba E Ali
- Medicine and Surgery, University of Tennessee, Chattanooga, USA
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Manna L, Rizzi E, Bafile E, Cappelleri A, Ruscica M, Macchi C, Podaliri Vulpiani M, Salini R, Rossi E, Panebianco C, Perri F, Pazienza V, Federici F. Lentilactobacillus kefiri SGL 13 and Andrographis paniculata alleviate dextran sulfate sodium induced colitis in mice. Front Nutr 2023; 10:1072334. [PMID: 36860688 PMCID: PMC9968723 DOI: 10.3389/fnut.2023.1072334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 01/09/2023] [Indexed: 02/15/2023] Open
Abstract
Introduction Inflammatory bowel diseases (IBD) are chronic inflammatory conditions that typically involve diarrhea, abdominal pain, fatigue, and weight loss, with a dramatic impact on patients' quality of life. Standard medications are often associated with adverse side effects. Thus, alternative treatments such as probiotics are of great interest. The purpose of the present study was to evaluate the effects of oral administration of Lentilactobacillus kefiri (basonym: Lactobacillus kefiri) SGL 13 and Andrographis paniculata, namely, Paniculin 13™, on dextran sodium sulfate (DSS)- treated C57BL/6J mice. Methods Colitis was induced by administering 1.5% DSS in drinking water for 9 days. Forty male mice were divided into four groups, receiving PBS (control), 1.5% DSS, Paniculin 13™ and 1.5% DSS + Paniculin 13™. Results The results showed that body weight loss and Disease Activity Index (DAI) score were improved by Paniculin 13™. Moreover, Paniculin 13™ ameliorated DSS-induced dysbiosis, by modulating the gut microbiota composition. The gene expression of MPO, TNFα and iNOS in colon tissue was reduced and these data matched with the histological results, supporting the efficacy of Paniculin 13™ in reducing the inflammatory response. No adverse effects were associated to Paniculin 13™ administration. Discussion In conclusion, Paniculin 13™ could be an effective add-on approach to conventional therapies for IBD.
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Affiliation(s)
- Laura Manna
- PNK Farmaceutici S.p.a., Castelnuovo Vomano, Italy
| | | | | | - Andrea Cappelleri
- Department of Veterinary Medicine (DIMEVET), University of Milan, Milan, Italy,Mouse and Animal Pathology Laboratory (MAPLab), Fondazione UNIMI, Milan, Italy
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Chiara Macchi
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Michele Podaliri Vulpiani
- Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale” (IZSAM), Teramo, Italy
| | - Romolo Salini
- Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale” (IZSAM), Teramo, Italy
| | - Emanuela Rossi
- Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale” (IZSAM), Teramo, Italy
| | - Concetta Panebianco
- Division of Gastroenterology, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy
| | - Francesco Perri
- Division of Gastroenterology, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy
| | - Valerio Pazienza
- Division of Gastroenterology, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy
| | - Federica Federici
- PNK Farmaceutici S.p.a., Castelnuovo Vomano, Italy,*Correspondence: Federica Federici,
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Turkina SV, Statsenko ME, Tyshchenko IA. Syndrome of increased epithelial permeability: opportunities of current pharmacotherapy. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:123-132. [DOI: 10.31146/1682-8658-ecg-204-8-123-132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Syndrome of increased epithelial permeability (SPEP) is considered as one of the universal mechanisms that determine the subsequent development of chronic systemic inflammation of varying severity. Studies carried out in the last 10 years have shown the important role of SPEP in the pathogenesis of many diseases of internal organs, and, first of all, of the gastrointestinal diseases. The article discusses possible ways of correcting impaired epithelial permeability from the point of view of the cytoprotective effects of drugs most often prescribed to patients with gastrontestinal diseases.
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Liu Q, Jian W, Wang L, Yang S, Niu Y, Xie S, Hayer K, Chen K, Zhang Y, Guo Y, Tu Z. Alleviation of DSS-induced colitis in mice by a new-isolated Lactobacillus acidophilus C4. Front Microbiol 2023; 14:1137701. [PMID: 37152759 PMCID: PMC10157218 DOI: 10.3389/fmicb.2023.1137701] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 04/03/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction Probiotic is adjuvant therapy for traditional drug treatment of ulcerative colitis (UC). In the present study, Lactobacillus acidophilus C4 with high acid and bile salt resistance has been isolated and screened, and the beneficial effect of L. acidophilus C4 on Dextran Sulfate Sodium (DSS)-induced colitis in mice has been evaluated. Our data showed that oral administration of L. acidophilus C4 remarkably alleviated colitis symptoms in mice and minimized colon tissue damage. Methods To elucidate the underlying mechanism, we have investigated the levels of inflammatory cytokines and intestinal tight junction (TJ) related proteins (occludin and ZO-1) in colon tissue, as well as the intestinal microbiota and short-chain fatty acids (SCFAs) in feces. Results Compared to the DSS group, the inflammatory cytokines IL-1β, IL-6, and TNF-α in L. acidophilus C4 group were reduced, while the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were found to be elevated. In addition, proteins linked to TJ were elevated after L. acidophilus C4 intervention. Further study revealed that L. acidophilus C4 reversed the decrease in intestinal microbiota diversity caused by colitis and promoted the levels of SCFAs. Discussion This study demonstrate that L. acidophilus C4 effectively alleviated DSS-induced colitis in mice by repairing the mucosal barrier and maintaining the intestinal microecological balance. L. acidophilus C4 could be of great potential for colitis therapy.
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Affiliation(s)
- Qianqian Liu
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Wenwen Jian
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Lu Wang
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Shenglin Yang
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Yutian Niu
- International Medical College, Chongqing Medical University, Chongqing, China
| | - ShuaiJing Xie
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
| | - Kim Hayer
- Leicester Medical School, University of Leicester, Leicester, United Kingdom
| | - Kun Chen
- College of Foreign Languages, Chongqing Medical University, Chongqing, China
| | - Yi Zhang
- International Medical College, Chongqing Medical University, Chongqing, China
| | - Yanan Guo
- International Medical College, Chongqing Medical University, Chongqing, China
| | - Zeng Tu
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, China
- *Correspondence: Zeng Tu,
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Oral supplementation with selected Lactobacillus acidophilus triggers IL-17-dependent innate defense response, activation of innate lymphoid cells type 3 and improves colitis. Sci Rep 2022; 12:17591. [PMID: 36266398 PMCID: PMC9585059 DOI: 10.1038/s41598-022-21643-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 09/29/2022] [Indexed: 01/13/2023] Open
Abstract
Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that is illustrated by improvement of intestinal inflammation and antimicrobial activity against several pathogens. In this study, we evaluated the immunomodulatory properties of the L. acidophilus strain BIO5768 at steady state and upon acute inflammation. Supplementation of naïve mice with BIO5768 heightened the transcript level of some IL-17 target genes encoding for protein with microbicidal activity independently of NOD2 signaling. Of these, the BIO5768-induced expression of Angiogenin-4 was blunted in monocolonized mice that are deficient for the receptor of IL-17 (but not for NOD2). Interestingly, priming of bone marrow derived dendritic cells by BIO5768 enhanced their ability to support the secretion of IL-17 by CD4+ T cells. Equally of importance, the production of IL-22 by type 3 innate lymphoid cells is concomitantly heightened in response to BIO5768. When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was able to alleviate at least partially intestinal inflammation induced by Citrobacter rodentium infection. Furthermore, BIO5768 was also able to improve colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In conclusion, we identify a new potential probiotic strain for the management of inflammatory bowel diseases, and provide some insights into its IL-17-dependent and independent mode of action.
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12
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Gan D, Chen J, Tang X, Xiao L, Martoni CJ, Leyer G, Huang G, Li W. Impact of a probiotic chewable tablet on stool habits and microbial profile in children with functional constipation: A randomized controlled clinical trial. Front Microbiol 2022; 13:985308. [PMID: 36071965 PMCID: PMC9441913 DOI: 10.3389/fmicb.2022.985308] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Constipation is a common and typically multifactorial childhood complaint, and the clinical management of childhood functional constipation (FC) is challenging. A randomized, single-blind, placebo-controlled, multi-center clinical trial was conducted in 92 children (47 from Beijing, China and 45 from Shanghai, China) aged 4–12 with FC according to Rome III criteria. Children were assigned to receive a probiotic chewable tablet (5 × 109 CFU/day, n = 47), consisting of Lactobacillus acidophilus DDS-1® and Bifidobacterium animalis subsp. lactis UABla-12™ or placebo (n = 45), twice daily for 4 weeks, followed by a week follow-up period. Results suggested that the probiotic group showed a faster and more pronounced normalization of stool frequency over the intervention period (3.15 vs. 1.83) when compared to placebo group (2.51 vs. 1.87). Meanwhile, the percentage of subjects with hard defecation decreased from 43 to 14% in the probiotic group, while the percentage of subjects with normal defecation increased from 56 to 80% in the probiotic group, further confirming the normalization of stools habits. This randomized controlled trial demonstrated the potential of a probiotic chewable tablet containing L. acidophilus DDS-1® and B. Lactis UABla-12™ as a daily probiotic dosage form for children with FC.
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Affiliation(s)
- Dan Gan
- Sirio Pharma Co., Ltd., Shantou, China
- *Correspondence: Dan Gan,
| | | | - Xin Tang
- Sirio Pharma Co., Ltd., Shantou, China
| | - Luyao Xiao
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | | | | | | | - Wei Li
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
- Wei Li,
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13
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de Negreiros LMV, Pascoal LB, Genaro LM, Silva JF, Rodrigues BL, Camargo MG, Martinez CAR, Coy CSR, Ayrizono MDLS, Fagundes JJ, Leal RF. Pouchitis: insight into the pathogenesis and clinical aspects. Am J Transl Res 2022; 14:4406-4425. [PMID: 35958439 PMCID: PMC9360866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 05/26/2022] [Indexed: 06/15/2023]
Abstract
Ulcerative colitis (UC) is a chronic intestinal inflammatory disease and familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease. Both diseases, despite being different, may require the same surgical procedure: proctocolectomy with ileal pouch-anal anastomosis (IPAA). The main complication after this procedure is pouch inflammation (pouchitis). This inflammatory complication can affect up to 60 percent of patients who receive IPAA for UC, and a very small percentage of the FAP patients. The purpose of this review was to determine the current molecular mechanisms in its pathogenesis and detail the risk factors involved in pouchitis, its diagnosis, and treatment.
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Affiliation(s)
- Leandro Minatel Vidal de Negreiros
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Lívia Bitencourt Pascoal
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Lívia Moreira Genaro
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Julian Furtado Silva
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Michel Gardere Camargo
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Carlos Augusto Real Martinez
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Cláudio Saddy Rodrigues Coy
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - João José Fagundes
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp) Campinas, Brazil
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14
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Cell-free probiotic supernatant (CFS) treatment alleviates indomethacin-induced enterocolopathy in BALB/c mice by down-modulating inflammatory response and oxidative stress: potential alternative targeted treatment. Inflammopharmacology 2022; 30:1685-1703. [PMID: 35505268 DOI: 10.1007/s10787-022-00996-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/08/2022] [Indexed: 11/05/2022]
Abstract
Probiotics and their metabolites appear to be a promising approach that targets both the intestinal inflammation and dysbiosis in bowel diseases. In this context, the emergence of the probiotic cell-free supernatant (CFS) has attracted more attention as a safe and targeted alternative therapy with reduced side effects. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause significant intestinal alterations and inflammation, leading to experimental enterocolopathy resembling Crohn disease. Therefore, we investigated the effect of CFS supplementation on the inflammation and the mucosal intestinal alterations induced by NSAIDs, indomethacin. In the current study, a murine model of intestinal inflammation was generated by the oral gavage (o.g) of indomethacin (10 mg/kg) to BALB/C mice. A group of mice treated with indomethacin was concomitantly treated orally by CFS for 5 days. The Body Health Condition index was monitored, and histological scores were evaluated. Moreover, oxidative and pro-inflammatory markers were assessed. Interestingly, we observed that CFS treatment attenuated the severity of the intestinal inflammation in our enterocolopathy model and resulted in the improvement of the clinical symptoms and the histopathological features. Notably, nitric oxide, tumor necrosis factor alpha, malondialdehyde, and myeloperoxidase levels were down-modulated by CFS supplementation. Concomitantly, an attenuation of NF-κB p65, iNOS, COX2 expression in the ileum and the colon was reported. Collectively, our data suggest that CFS treatment has a beneficial effect in experimental enterocolopathy model and could constitute a good therapeutic candidate for alleviating inflammatory responses and to maintain mucosal homeostasis during chronic and severe conditions of intestinal inflammation.
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15
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Hazan S, Stollman N, Bozkurt HS, Dave S, Papoutsis AJ, Daniels J, Barrows BD, Quigley EM, Borody TJ. Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity. BMJ Open Gastroenterol 2022; 9:bmjgast-2022-000871. [PMID: 35483736 PMCID: PMC9051551 DOI: 10.1136/bmjgast-2022-000871] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 03/28/2022] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls. DESIGN Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels. RESULTS Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria. CONCLUSION We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention. TRIAL REGISTRATION NUMBER NCT04031469 (PCR-) and 04359836 (PCR+).
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Affiliation(s)
| | - Neil Stollman
- Division of Gastroenterology, Alta Bates Summit Medical Center, Berkeley, California, USA
| | - Huseyin S Bozkurt
- Clinic of Gastroenterology, Istanbul Maltepe University, Istanbul, Turkey
| | - Sonya Dave
- N/A, Microbiome Research, Inc, Ventura, California, USA.,Medical Writing and Biostatistics, North End Advisory, Smyrna, Georgia, USA
| | | | | | | | - Eamonn Mm Quigley
- Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA
| | - Thomas J Borody
- N/A, Centre for Digestive Diseases, Five Dock, New South Wales, Australia
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16
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Inactivation of the Pyrimidine Biosynthesis pyrD Gene Negatively Affects Biofilm Formation and Virulence Determinants in the Crohn’s Disease-Associated Adherent Invasive Escherichia coli LF82 Strain. Microorganisms 2022; 10:microorganisms10030537. [PMID: 35336113 PMCID: PMC8956108 DOI: 10.3390/microorganisms10030537] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/17/2022] [Accepted: 02/26/2022] [Indexed: 01/07/2023] Open
Abstract
In Crohn’s disease (CD) patients, the adherent-invasive Escherichia coli (AIEC) pathovar contributes to the chronic inflammation typical of the disease via its ability to invade gut epithelial cells and to survive in macrophages. We show that, in the AIEC strain LF82, inactivation of the pyrD gene, encoding dihydroorotate dehydrogenase (DHOD), an enzyme of the de novo pyrimidine biosynthetic pathway, completely abolished its ability of to grow in a macrophage environment-mimicking culture medium. In addition, pyrD inactivation reduced flagellar motility and strongly affected biofilm formation by downregulating transcription of both type 1 fimbriae and curli subunit genes. Thus, the pyrD gene appears to be essential for several cellular processes involved in AIEC virulence. Interestingly, vidofludimus (VF), a DHOD inhibitor, has been proposed as an effective drug in CD treatment. Despite displaying a potentially similar binding mode for both human and E. coli DHOD in computational molecular docking experiments, VF showed no activity on either growth or virulence-related processes in LF82. Altogether, our results suggest that the crucial role played by the pyrD gene in AIEC virulence, and the presence of structural differences between E. coli and human DHOD allowing for the design of specific inhibitors, make E. coli DHOD a promising target for therapeutical strategies aiming at counteracting chronic inflammation in CD by acting selectively on its bacterial triggers.
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17
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Jeon S, Kim H, Kim J, Seol D, Jo J, Choi Y, Cho S, Kim H. Positive Effect of Lactobacillus acidophilus EG004 on Cognitive Ability of Healthy Mice by Fecal Microbiome Analysis Using Full-Length 16S-23S rRNA Metagenome Sequencing. Microbiol Spectr 2022; 10:e0181521. [PMID: 35019699 PMCID: PMC8754107 DOI: 10.1128/spectrum.01815-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 12/07/2021] [Indexed: 11/20/2022] Open
Abstract
Evidence for the concept of the "gut-brain axis" (GBA) has risen. Many types of research demonstrated the mechanism of the GBA and the effect of probiotic intake. Although many studies have been reported, most were focused on neurodegenerative disease and, it is still not clear what type of bacterial strains have positive effects. We designed an experiment to discover a strain that positively affects brain function, which can be recognized through changes in cognitive processes using healthy mice. The experimental group consisted of a control group and three probiotic consumption groups, namely, Lactobacillus acidophilus, Lacticaseibacillus paracasei, and Lacticaseibacillus rhamnosus. Three experimental groups fed probiotics showed an improved cognitive ability by cognitive-behavioral tests, and the group fed on L. acidophilus showed the highest score. To provide an understanding of the altered microbial composition effect on the brain, we performed full 16S-23S rRNA sequencing using Nanopore, and operational taxonomic units (OTUs) were identified at species level. In the group fed on L. acidophilus, the intestinal bacterial ratio of Firmicutes and Proteobacteria phyla increased, and the bacterial proportions of 16 species were significantly different from those of the control group. We estimated that the positive results on the cognitive behavioral tests were due to the increased proportion of the L. acidophilus EG004 strain in the subjects' intestines since the strain can produce butyrate and therefore modulate neurotransmitters and neurotrophic factors. We expect that this strain expands the industrial field of L. acidophilus and helps understand the mechanism of the gut-brain axis. IMPORTANCE Recently, the concept of the "gut-brain axis" has risen and suggested that microbes in the GI tract affect the brain by modulating signal molecules. Although many pieces of research were reported in a short period, a signaling mechanism and the effects of a specific bacterial strain are still unclear. Besides, since most of the research was focused on neurodegenerative disease, the study with a healthy animal model is still insufficient. In this study, we show using a healthy animal model that a bacterial strain (Lactobacillus acidophilus EG004) has a positive effect on mouse cognitive ability. We experimentally verified an improved cognitive ability by cognitive behavioral tests. We performed full 16S-23S rRNA sequencing using a Nanopore MinION instrument and provided the gut microbiome composition at the species level. This microbiome composition consisted of candidate microbial groups as a biomarker that shows positive effects on cognitive ability. Therefore, our study suggests a new perspective for probiotic strain use applicable for various industrialization processes.
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Affiliation(s)
- Soomin Jeon
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Hyaekang Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Jina Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Donghyeok Seol
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
- eGnome, Inc., Seoul, Republic of Korea
| | - Jinchul Jo
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Youngseok Choi
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Seoae Cho
- eGnome, Inc., Seoul, Republic of Korea
| | - Heebal Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
- eGnome, Inc., Seoul, Republic of Korea
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea
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18
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Wu H, Lam TYC, Shum TF, Tsai TY, Chiou J. Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration. Hypertens Res 2022; 45:270-282. [PMID: 34857899 PMCID: PMC8766282 DOI: 10.1038/s41440-021-00796-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 09/30/2021] [Accepted: 10/07/2021] [Indexed: 12/11/2022]
Abstract
The role of the gut microbiota in various metabolic diseases has been widely studied. This study aims to test the hypothesis that gut microbiota dysbiosis is associated with DOCA-salt-induced hypertension, while captopril, an antihypertensive drug, is able to rebalance the gut microbiota alterations caused by hypertension. Treatment with captopril resulted in an approximate 32 mmHg reduction in systolic blood pressure (162.57 vs. 194.61 mmHg) in DOCA-salt-induced hypertensive rats, although it was significantly higher than that in SHAM rats (136.10 mmHg). Moreover, the nitric oxide (NO) level was significantly increased (20.60 vs. 6.42 µM) while the angiotensin II (Ang II) content (42.40 vs. 59.47 pg/ml) was attenuated nonsignificantly by captopril treatment in comparison to those of DOCA-salt-induced hypertensive rats. The introduction of captopril significantly decreased the levels of tumor necrosis factor-α (TNF-ɑ) and interleukin-6 (IL-6). Hypertrophy and fibrosis in kidneys and hearts were also significantly attenuated by captopril. Furthermore, gut microbiota dysbiosis was observed in DOCA-salt-induced hypertensive rats. The abundances of several phyla and genera, including Proteobacteria, Cyanobacteria, Escherichia-Shigella, Eubacterium nodatum and Ruminococcus, were higher in DOCA-salt-induced hypertensive rats than in SHAM rats, while these changes were reversed by captopril treatment. Of particular interest, the genera Bifidobacterium and Akkermansia, reported as beneficial bacteria in the gut, were abundant in only hypertensive rats treated with captopril. These results provide evidence that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt-induced hypertensive rats, suggesting that the alteration of the gut flora by captopril may contribute to the hypotensive effect of this drug.
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Affiliation(s)
- Haicui Wu
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Theo Y C Lam
- Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Tim-Fat Shum
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Tsung-Yu Tsai
- Department of Food Science, Fu Jen Catholic University, New Taipei City, 24205, Taiwan
| | - Jiachi Chiou
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
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19
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Son S, Lee R, Park SM, Lee SH, Lee HK, Kim Y, Shin D. Complete genome sequencing and comparative genomic analysis of Lactobacillus acidophilus C5 as a potential canine probiotics. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2021; 63:1411-1422. [PMID: 34957454 PMCID: PMC8672248 DOI: 10.5187/jast.2021.e126] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/22/2021] [Accepted: 11/12/2021] [Indexed: 11/20/2022]
Abstract
Lactobacillus acidophilus is a gram-positive, microaerophilic, and acidophilic bacterial species. L. acidophilus strains in the gastrointestinal tracts of humans and other animals have been profiled, but strains found in the canine gut have not been studied yet. Our study helps in understanding the genetic features of the L. acidophilus C5 strain found in the canine gut, determining its adaptive features evolved to survive in the canine gut environment, and in elucidating its probiotic functions. To examine the canine L. acidophilus C5 genome, we isolated the C5 strain from a Korean dog and sequenced it using PacBio SMRT sequencing technology. A comparative genomic approach was used to assess genetic relationships between C5 and six other strains and study the distinguishing features related to different hosts. We found that most genes in the C5 strain were related to carbohydrate transport and metabolism. The pan-genome of seven L. acidophilus strains contained 2,254 gene families, and the core genome contained 1,726 gene families. The phylogenetic tree of the core genes in the canine L. acidophilus C5 strain was very close to that of two strains (DSM20079 and NCFM) from humans. We identified 30 evolutionarily accelerated genes in the L. acidophilus C5 strain in the ratio of non-synonymous to synonymous substitutions (dN/dS) analysis. Five of these thirty genes were associated with carbohydrate transport and metabolism. This study provides insights into genetic features and adaptations of the L. acidophilus C5 strain to survive the canine intestinal environment. It also suggests that the evolution of the L. acidophilus genome is closely related to the host's evolutionary adaptation process.
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Affiliation(s)
- Seungwoo Son
- Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju 54896, Korea
| | - Raham Lee
- Department of Animal Biotechnology, College of Agricultural and Life Sciences, Jeonbuk National University, Jeonju 54896, Korea
| | - Seung-Moon Park
- Department of Bioenvironmental Chemistry, College of Agriculture and Life Sciences, Jeonbuk National University, Jeonju 54896, Korea
| | | | - Hak-Kyo Lee
- Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju 54896, Korea.,Department of Animal Biotechnology, College of Agricultural and Life Sciences, Jeonbuk National University, Jeonju 54896, Korea
| | - Yangseon Kim
- Center for Industrialization of Agriculture and Livestock Microorganism, Jeongeup 56212, Korea
| | - Donghyun Shin
- Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju 54896, Korea
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20
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Denktaş C, Yilmaz Baysoy D, Bozdoğan A, Bozkurt HS, Bozkurt K, Özdemir O, Yilmaz M. Development and characterization of sodium alginate/
bifidobacterium probiotic
biohybrid material used in tissue engineering. J Appl Polym Sci 2021. [DOI: 10.1002/app.52086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Cenk Denktaş
- Faculty of Arts and Sciences, Physics Department Yildiz Technical University Istanbul Turkey
| | | | - Altan Bozdoğan
- Faculty of Arts and Sciences, Physics Department Yildiz Technical University Istanbul Turkey
| | - Hüseyin Sancar Bozkurt
- Maltepe University Medicine Faculty Internal Medicine, Clinic of Gastroenterology Istanbul Turkey
| | - Kutsal Bozkurt
- Faculty of Arts and Sciences, Physics Department Yildiz Technical University Istanbul Turkey
| | - Orhan Özdemir
- Faculty of Arts and Sciences, Physics Department Yildiz Technical University Istanbul Turkey
| | - Mehmet Yilmaz
- Faculty of Arts and Sciences, Physics Department Yildiz Technical University Istanbul Turkey
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21
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Pagnini C, Di Paolo MC, Graziani MG, Delle Fave G. Probiotics and Vitamin D/Vitamin D Receptor Pathway Interaction: Potential Therapeutic Implications in Inflammatory Bowel Disease. Front Pharmacol 2021; 12:747856. [PMID: 34899302 PMCID: PMC8657408 DOI: 10.3389/fphar.2021.747856] [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] [Received: 07/26/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology and immunomediated pathogenesis. In the last years, the comprehension of the complex mechanisms involved in the intestinal mucosal homeostasis, and the analysis of the alterations potentially leading to inflammatory pathologic states, has consistently increased. Specifically, the extraordinary impulse in the field of research of the intestinal microbiome has opened the door to the investigation of possible novel approaches to the diagnosis, management and therapeutic applications in IBD. In line with that, administration of probiotic bacteria has been intensely evaluated, leading to much more exciting results in experimental models than in clinical practice. Considering the consistent heterogeneity of the available studies on probiotics, the increased knowledge of the properties of the single bacterial species would ideally lead to unravel potential mechanisms of action that may bring therapeutic applications in specific pathologic condition. Among the relevant molecular pathways for mucosal homeostasis maintenance, the vitamin D/vitamin D receptor (VDR) pathway has been intensely studied in the very last years. In fact, besides osteometabolic functions, the vitamin D exerts important homeostatic effects in the organism at multiple levels, such as immunomodulation, inflammation control, and microbiota regulation, which are likely to play a relevant role in intestinal mucosa protection. In the present review, recent findings about probiotic applications in IBD and mechanisms of action linking vitamin D/VDR pathway to IBD are reported. Available evidence for probiotic effect on vitamin D/VDR are reviewed and potential future application in IBD patients are discussed. At present, many aspects of IBD pathogenesis are still obscure, and current therapeutic options for IBD treatment are at best suboptimal. The increasing comprehension of the different pathways involved in IBD pathogenesis will lead to novel findings ideally leading to potential clinical applications. Microbiota manipulation and vitamin/VDR pathway appear a promising field for future research and therapeutic developments.
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Affiliation(s)
- Cristiano Pagnini
- Gastroenterologia ed Endoscopia Digestiva, AO S. Giovanni Addolorata, Rome, Italy
| | - Maria Carla Di Paolo
- Gastroenterologia ed Endoscopia Digestiva, AO S. Giovanni Addolorata, Rome, Italy
| | | | - Gianfranco Delle Fave
- Gastroenterologia, Università "Sapienza", Rome, Italy.,Onlus "S. Andrea", Rome, Italy
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22
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Gut Microbial Metabolite-Mediated Regulation of the Intestinal Barrier in the Pathogenesis of Inflammatory Bowel Disease. Nutrients 2021; 13:nu13124259. [PMID: 34959809 PMCID: PMC8704337 DOI: 10.3390/nu13124259] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/20/2021] [Accepted: 11/25/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease. The disease has a multifactorial aetiology, involving genetic, microbial as well as environmental factors. The disease pathogenesis operates at the host-microbe interface in the gut. The intestinal epithelium plays a central role in IBD disease pathogenesis. Apart from being a physical barrier, the epithelium acts as a node that integrates environmental, dietary, and microbial cues to calibrate host immune response and maintain homeostasis in the gut. IBD patients display microbial dysbiosis in the gut, combined with an increased barrier permeability that contributes to disease pathogenesis. Metabolites produced by microbes in the gut are dynamic indicators of diet, host, and microbial interplay in the gut. Microbial metabolites are actively absorbed or diffused across the intestinal lining to affect the host response in the intestine as well as at systemic sites via the engagement of cognate receptors. In this review, we summarize insights from metabolomics studies, uncovering the dynamic changes in gut metabolite profiles in IBD and their importance as potential diagnostic and prognostic biomarkers of disease. We focus on gut microbial metabolites as key regulators of the intestinal barrier and their role in the pathogenesis of IBD.
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Ren R, Gao X, Shi Y, Li J, Peng L, Sun G, Wang Z, Yan B, Zhi J, Yang Y. Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria. Front Microbiol 2021; 12:742255. [PMID: 34867859 PMCID: PMC8635752 DOI: 10.3389/fmicb.2021.742255] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 10/07/2021] [Indexed: 12/26/2022] Open
Abstract
Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria. Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT. Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group. Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.
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Affiliation(s)
- Rongrong Ren
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xuefeng Gao
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, China
- Central Laboratory, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen, China
| | - Yichao Shi
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Jianfeng Li
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Gang Sun
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zikai Wang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Junli Zhi
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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Baral KC, Bajracharya R, Lee SH, Han HK. Advancements in the Pharmaceutical Applications of Probiotics: Dosage Forms and Formulation Technology. Int J Nanomedicine 2021; 16:7535-7556. [PMID: 34795482 PMCID: PMC8594788 DOI: 10.2147/ijn.s337427] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Probiotics have demonstrated their high potential to treat and/or prevent various diseases including neurodegenerative disorders, cancers, cardiovascular diseases, and inflammatory diseases. Probiotics are also effective against multidrug-resistant pathogens and help maintain a balanced gut microbiota ecosystem. Accordingly, the global market of probiotics is growing rapidly, and research efforts to develop probiotics into therapeutic adjuvants are gaining momentum. However, because probiotics are living microorganisms, many biological and biopharmaceutical barriers limit their clinical application. Probiotics may lose their activity in the harsh gastric conditions of the stomach or in the presence of bile salts. Moreover, they easily lose their viability under thermal or oxidative stress during their preparation and storage. Therefore, stable formulations of probiotics are required to overcome the various physicochemical, biopharmaceutical, and biological barriers and to maximize their therapeutic effectiveness and clinical applicability. This review provides an overview of the pharmaceutical applications of probiotics and covers recent formulation approaches to optimize the delivery of probiotics with particular emphasis on various dosage forms and formulation technologies.
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Affiliation(s)
- Kshitis Chandra Baral
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
| | - Rajiv Bajracharya
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
| | - Sang Hoon Lee
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
| | - Hyo-Kyung Han
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
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Understanding the physiology of human defaecation and disorders of continence and evacuation. Nat Rev Gastroenterol Hepatol 2021; 18:751-769. [PMID: 34373626 DOI: 10.1038/s41575-021-00487-5] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field.
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Benjak Horvat I, Gobin I, Kresović A, Hauser G. How can probiotic improve irritable bowel syndrome symptoms? World J Gastrointest Surg 2021; 13:923-940. [PMID: 34621470 PMCID: PMC8462084 DOI: 10.4240/wjgs.v13.i9.923] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/22/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
The onset and manifestations of irritable bowel syndrome (IBS) is associated with several factors, and the pathophysiology involves various central and peripheral mechanisms. Most studies indicate that the management of gut microbiota could significantly affect the improvement of subjective disorders in patients with IBS. Numerous clinical trials have assessed the efficacy of probiotics for IBS with controversial conclusions. Several clinical trials have suggested that probiotics can improve global IBS symptoms, while others only improve individual IBS symptoms, such as bloating scores and abdominal pain scores. Only a few clinical trials have found no apparent effect of probiotics on IBS symptoms. Generally, probiotics appear to be safe for patients with IBS. However, the question of which probiotics should be used for certain IBS subtypes remains unresolved. In everyday practice, the dose of the recommended probiotic remains questionable, as well as how long the probiotic should be used in therapy. The use of probiotics in the M subtype and non-classified IBS is particularly problematic, in which combination therapy should be recommended due to the change in symptoms. Therefore, new approaches are needed in the design of clinical studies that should address certain subtypes of IBS.
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Affiliation(s)
- Indira Benjak Horvat
- Department of Gastroenterology, Varaždin General Hospital, Varažin 42000, Croatia
| | - Ivana Gobin
- Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Andrea Kresović
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Goran Hauser
- Department of Gastroenterology, Faculty of Medicine, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka 51000, Croatia
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Calatayud M, Verstrepen L, Ghyselinck J, Van den Abbeele P, Marzorati M, Modica S, Ranjanoro T, Maquet V. Chitin Glucan Shifts Luminal and Mucosal Microbial Communities, Improve Epithelial Barrier and Modulates Cytokine Production In Vitro. Nutrients 2021; 13:nu13093249. [PMID: 34579126 PMCID: PMC8467507 DOI: 10.3390/nu13093249] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/13/2021] [Accepted: 09/17/2021] [Indexed: 12/15/2022] Open
Abstract
The human gut microbiota has been linked to the health status of the host. Modulation of human gut microbiota through pro- and prebiotic interventions has yielded promising results; however, the effect of novel prebiotics, such as chitin-glucan, on gut microbiota-host interplay is still not fully characterized. We assessed the effect of chitin-glucan (CG) and chitin-glucan plus Bifidobacterium breve (CGB) on human gut microbiota from the luminal and mucosal environments in vitro. Further, we tested the effect of filter-sterilized fecal supernatants from CG and CGB fermentation for protective effects on inflammation-induced barrier disruption and cytokine production using a co-culture of enterocytes and macrophage-like cells. Overall, CG and CGB promote health-beneficial short-chain fatty acid production and shift human gut microbiota composition, with a consistent effect increasing Roseburia spp. and butyrate producing-bacteria. In two of three donors, CG and CGB also stimulated Faecalibacterium prausniitzi. Specific colonization of B. breve was observed in the lumen and mucosal compartment; however, no synergy was detected for different endpoints when comparing CGB and CG. Both treatments included a significant improvement of inflammation-disrupted epithelial barrier and shifts on cytokine production, especially by consistent increase in the immunomodulatory cytokines IL10 and IL6.
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Affiliation(s)
- Marta Calatayud
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (L.V.); (J.G.); (P.V.d.A.)
- Center for Microbial Ecology and Technology (CMET), Ghent University, Coupure Links 653, 9052 Ghent, Belgium
- Correspondence: (M.C.); or (M.M.)
| | - Lynn Verstrepen
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (L.V.); (J.G.); (P.V.d.A.)
| | - Jonas Ghyselinck
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (L.V.); (J.G.); (P.V.d.A.)
| | | | - Massimo Marzorati
- ProDigest BV, Technologiepark 82, 9052 Ghent, Belgium; (L.V.); (J.G.); (P.V.d.A.)
- Center for Microbial Ecology and Technology (CMET), Ghent University, Coupure Links 653, 9052 Ghent, Belgium
- Correspondence: (M.C.); or (M.M.)
| | - Salvatore Modica
- KitoZyme SA., Parc Industriel des Hauts Sarts, 4040 Herstal, Belgium; (S.M.); (T.R.); (V.M.)
| | - Thibaut Ranjanoro
- KitoZyme SA., Parc Industriel des Hauts Sarts, 4040 Herstal, Belgium; (S.M.); (T.R.); (V.M.)
| | - Véronique Maquet
- KitoZyme SA., Parc Industriel des Hauts Sarts, 4040 Herstal, Belgium; (S.M.); (T.R.); (V.M.)
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Zhang XF, Guan XX, Tang YJ, Sun JF, Wang XK, Wang WD, Fan JM. Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis. Eur J Nutr 2021; 60:2855-2875. [PMID: 33555375 DOI: 10.1007/s00394-021-02503-5] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 01/22/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. Furthermore, the changes of gut microbiota in IBD's patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD. METHODS The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD's remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described. RESULTS Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD's remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26, P < 0.05; SMD = 1.00, 95% CI 0.27, 1.73, P < 0.05). In subgroup analyses of IBD remission rate and UC disease activity index, we obtained some statistically significant results in some subgroup (P < 0.05). To some extent, probiotic supplements can increase the number of beneficial bacteria (especially Bifidobacteria) in the intestinal tract of patients with IBD. CONCLUSIONS Our results support the treatment of IBD (especially UC) with pro/pre/synbiotics, and synbiotics are more effective. Probiotic supplements that are based on Lactobacillus and Bifidobacterium or more than one strain are more likely to be beneficial for IBD remission. The dose of 1010-1012 CFU/day may be a reference range for using probiotics to relieve IBD.
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Affiliation(s)
- Xiao-Feng Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China
| | - Xiao-Xian Guan
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China
| | - Yu-Jun Tang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China
| | - Jin-Feng Sun
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China
| | - Xiao-Kai Wang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China
| | - Wei-Dong Wang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China
| | - Jian-Ming Fan
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.
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Cavuoto KM, Galor A, Banerjee S. Ocular Surface Microbiome Alterations Are Found in Both Eyes of Individuals With Unilateral Infectious Keratitis. Transl Vis Sci Technol 2021; 10:19. [PMID: 34003904 PMCID: PMC7884290 DOI: 10.1167/tvst.10.2.19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose To analyze the ocular surface microbiome (OSM) profile in both eyes of individuals with unilateral keratitis. Methods In this prospective, cross-sectional study, the conjunctival OSM of adults (>18 years old) presenting to an ophthalmic emergency department with acute unilateral keratitis and controls without an acute infectious process was sampled. Samples underwent DNA amplification and 16S sequencing using Illumina MiSeq 250 and were analyzed using Qiime. Statistical analysis was performed using a two-sided Student t-test, diversity indices, and principal coordinate analysis. The main outcome measures included relative abundance and α and β diversity. Results Bacterial DNA was recovered from all 34 eyes of 17 individuals with keratitis (mean age, 49.3 ± 17.5 years) and 16 eyes of controls (mean age, 56.6 ± 17.0 years). In the two culture-positive eyes, 16S aligned with culture results. Significant differences in α diversities were noted when comparing both eyes of individuals with keratitis to control eyes (all P < 0.05), but no significant differences between the eyes of an individual with keratitis. Principal coordinate analysis plots confirmed this finding, demonstrating separation between either eye of patients with keratitis and controls (both P < 0.01), however not between eyes in patients with unilateral keratitis. Both eyes of individuals with keratitis had greater abundance of Pseudomonas compared with controls both on compositional analysis and linear discriminant analysis. Conclusions Alterations in the OSM profile are detected in both eyes of individuals with unilateral keratitis compared with controls. Beyond the causative organism, a greater abundance of potential pathogens and lesser abundance of commensal organisms were found. Translational Relevance The OSM profile is altered in both eyes of individuals with unilateral keratitis, which may lend insight into the role of the microbiome in the pathophysiology of disease.
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Affiliation(s)
- Kara M Cavuoto
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Anat Galor
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.,Miami Veterans Administration Medical Center, Miami, FL, USA
| | - Santanu Banerjee
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.,Center for Scientific Review, National Institutes of Health, Bethesda, MD, USA
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Torun A, Hupalowska A, Trzonkowski P, Kierkus J, Pyrzynska B. Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children. Front Immunol 2021; 12:642166. [PMID: 34163468 PMCID: PMC8215716 DOI: 10.3389/fimmu.2021.642166] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 05/24/2021] [Indexed: 12/12/2022] Open
Abstract
The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.
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Affiliation(s)
- Anna Torun
- Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland
| | - Anna Hupalowska
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, United States
| | - Piotr Trzonkowski
- Department of Medical Immunology, Medical University of Gdansk, Gdansk, Poland
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Beata Pyrzynska
- Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland
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Dumas A, Knaus UG. Raising the 'Good' Oxidants for Immune Protection. Front Immunol 2021; 12:698042. [PMID: 34149739 PMCID: PMC8213335 DOI: 10.3389/fimmu.2021.698042] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022] Open
Abstract
Redox medicine is a new therapeutic concept targeting reactive oxygen species (ROS) and secondary reaction products for health benefit. The concomitant function of ROS as intracellular second messengers and extracellular mediators governing physiological redox signaling, and as damaging radicals instigating or perpetuating various pathophysiological conditions will require selective strategies for therapeutic intervention. In addition, the reactivity and quantity of the oxidant species generated, its source and cellular location in a defined disease context need to be considered to achieve the desired outcome. In inflammatory diseases associated with oxidative damage and tissue injury, ROS source specific inhibitors may provide more benefit than generalized removal of ROS. Contemporary approaches in immunity will also include the preservation or even elevation of certain oxygen metabolites to restore or improve ROS driven physiological functions including more effective redox signaling and cell-microenvironment communication, and to induce mucosal barrier integrity, eubiosis and repair processes. Increasing oxidants by host-directed immunomodulation or by exogenous supplementation seems especially promising for improving host defense. Here, we summarize examples of beneficial ROS in immune homeostasis, infection, and acute inflammatory disease, and address emerging therapeutic strategies for ROS augmentation to induce and strengthen protective host immunity.
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Affiliation(s)
- Alexia Dumas
- Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland
| | - Ulla G Knaus
- Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland
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Chen J, Wang A, Wang Q. Dysbiosis of the gut microbiome is a risk factor for osteoarthritis in older female adults: a case control study. BMC Bioinformatics 2021; 22:299. [PMID: 34082693 PMCID: PMC8173911 DOI: 10.1186/s12859-021-04199-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/12/2021] [Indexed: 11/10/2022] Open
Abstract
Background Osteoarthritis (OA) is a multifactorial joint degenerative disease with low-grade inflammation. The gut microbiome has recently emerged as an pathogenic factor of OA, and prebiotics supplementation could alleviate OA symptoms in animal models. However, the relationship between the gut microbiome and OA in the older female adults is hitherto not clear. Results Here we studied the gut microbiome of 57 OA patients and their healthy controls by metagenome-wide association study based on previously published data. A significant reduction in the richness and diversity of gut microbiome were observed in OA patients. Bifidobacterium longum and Faecalibacterium prausnitzii were decreased while Clostridium spp. was increased in the OA group. The functional modules, particularly the energetic metabolism and acetate production were also decreased in the OA patients. To evaluate the diagnostic value of identified species for elderly patients with OA, we constructed a set of random forest disease classifiers based on species differences between the two groups. Among them, 9 species reached the lowest classification error in the random forest cross validation, and the area under ROC of the model was 0.81. Conclusions Significant alterations in the gut microbial composition and function were observed between the older patients with OA and their controls, and a random forest classifier model for OA were constructed based on the differences in our study. Our study have identified several potential gut microbial targets in the elderly females with OA, which will facilitate the treatment of OA based on gut microbiota, is of great value in alleviating pain and improving the quality of life for them. Supplementary Information The online version contains supplementary material available at 10.1186/s12859-021-04199-0.
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Affiliation(s)
- Juanjuan Chen
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, People's Republic of China
| | - Anqi Wang
- Institute of Clinical Research and Translational Medicine, Gansu Provincial Hospital, Lanzhou, Gansu, People's Republic of China
| | - Qi Wang
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, People's Republic of China.
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Akutko K, Stawarski A. Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases. J Clin Med 2021; 10:2466. [PMID: 34199428 PMCID: PMC8199601 DOI: 10.3390/jcm10112466] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/17/2021] [Accepted: 05/31/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children.
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Affiliation(s)
- Katarzyna Akutko
- 2nd Department and Clinic of Paediatrics, Gastroenterology and Nutrition, Medical University of Wroclaw, M. Curie-Skłodowskiej St. 50/52, 50-369 Wrocław, Poland;
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Wei R, Chen X, Hu L, He Z, Ouyang X, Liang S, Dai S, Sha W, Chen C. Dysbiosis of intestinal microbiota in critically ill patients and risk of in-hospital mortality. Am J Transl Res 2021; 13:1548-1557. [PMID: 33841678 PMCID: PMC8014420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 12/08/2020] [Indexed: 06/12/2023]
Abstract
BACKGROUND Despite the essential functions of the intestinal microbiota in human physiology, little research was reported on gut microbiota alterations in intensive care patients. This investigation examined the dysbacteriosis of intestinal flora in critically ill patients and evaluated the prognostic performance of this dysbiosis to predict in-hospital mortality. METHODS A prospective cohort of patients were consecutively recruited in the Intensive Care Units (ICUs) in Guangdong Provincial People's Hospital from March 2017 through October 2017. Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were assessed, and fecal samples were taken for examination within 24 hours of ICU admission. The taxonomic composition of the intestinal microbiome was determined using 16S rDNA gene sequencing. Patients were divided into survival and death groups based on hospital outcomes. The two groups were statistically compared using the Wilcoxon test and Metastats analysis. The genera of bacteria showing significantly different abundance between groups were assessed as predictors of in-hospital death. The prognostic value of bacterial abundance alone and in combination with APACHE II or SOFA score was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS Among the 61 patients examined, 12 patients (19.7%) died during their hospital stay. Bifidobacterium abundance was higher in the survival group than the death group (P = 0.031). The AUROC of Bifidobacterium abundance in identifying in-hospital death at a cut-off probability of 0.0041 was 0.718 (95% confidence interval [CI], 0.588-0.826). The panel of Bifidobacterium abundance plus SOFA (AUROC, 0.882; 95% CI, 0.774-0.950) outperformed SOFA (AUROC, 0.649; 95% CI, 0.516-0.767; P = 0.012) and Bifidobacterium abundance alone (P = 0.007). The panel of Bifidobacterium abundance plus APACHE II (AUROC, 0.876; 95% CI, 0.766-0.946) outperformed APACHE II (AUROC, 0.724; 95% CI, 0.595-0.831; P = 0.035) and Bifidobacterium abundance alone (P = 0.012). CONCLUSIONS Dysbiosis of intestinal microbiota with variable degrees of reduction in Bifidobacterium abundance exhibited promising performance in the predicting of in-hospital mortality and provides incremental prognostic value to existing scoring systems in the adult intensive care unit (ICU) setting.
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Affiliation(s)
- Ru Wei
- Department of Child Health Care, Guangzhou Women and Children’s Medical CenterNo. 9 Jinsui Road, Guangzhou 510623, Guangdong Province, China
| | - Xu Chen
- The Second School of Clinical Medicine, Southern Medical UniversityGuangzhou 510515, Guangdong, China
| | - Linhui Hu
- Department of Critical Care Medicine, Maoming People’s Hospital101 Weimin Road, Maoming 525000, Guangdong, China
| | - Zhimei He
- Guangdong Provincial People’s Hospital, School of Medicine, South China University of TechnologyGuangzhou 510080, Guangdong, China
| | - Xin Ouyang
- Guangdong Provincial People’s Hospital, School of Medicine, South China University of TechnologyGuangzhou 510080, Guangdong, China
| | - Silin Liang
- Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Shixue Dai
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, South China University of Technology106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, South China University of Technology106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Chunbo Chen
- Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
- Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences96 Dongchuan Road, Guangzhou 510080, Guangdong, China
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Al-Hadidi A, Navarro J, Goodman SD, Bailey MT, Besner GE. Lactobacillus reuteri in Its Biofilm State Improves Protection from Experimental Necrotizing Enterocolitis. Nutrients 2021; 13:nu13030918. [PMID: 33809097 PMCID: PMC8000340 DOI: 10.3390/nu13030918] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/11/2022] Open
Abstract
Necrotizing enterocolitis (NEC) is a devastating disease predominately found in premature infants that is associated with significant morbidity and mortality. Despite decades of research, medical management with broad spectrum antibiotics and bowel rest has remained relatively unchanged, with no significant improvement in patient outcomes. The etiology of NEC is multi-factorial; however, gastrointestinal dysbiosis plays a prominent role in a neonate's vulnerability to and development of NEC. Probiotics have recently emerged as a new avenue for NEC therapy. However, current delivery methods are associated with potential limitations, including the need for at least daily administration in order to obtain any improvement in outcomes. We present a novel formulation of enterally delivered probiotics that addresses the current limitations. A single enteral dose of Lactobacillus reuteri delivered in a biofilm formulation increases probiotic survival in acidic gastric conditions, increases probiotic adherence to gastrointestinal epithelial cells, and reduces the incidence, severity, and neurocognitive sequelae of NEC in experimental models.
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Affiliation(s)
- Ameer Al-Hadidi
- Department of Pediatric Surgery, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA;
| | - Jason Navarro
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA; (J.N.); (S.D.G.); (M.T.B.)
| | - Steven D. Goodman
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA; (J.N.); (S.D.G.); (M.T.B.)
| | - Michael T. Bailey
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA; (J.N.); (S.D.G.); (M.T.B.)
| | - Gail E. Besner
- Department of Pediatric Surgery, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA;
- Correspondence: ; Tel.: +1-614-722-3914
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Identification of New Potential Biotherapeutics from Human Gut Microbiota-Derived Bacteria. Microorganisms 2021; 9:microorganisms9030565. [PMID: 33803291 PMCID: PMC7998412 DOI: 10.3390/microorganisms9030565] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/26/2021] [Accepted: 03/03/2021] [Indexed: 02/07/2023] Open
Abstract
The role of the gut microbiota in health and disease is well recognized and the microbiota dysbiosis observed in many chronic diseases became a new therapeutic target. The challenge is to get a better insight into the functionality of commensal bacteria and to use this knowledge to select live biotherapeutics as new preventive or therapeutic products. In this study, we set up a screening approach to evaluate the functional capacities of a set of 21 strains isolated from the gut microbiota of neonates and adults. For this purpose, we selected key biological processes involved in the microbiome-host symbiosis and known to impact the host physiology i.e., the production of short-chain fatty acids and the ability to strengthen an epithelial barrier (Caco-2), to induce the release of the anti-inflammatory IL-10 cytokine after co-culture with human immune cells (PBMC) or to increase GLP-1 production from STC-1 endocrine cell line. This strategy highlighted fifteen strains exhibiting beneficial activities among which seven strains combined several of them. Interestingly, this work revealed for the first time a high prevalence of potential health-promoting functions among intestinal commensal strains and identified several appealing novel candidates for the management of chronic diseases, notably obesity and inflammatory bowel diseases.
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Metagenomic analysis of the gut microbiome composition associated with vitamin D supplementation in Taiwanese infants. Sci Rep 2021; 11:2856. [PMID: 33536562 PMCID: PMC7859236 DOI: 10.1038/s41598-021-82584-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 01/18/2021] [Indexed: 02/07/2023] Open
Abstract
Early childhood is a critical stage for the foundation and development of the gut microbiome, large amounts of essential nutrients are required such as vitamin D. Vitamin D plays an important role in regulating calcium homeostasis, and deficiency can impair bone mineralization. In addition, most people know that breastfeeding is advocated to be the best thing for a newborn; however, exclusively breastfeeding infants are not easily able to absorb an adequate amount of vitamin D from breast milk. Understanding the effects of vitamin D supplementation on gut microbiome can improve the knowledge of infant health and development. A total of 62 fecal sample from healthy infants were collected in Taiwan. Of the 62 infants, 31 were exclusively breastfed infants and 31 were mixed- or formula-fed infants. For each feeding type, one subgroup of infants received 400 IU of vitamin D per day, and the remaining infants received a placebo. In total, there are 15 breastfed and 20 formula-fed infants with additional vitamin D supplementation, and 16 breastfed and 11 formula-fed infants belong to control group, respectively. We performed a comparative metagenomic analysis to investigate the distribution and diversity of infant gut microbiota among different types of feeding regimes with and without vitamin D supplementation. Our results reveal that the characteristics of infant gut microbiota not only depend on the feeding types but also on nutrients intake, and demonstrated that the vitamin D plays an important role in modulating the infant gut microbiota, especially increase the proportion of probiotics in breast-fed infants.
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Carbone EA, D'Amato P, Vicchio G, De Fazio P, Segura-Garcia C. A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders. Eur Psychiatry 2020; 64:e2. [PMID: 33416044 PMCID: PMC8057489 DOI: 10.1192/j.eurpsy.2020.109] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs. Methods This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs. Results Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation. Conclusions Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut–brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.
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Affiliation(s)
- Elvira Anna Carbone
- Department of Health Sciences, University "Magna Graecia", Catanzaro88100, Italy.,Outpatient Service for Clinical Research and Treatment of Eating Disorders, University Hospital Mater Domini, Catanzaro88100, Italy
| | - Pasquale D'Amato
- Department of Medical and Surgical Sciences, University "Magna Graecia", Catanzaro88100, Italy
| | - Giuseppe Vicchio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende87036, Italy
| | - Pasquale De Fazio
- Department of Health Sciences, University "Magna Graecia", Catanzaro88100, Italy
| | - Cristina Segura-Garcia
- Outpatient Service for Clinical Research and Treatment of Eating Disorders, University Hospital Mater Domini, Catanzaro88100, Italy.,Department of Medical and Surgical Sciences, University "Magna Graecia", Catanzaro88100, Italy
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Quinn WJ, Jiao J, TeSlaa T, Stadanlick J, Wang Z, Wang L, Akimova T, Angelin A, Schäfer PM, Cully MD, Perry C, Kopinski PK, Guo L, Blair IA, Ghanem LR, Leibowitz MS, Hancock WW, Moon EK, Levine MH, Eruslanov EB, Wallace DC, Baur JA, Beier UH. Lactate Limits T Cell Proliferation via the NAD(H) Redox State. Cell Rep 2020; 33:108500. [PMID: 33326785 PMCID: PMC7830708 DOI: 10.1016/j.celrep.2020.108500] [Citation(s) in RCA: 190] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 10/08/2020] [Accepted: 11/18/2020] [Indexed: 12/01/2022] Open
Abstract
Immune cell function is influenced by metabolic conditions. Low-glucose, high-lactate environments, such as the placenta, gastrointestinal tract, and the tumor microenvironment, are immunosuppressive, especially for glycolysis-dependent effector T cells. We report that nicotinamide adenine dinucleotide (NAD+), which is reduced to NADH by lactate dehydrogenase in lactate-rich conditions, is a key point of metabolic control in T cells. Reduced NADH is not available for NAD+-dependent enzymatic reactions involving glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate dehydrogenase (PGDH). We show that increased lactate leads to a block at GAPDH and PGDH, leading to the depletion of post-GAPDH glycolytic intermediates, as well as the 3-phosphoglycerate derivative serine that is known to be important for T cell proliferation. Supplementing serine rescues the ability of T cells to proliferate in the presence of lactate-induced reductive stress. Directly targeting the redox state may be a useful approach for developing novel immunotherapies in cancer and therapeutic immunosuppression. Quinn et al. report that lactate has an acidity-independent suppressive effect on effector T cell proliferation mediated through a shift from NAD+ to NADH (lactate-induced reductive stress). This impairs glycolysis and glucose-derived serine production, which is required for effector T cell proliferation.
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Affiliation(s)
- William J Quinn
- Department of Physiology and Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Jing Jiao
- Division of Nephrology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Tara TeSlaa
- Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA
| | - Jason Stadanlick
- Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Zhonglin Wang
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Liqing Wang
- Division of Transplant Immunology, Department of Pathology and Laboratory Medicine and Biesecker Center for Pediatric Liver Disease, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Tatiana Akimova
- Division of Transplant Immunology, Department of Pathology and Laboratory Medicine and Biesecker Center for Pediatric Liver Disease, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Alessia Angelin
- Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Patrick M Schäfer
- Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Michelle D Cully
- Division of Nephrology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Caroline Perry
- Department of Physiology and Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Piotr K Kopinski
- Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Lili Guo
- Penn SRP Center, Center of Excellence in Environmental Toxicology and Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Ian A Blair
- Penn SRP Center, Center of Excellence in Environmental Toxicology and Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Louis R Ghanem
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Michael S Leibowitz
- Division of Oncology, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Wayne W Hancock
- Division of Transplant Immunology, Department of Pathology and Laboratory Medicine and Biesecker Center for Pediatric Liver Disease, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Edmund K Moon
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Matthew H Levine
- Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Evgeniy B Eruslanov
- Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Douglas C Wallace
- Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Joseph A Baur
- Department of Physiology and Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Ulf H Beier
- Division of Nephrology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA.
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Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives. J Clin Med 2020; 9:jcm9113535. [PMID: 33139601 PMCID: PMC7692447 DOI: 10.3390/jcm9113535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/28/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.
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Dose-Dependent Effects of Dietary Xylooligosaccharides Supplementation on Microbiota, Fermentation and Metabolism in Healthy Adult Cats. Molecules 2020; 25:molecules25215030. [PMID: 33138291 PMCID: PMC7662210 DOI: 10.3390/molecules25215030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 10/27/2020] [Accepted: 10/27/2020] [Indexed: 12/30/2022] Open
Abstract
In order to investigate the effect and appropriate dose of prebiotics, this study evaluated the effect of two levels of xylooligosaccharides (XOS) in cats. Twenty-four healthy adult cats were divided into three groups: no-XOS control diet with 1% cellulose; low XOS supplementation (LXOS) with 0.04% XOS and 0.96% cellulose; and high XOS supplementation (HXOS) with 0.40% XOS and 0.60% cellulose. Both XOS groups increased blood 3-hydroxybutyryl carnitine levels and decreased hexadecanedioyl carnitine levels. Both XOS treatments displayed an increased bacterial abundance of Blautia, Clostridium XI, and Collinsella and a decreased abundance of Megasphaera and Bifidobacterium. LXOS groups increased fecal pH and bacterial abundance of Streptococcus and Lactobacillus, decreased blood glutaryl carnitine concentration, and Catenibacterium abundance. HXOS group showed a more distinct microbiome profile and higher species richness, and an increased bacterial abundance of Subdoligranulum, Ruminococcaceae genus (unassigned genus), Erysipelotrichaceae genus, and Lachnospiraceae. Correlations between bacterial abundances and blood and fecal parameters were also observed. In conclusion, XOS could benefit feline gut health by altering microbiota; its effects dependant on the dose. The higher-dose XOS increased bacterial populations that possibly promoted intestinal fermentation, while the lower dose altered populations of carbohydrate-metabolic microbiota and possibly modulated host metabolism. Low-dose prebiotics may become a trend in future studies.
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Zhao N, Liu JM, Yang FE, Ji XM, Li CY, Lv SW, Wang S. A Novel Mediation Strategy of DSS-Induced Colitis in Mice Based on an Iron-Enriched Probiotic and In Vivo Bioluminescence Tracing. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:12028-12038. [PMID: 33052690 DOI: 10.1021/acs.jafc.0c05260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Iron deficiency (ID) caused by blood loss and/or reduced iron absorption is a serious problem influencing health in inflammatory bowel disease (IBD). However, traditional iron supplements may fail to meet no side effect demands for ID of IBD; thus, a new iron supplementation is highly desired to be developed. Herein, for the first time, probiotic Lactobacillus alimentarius NKU556 with an iron-enriching ability was screened from Chinese traditional fermented food then employed to intervene DSS-induced colitis with bioluminescence tracing in mice. As expected, oral administration with NKU556-Fe can remarkably enhance the expression of tight junction proteins and effectively reduce the pro-inflammatory cytokines as well as the oxidative stress on DSS-induced colitis in mice. Meanwhile, in comparison with the FeSO4 group, the intake of NKU556-Fe could suppress the expression of hepcidin derived from the liver and reduce the degradation of FPN1, thereby leading to the increase in the iron absorption of colitis in mice. According to the bioluminescence result, it was believed that the beneficial effects of oral administration with NKU556/NKU556-Fe on DSS-induced colitis in mice were hardly related to its metabolites but associated with its own function. These results concluded that the oral administration of NKU556-Fe could relieve colitis inflammation and increase iron absorption. In summary, current work not only proposed a novel mediation strategy for IBD but also offered some inspirations for future treatment of extraintestinal complications.
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Affiliation(s)
- Ning Zhao
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Jing-Min Liu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Fei-Er Yang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Xue-Meng Ji
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Chun-Yang Li
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Shi-Wen Lv
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
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Cuffaro B, Assohoun ALW, Boutillier D, Súkeníková L, Desramaut J, Boudebbouze S, Salomé-Desnoulez S, Hrdý J, Waligora-Dupriet AJ, Maguin E, Grangette C. In Vitro Characterization of Gut Microbiota-Derived Commensal Strains: Selection of Parabacteroides distasonis Strains Alleviating TNBS-Induced Colitis in Mice. Cells 2020; 9:cells9092104. [PMID: 32947881 PMCID: PMC7565435 DOI: 10.3390/cells9092104] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 07/15/2020] [Accepted: 07/20/2020] [Indexed: 12/17/2022] Open
Abstract
Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.
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Affiliation(s)
- Bernardo Cuffaro
- Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Centre d’Infection et d’Immunité de Lille, 59000 Lille, France; (B.C.); (D.B.); (J.D.)
- Institut Micalis, MIHA Team, Université Paris-Saclay, INRAE, AgroParisTech, 78350 Jouy-en-Josas, France; (A.L.W.A.); (S.B.)
| | - Aka L. W. Assohoun
- Institut Micalis, MIHA Team, Université Paris-Saclay, INRAE, AgroParisTech, 78350 Jouy-en-Josas, France; (A.L.W.A.); (S.B.)
- Laboratoire de Biotechnologie et Microbiologie des Aliments, UFR en Sciences et Technologies des Aliments, Université Nangui Abrogoua, Abidjan 00225, Côte d’Ivoire
| | - Denise Boutillier
- Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Centre d’Infection et d’Immunité de Lille, 59000 Lille, France; (B.C.); (D.B.); (J.D.)
| | - Lenka Súkeníková
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital, 121 08 Prague, Czech Republic; (L.S.); (J.H.)
| | - Jérémy Desramaut
- Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Centre d’Infection et d’Immunité de Lille, 59000 Lille, France; (B.C.); (D.B.); (J.D.)
| | - Samira Boudebbouze
- Institut Micalis, MIHA Team, Université Paris-Saclay, INRAE, AgroParisTech, 78350 Jouy-en-Josas, France; (A.L.W.A.); (S.B.)
| | - Sophie Salomé-Desnoulez
- Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41-UMS 2014-PLBS, 59000 Lille, France;
| | - Jiří Hrdý
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital, 121 08 Prague, Czech Republic; (L.S.); (J.H.)
| | | | - Emmanuelle Maguin
- Institut Micalis, MIHA Team, Université Paris-Saclay, INRAE, AgroParisTech, 78350 Jouy-en-Josas, France; (A.L.W.A.); (S.B.)
- Correspondence: (E.M.); (C.G.); Tel.: +33-681-151-925 (E.M.); +33-320-877-392 (C.G.)
| | - Corinne Grangette
- Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Centre d’Infection et d’Immunité de Lille, 59000 Lille, France; (B.C.); (D.B.); (J.D.)
- Correspondence: (E.M.); (C.G.); Tel.: +33-681-151-925 (E.M.); +33-320-877-392 (C.G.)
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Axelrod CL, Brennan CJ, Cresci G, Paul D, Hull M, Fealy CE, Kirwan JP. UCC118 supplementation reduces exercise-induced gastrointestinal permeability and remodels the gut microbiome in healthy humans. Physiol Rep 2020; 7:e14276. [PMID: 31758610 PMCID: PMC6874782 DOI: 10.14814/phy2.14276] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 10/04/2019] [Accepted: 10/05/2019] [Indexed: 01/25/2023] Open
Abstract
Dysregulation of gut microbiota and intestinal barrier function has emerged as potential mechanisms underlying digestive diseases, yet targeted therapies are lacking The purpose of this investigation was to assess the efficacy of UCC118, a characterized probiotic strain, on exercise‐induced GI permeability in healthy humans. In a randomized, double‐blind, placebo‐controlled crossover study, seven healthy adults received 4 weeks of daily UCC118 or placebo supplementation. GI hyperpermeability was induced by strenuous treadmill running performed before and after each supplementation period. While running, participants ingested 5 g of lactulose, rhamnose, and sucrose. Urine was collected before, immediately after, and every hour for 5 h after exercise to assess GI permeability. Metagenomic sequencing was performed on fecal homogenates collected prior to exercise to identify changes in microbial diversity and taxon abundances. Inflammatory biomarkers were assessed from blood and fecal homogenates collected prior to and immediately following the cessation of exercise. Exercise significantly induced intestinal permeability of lactulose, rhamnose, and sucrose (P < 0.001). UCC118 significantly reduced sucrose (Δ = −0.38 ± 0.13 vs. 1.69 ± 0.79; P < 0.05) recovery, with no substantial change in lactulose (Δ = −0.07 ± 0.23 vs. 0.35 ± 0.15; P = 0.16) or rhamnose (Δ = −0.06 ± 0.22 vs. 0.48 ± 0.28; P = 0.22). Taxonomic sequencing revealed 99 differentially regulated bacteria spanning 6 taxonomic ranks (P < 0.05) after UCC118 supplementation. No differences in plasma IL‐6 or fecal zonulin were observed after UCC118 supplementation. The results described herein provide proof of principle that 4 weeks of UCC118 supplementation attenuated exercise‐induced intestinal hyperpermeability. Further research is warranted to investigate the as‐yet‐to‐be defined molecular processes of intestinal hyperpermeability and the effects of probiotic supplementation. Dysregulation of gut microbiota and intestinal barrier function have emerged as potential mechanisms underlying digestive diseases, yet targeted therapies are lacking. In a randomized, double‐blind, placebo‐controlled crossover study, 7 healthy adults 30 received 4 weeks of daily UCC118 or placebo supplementation. UCC118 significantly reduced sucrose recovery. Taxonomic sequencing revealed 99 differentially regulated gut microbes by UCC118. The results herein provide proof of principle that UCC118 supplementation can reduce intestinal hyperpermeability.![]()
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Affiliation(s)
- Christopher L Axelrod
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.,Integrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, Los Angeles.,Department of Translational Services, Pennington Biomedical Research Center, Baton Rouge, Los Angeles
| | - Connery J Brennan
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Gail Cresci
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Deborah Paul
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Michaela Hull
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Ciarán E Fealy
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - John P Kirwan
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.,Integrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, Los Angeles
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45
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Yue B, Yu ZL, Lv C, Geng XL, Wang ZT, Dou W. Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease. World J Gastroenterol 2020; 26:4378-4393. [PMID: 32874052 PMCID: PMC7438192 DOI: 10.3748/wjg.v26.i30.4378] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/02/2020] [Accepted: 07/04/2020] [Indexed: 02/06/2023] Open
Abstract
The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.
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Affiliation(s)
- Bei Yue
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhi-Lun Yu
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Cheng Lv
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiao-Long Geng
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zheng-Tao Wang
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wei Dou
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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46
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Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis? Cancers (Basel) 2020; 12:cancers12082272. [PMID: 32823729 PMCID: PMC7465663 DOI: 10.3390/cancers12082272] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 08/06/2020] [Accepted: 08/10/2020] [Indexed: 12/18/2022] Open
Abstract
Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
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Alizadeh S, Esmaeili A, Omidi Y. Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2020; 23:886-893. [PMID: 32774810 PMCID: PMC7395184 DOI: 10.22038/ijbms.2020.43016.10115] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Objectives Chemotherapies used to treat colon cancer might often fail due to the emergence of chemoresistance and side effects. Escherichia coli Nissle 1917 (EcN) is a beneficial probiotic, whose molecular mechanisms in the prevention of colon cancer are yet to be fully understood. The present study assessed the anti-cancer effects of EcN treatments in human colorectal cancer, HT-29 cell line, with the analysis of related mechanisms. Materials and Methods The co-culture conditioned-media (CM) of EcN with adenocarcinoma HT-29 cells and heat-inactivated bacteria (HIB) were applied for the treatment of the HT-29 cells. To study the inhibition potential of CM and HIB on cancer cells, various cellular/molecular analyses were implemented, including DAPI-staining and DNA ladder assays, flow cytometry and Real-time quantitative PCR (qPCR), as well as Western blotting analyses. Results Our results indicated that EcN could elicit apoptotic impacts on the colon cancer HT-29 cells by up-regulating PTEN and Bax and down-regulating AKT1 and Bcl-xL genes. Conclusion Based on our findings, EcN is proposed as a useful supplemental probiotic treatment against colon cancer.
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Affiliation(s)
- Siamak Alizadeh
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.,Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolghasem Esmaeili
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Yadollah Omidi
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
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Leccese G, Bibi A, Mazza S, Facciotti F, Caprioli F, Landini P, Paroni M. Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn's Disease. Cells 2020; 9:cells9081824. [PMID: 32752244 PMCID: PMC7464949 DOI: 10.3390/cells9081824] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/21/2020] [Accepted: 07/31/2020] [Indexed: 02/07/2023] Open
Abstract
Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel diseases (IBD). In this work, we studied how Lactobacillus and Bifidobacterium strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6–CCL20 and IL-23/Th17 axes in Crohn’s disease (CD) and ulcerative colitis (UC) patients. All Lactobacillus and Bifidobacterium strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6–CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only B. breve Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-α and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients.
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Affiliation(s)
- Gabriella Leccese
- Department of Biosciences, Università degli Studi di Milano, 20133 Milan, Italy; (G.L.); (A.B.); (P.L.)
| | - Alessia Bibi
- Department of Biosciences, Università degli Studi di Milano, 20133 Milan, Italy; (G.L.); (A.B.); (P.L.)
| | - Stefano Mazza
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy; (S.M.); (F.C.)
| | - Federica Facciotti
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, 20139 Milan, Italy;
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy; (S.M.); (F.C.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20135 Milan, Italy
| | - Paolo Landini
- Department of Biosciences, Università degli Studi di Milano, 20133 Milan, Italy; (G.L.); (A.B.); (P.L.)
| | - Moira Paroni
- Department of Biosciences, Università degli Studi di Milano, 20133 Milan, Italy; (G.L.); (A.B.); (P.L.)
- Correspondence:
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Al Azzaz J, Al Tarraf A, Heumann A, Da Silva Barreira D, Laurent J, Assifaoui A, Rieu A, Guzzo J, Lapaquette P. Resveratrol Favors Adhesion and Biofilm Formation of Lacticaseibacillus paracasei subsp. paracasei Strain ATCC334. Int J Mol Sci 2020; 21:ijms21155423. [PMID: 32751457 PMCID: PMC7432909 DOI: 10.3390/ijms21155423] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 07/21/2020] [Accepted: 07/28/2020] [Indexed: 12/21/2022] Open
Abstract
Bacterial strains of the Lactobacillaceae family are widely used as probiotics for their multifaceted potential beneficial properties. However, no official recommendations for their clinical use exist since, in many cases, oral administrations of these bacteria displayed limited beneficial effects in human. Additional research is thus needed to improve the efficiency of existing strains with strong potential. In this context, we assess in vitro the effects of nine polyphenols to stimulate biofilm formation by lactobacilli, a feature enhancing their functionalities. Among these polyphenols, we identify trans-Resveratrol (referred to hereafter as Resveratrol) as a potent inducer of biofilm formation by Lacticaseibacillus paracasei (formerly designated as Lactobacillus paracasei) ATCC334 strain. This effect is strain-dependent and relies on the enhancement of L. paracasei adhesion to abiotic and biotic surfaces, including intestinal epithelial cells. Mechanistically, Resveratrol modify physico-chemical properties of the bacterial surface and thereby enhances L. paracasei aggregation, subsequently facilitating adhesion and biofilm development. Together, our in vitro data demonstrate that Resveratrol might be used to modulate the behavior of Lactobacilli with probiotic properties. Combination of probiotics and polyphenols could be considered to enhance the probiotic functionalities in further in vivo studies.
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Affiliation(s)
- Jana Al Azzaz
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
- Muséum National d’Histoire Naturelle (MNHN), Centre National de la Recherche Scientifique, UMR7245, Molécules de Communication et Adaptation des Microorganismes (MCAM), 75005 Paris, France
| | - Alissar Al Tarraf
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
| | - Arnaud Heumann
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
| | - David Da Silva Barreira
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
| | - Julie Laurent
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
| | - Ali Assifaoui
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
| | - Aurélie Rieu
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
| | - Jean Guzzo
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
- Correspondence: (J.G.); (P.L.)
| | - Pierre Lapaquette
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, F-21000 Dijon, France; (J.A.A.); (A.A.T.); (A.H.); (D.D.S.B.); (J.L.); (A.A.); (A.R.)
- Correspondence: (J.G.); (P.L.)
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50
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Tun HM, Li S, Yoon I, Meale SJ, Azevedo PA, Khafipour E, Plaizier JC. Saccharomyces cerevisiae fermentation products (SCFP) stabilize the ruminal microbiota of lactating dairy cows during periods of a depressed rumen pH. BMC Vet Res 2020; 16:237. [PMID: 32653000 PMCID: PMC7353776 DOI: 10.1186/s12917-020-02437-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 06/18/2020] [Indexed: 11/22/2022] Open
Abstract
Background Effects of Saccharomyces cerevisiae fermentation products (SCFP) on rumen microbiota were determined in vitro and in vivo under a high and a depressed pH. The in vitro trial determined the effects of Original XPC and NutriTek (Diamond V, Cedar Rapids, IA) at doses of 1.67 and 2.33 g/L, respectively, on the abundances of rumen bacteria under a high pH (> 6.3) and a depressed pH (5.8–6.0) using quantitative PCR (qPCR). In the in vivo trial eight rumen-cannulated lactating dairy cows were used in a cross-over design. Cows were randomly assigned to SCFP treatments (Original XPC, Diamond V, Cedar Rapids, IA) or control (No SCFP) before two 5-week experimental periods. During the second period, SCFP treatments were reversed. Cows on the SCFP treatment were supplemented with 14 g/d of SCFP and 126 g/d of ground corn. Other cows received 140 g/d ground corn. During the first 4 wk. of each period, cows received a basal diet containing 153 g/kg of starch. During week 5 of both periods, the rumen pH was depressed by a SARA challenge. This included replacing 208 g/kg of the basal diet with pellets of ground wheat and barley, resulting in a diet that contained 222 g/kg DM of starch. Microbial communities in rumen liquid digesta were examined by pyrosequencing, qPCR, and shotgun metagenomics. Results During the in vitro experiment, XPC and NutriTek increased the relative abundances of Ruminococcus flavefaciens, and Fibrobacter succinogenes determined at both the high and the depressed pH, with NutriTek having the largest effect. The relative abundances of Prevotella brevis, R. flavefaciens, ciliate protozoa, and Bifidobacterium spp. were increased by XPC in vivo. Adverse impacts of the in vivo SARA challenge included reductions of the richness and diversity of the rumen microbial community, the abundances of Bacteroidetes and ciliate protozoa in the rumen as determined by pyrosequencing, and the predicted functionality of rumen microbiota as determined by shotgun metagenomics. These reductions were attenuated by XPC supplementation. Conclusions The negative effects of grain-based SARA challenges on the composition and predicted functionality of rumen microbiota are attenuated by supplementation with SCFP.
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Affiliation(s)
- Hein M Tun
- Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada.,Present address: HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Shucong Li
- Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada
| | | | - Sarah J Meale
- School of Agriculture and Food Science, University of Queensland Gatton campus, Gatton, Australia
| | - Paula A Azevedo
- Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada
| | - Ehsan Khafipour
- Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada. .,Present Address: Diamond V, Cedar Rapids, IA, USA.
| | - Jan C Plaizier
- Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada.
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