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Träger C, Kaiser M, Freudenstein D, Heckscher S, Dettmer K, Oefner PJ, Liebisch G, Hiergeist A, Gessner A, Lee DH, Angstwurm K, Linker RA, Haase S. A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals. EBioMedicine 2025; 116:105743. [PMID: 40359627 DOI: 10.1016/j.ebiom.2025.105743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 04/18/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Modulation of the gut microbiota composition has been suggested as a potential disease modifying therapy in immune-mediated diseases such as multiple sclerosis (MS). However, a conclusive mechanism linking gut microbiota modulation to peripheral immune responses has remained elusive so far. METHODS In this exploratory cohort study, people with MS (pwMS) and healthy controls (HC) supplemented a lactobacilli-rich probiotic for two or six weeks and were additionally investigated six weeks after the last intake. Immune cell phenotyping was performed in blood samples, complemented by mRNA expression analysis, serum cytokine measurements, and Treg suppression assays. Besides gut microbiota composition analysis, metabolite production was investigated in stool and serum. Links between metabolites and peripheral immune system were investigated in in vitro T cell differentiation assays. FINDINGS In peripheral blood, Treg cells increased in both groups, while Th1 cells were significantly reduced in pwMS. This promotion of a regulatory immunophenotype was complemented by increased concentrations of IL-10 in serum and higher expression of IL10 and CTLA4. Functional assays revealed an enhanced suppressive capacity of Treg cells due to the probiotic intervention. The tryptophan metabolite indole-3-acetate (IAA) increased in stool and serum samples of pwMS during the probiotic intake. In vitro, IAA specifically enhanced the formation of IL-10 secreting T cells together with CYP1a1 expression. This effect was blocked by addition of an aryl hydrocarbon receptor (AHR) inhibitor. INTERPRETATION A lactobacilli-enriched probiotic promotes a regulatory immunophenotype in pwMS, probably by enhancing AHR agonists in the gut. It may be of interest as add-on therapy in immune-mediated diseases such as MS. FUNDING This study has in part been funded by Novartis Pharma GmbH and BMBF grant no. 01EJ2202B.
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Affiliation(s)
- Constantin Träger
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Maria Kaiser
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - David Freudenstein
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Simon Heckscher
- Institute of Functional Genomics, University of Regensburg, Regensburg, Germany
| | - Katja Dettmer
- Institute of Functional Genomics, University of Regensburg, Regensburg, Germany
| | - Peter J Oefner
- Institute of Functional Genomics, University of Regensburg, Regensburg, Germany
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany
| | - Andreas Hiergeist
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Germany
| | - André Gessner
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Germany
| | - De-Hyung Lee
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Klemens Angstwurm
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Ralf A Linker
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Stefanie Haase
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany.
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Zangeneh Z, Rostamian M, Motamedi H, Alvandi A, Abiri R. The potential effectiveness of probiotics in reducing multiple sclerosis progression in preclinical and clinical studies: A worldwide systematic review and meta-analysis. PLoS One 2025; 20:e0319755. [PMID: 40273120 PMCID: PMC12021188 DOI: 10.1371/journal.pone.0319755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 02/06/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND AND OBJECTIVE Multiple Sclerosis (MS) is an immune-mediated disease characterized by nerve cell inflammation and demyelination. The effectiveness of probiotics in reducing inflammatory damage in MS. Therefore, the aim of this systematic review and meta-analysis was the potential effectiveness of probiotics in reducing Multiple Sclerosis progression in preclinical and clinical studies. METHODS PubMed, Scopus, Cochrane, and Google Scholar databases were searched using multiple relevant keywords, and screening was carried out based on the inclusion/exclusion criteria from January 2004 to August 16, 2024. RESULTS Based on our criteria, 269 papers were obtained, and after omission of unsuitable articles, 23 full-text articles consisting of 17 animal studies and six human models were selected. It was concluded that in an experimental autoimmune encephalomyelitis (EAE) animal model, probiotics such as Bifidobacterium, Prevotella, and Lactobacillus can decrease the T helper 1 (Th1)/Th17 ratio while inducing interferon gamma (IFN-γ) and interleukin (IL)-17 levels. In all cases, probiotics can modulate immune cells and cytokines and consequently decrease EAE signs and symptoms. In all human studies, single or multiple probiotics decreased the severity of disease and changed the gut microbiota population. CONCLUSION Our results showed that probiotics can control the development of MS by reducing inflammatory conditions, and may have beneficial effects in the prevention and treatment of MS.
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Affiliation(s)
- Zahra Zangeneh
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mosayeb Rostamian
- Infectious Diseases Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Amirhooshang Alvandi
- Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ramin Abiri
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Hajjeh O, Rajab I, Bdair M, Saife S, Zahran A, Nazzal I, AbuZahra MI, Jallad H, Abukhalil MM, Hallak M, Al-Said OS, Al-Braik R, Sawaftah Z, Milhem F, Almur O, Saife S, Aburemaileh M, Abuhilal A. Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease. Neuroscience 2025; 572:232-247. [PMID: 40088964 DOI: 10.1016/j.neuroscience.2025.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/17/2025]
Abstract
The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.
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Affiliation(s)
- Orabi Hajjeh
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Islam Rajab
- Internal Medicine Department, St. Joseph's University Medical Center, 703 Main St, Paterson, NJ 07503, USA
| | - Mohammad Bdair
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Sarah Saife
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Anwar Zahran
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Iyad Nazzal
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mohammad Ibrahem AbuZahra
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Hammam Jallad
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
| | - Maram M Abukhalil
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mira Hallak
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Osama S Al-Said
- Department Of Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Rama Al-Braik
- Department Of Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Zaid Sawaftah
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Fathi Milhem
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Omar Almur
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Sakeena Saife
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mohammed Aburemaileh
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Anfal Abuhilal
- Neuroscience Initiative, Advanced Science Research Center, The City University of New York (CUNY) Graduate Center, New York, NY 10031, USA
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Rai AK, Yadav M, Duary RK, Shukla P. Gut Microbiota Modulation Through Dietary Approaches Targeting Better Health During Metabolic Disorders. Mol Nutr Food Res 2025:e70033. [PMID: 40195821 DOI: 10.1002/mnfr.70033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 02/26/2025] [Accepted: 03/07/2025] [Indexed: 04/09/2025]
Abstract
The impact of gut microbiota is known to play a significant role in an individual's metabolism and health. Many harmful food products or dietary imbalance adversely affect human health and changing lifestyle, environmental factors, and food habits may have their effect on gut microbiota. It has emerged that gut microbiota is regarded as an emerging metabolic organ, which is dependent on individual's diet and its composition. This review discusses the significance of lactic acid bacteria as a prominent inhabitant in the gut microbiota and the role of probiotics, prebiotics, and polyphenols to improve human health and metabolism. The role of fermented foods as an important source of probiotics and bioactive molecules is also discussed along with the role of gut microbiota in metabolic disorders like dyslipidemia, obesity, hypercholesterolemia, cancer, and hypertension. Finally, the review gives insights into the effective therapeutic prospects through gut microbiota alterations to tackle these metabolic disorders.
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Affiliation(s)
- Amit Kumar Rai
- BRIC-National Agri-Food and Biomanufacturing Institute (BRIC-NABI), SAS Nagar, Mohali, India
| | | | - Raj Kumar Duary
- Department of Dairy Science and Food Technology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, India
| | - Pratyoosh Shukla
- Enzyme Technology and Protein Bioinformatics Laboratory, School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, India
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Saeed M, Al-Khalaifah H, Al-Nasser A, Al-Surrayai T. Feeding the future: A new potential nutritional impact of Lactiplantibacillus plantarum and its promising interventions in future for poultry industry. Poult Sci 2025; 104:105130. [PMID: 40215877 PMCID: PMC12018113 DOI: 10.1016/j.psj.2025.105130] [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: 12/16/2024] [Revised: 04/01/2025] [Accepted: 04/02/2025] [Indexed: 04/27/2025] Open
Abstract
The increasing demand for sustainable and efficient chicken production has intensified the interest in functional feed additives such as probiotics. Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) is an important probiotic bacterium that has become an essential component in poultry nutrition owing to its diverse advantages. This bacterium improves gut health by regulating the intestinal microbiota, increasing food absorption, and strengthening the immune system. It also alleviates the detrimental impacts of pathogenic bacteria, thereby reducing the reliance on antibiotics and promoting antibiotic-free poultry production. Additionally, Lactobacillus plantarum enhances growth performance, feed conversion efficiency, and total flock productivity. Adding Lactobacillus plantarum to chicken feed helps the gut microbiota by encouraging good bacterial communities (e.g., Eubacterium, Faecalibacterium, Ligilactobacillus, Limosilactobacillus, Blautia and Clostridium). This leads to increased growth in chickens and helps maintain the balance of their gut flora. Lactobacillus plantarum has been extensively investigated as a potential feed additive to replace in-feed antibiotics. Published literature have revealed that a dietary additive of Lactobacillus plantarum improved the health and growth of broilers by improving the balance of bacteria and the metabolism of nutrients in the gut. This study explores the incorporation of Lactobacillus plantarum into poultry diets and its importance in sustainable and healthy poultry production. This study will encourage poultry scientists to investigate further before encapsulation. Innovations in Lactiplantibacillus plantarum, including its intestine colonization methods and novel strategies to improve its colonization, have the potential to transform the industry. Rapid development of tools and techniques (microencapsulated, nanotechnology, metagenomics, and transcriptome for L. plantarum) could help cover research and application shortages.
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Affiliation(s)
- Muhammad Saeed
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Hanan Al-Khalaifah
- Environment and Life Sciences Research Center, Kuwait Institute for Scientific Research, Safat, 13109, Kuwait.
| | - Afaf Al-Nasser
- Environment and Life Sciences Research Center, Kuwait Institute for Scientific Research, Safat, 13109, Kuwait
| | - Tahani Al-Surrayai
- Environment and Life Sciences Research Center, Kuwait Institute for Scientific Research, Safat, 13109, Kuwait
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Tamayo M, Agusti A, Molina-Mendoza GV, Rossini V, Frances-Cuesta C, Tolosa-Enguís V, Sanz Y. Bifidobacterium longum CECT 30763 improves depressive- and anxiety-like behavior in a social defeat mouse model through the immune and dopaminergic systems. Brain Behav Immun 2025; 125:35-57. [PMID: 39694341 DOI: 10.1016/j.bbi.2024.12.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 12/20/2024] Open
Abstract
Adolescence is a crucial period marked by profound changes in the brain. Exposure to psychological stressors such as bullying, abuse or maltreatment during this developmental period may increase the risk of developing depression, anxiety and comorbid cardiometabolic conditions. Chronic psychological stress is associated with behavioral changes and disruption of the hypothalamic-pituitary-adrenal axis, leading to corticosterone overproduction in rodents and changes in both the immune system and the gut microbiome. Here, we demonstrate the ability of Bifidobacterium longum CECT 30763 (B. longum) to ameliorate adolescent depressive and anxiety-like behaviors in a chronic social defeat (CSD) mouse model. The mechanisms underlying this beneficial effect are related to the ability of B. longum to attenuate the inflammation and immune cell changes induced by CSD after the initial stress exposure through the induction of T regulatory cells with enduring effects that may prevent and mitigate the adverse consequences of repeated stress exposure on mental and cardiometabolic health. B. longum administration also normalized dopamine release, metabolism and signaling at the end of the intervention, which may secondarily contribute to the reversal of behavioral changes. The anti-inflammatory effects of B. longum could also explain its cardioprotective effects, which were reflected in an amelioration of the oxidative stress-induced damage in the heart and improved lipid metabolism in the liver. Overall, our findings suggest that B. longum regulates the links between the immune and dopaminergic systems from the gut to the brain, potentially underpinning its beneficial psychobiotic and physiological effects in CSD.
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Affiliation(s)
- M Tamayo
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain; Department of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain
| | - A Agusti
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain.
| | - G V Molina-Mendoza
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain
| | - V Rossini
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain
| | - C Frances-Cuesta
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain
| | - V Tolosa-Enguís
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain
| | - Y Sanz
- Microbiome, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), 46980 Valencia, Spain
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Schumacher SM, Doyle WJ, Hill K, Ochoa-Repáraz J. Gut microbiota in multiple sclerosis and animal models. FEBS J 2025; 292:1330-1356. [PMID: 38817090 PMCID: PMC11607183 DOI: 10.1111/febs.17161] [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: 10/17/2023] [Revised: 04/15/2024] [Accepted: 05/10/2024] [Indexed: 06/01/2024]
Abstract
Multiple sclerosis (MS) is a chronic central nervous system (CNS) neurodegenerative and neuroinflammatory disease marked by a host immune reaction that targets and destroys the neuronal myelin sheath. MS and correlating animal disease models show comorbidities, including intestinal barrier disruption and alterations of the commensal microbiome. It is accepted that diet plays a crucial role in shaping the microbiota composition and overall gastrointestinal (GI) tract health, suggesting an interplay between nutrition and neuroinflammation via the gut-brain axis. Unfortunately, poor host health and diet lead to microbiota modifications that could lead to significant responses in the host, including inflammation and neurobehavioral changes. Beneficial microbial metabolites are essential for host homeostasis and inflammation control. This review will highlight the importance of the gut microbiota in the context of host inflammatory responses in MS and MS animal models. Additionally, microbial community restoration and how it affects MS and GI barrier integrity will be discussed.
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Affiliation(s)
| | | | - Kristina Hill
- Department of Biological Sciences, Boise State University, Boise, ID 83725
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Kim JH, Choi Y, Lee S, Oh MS. Probiotics as Potential Treatments for Neurodegenerative Diseases: a Review of the Evidence from in vivo to Clinical Trial. Biomol Ther (Seoul) 2025; 33:54-74. [PMID: 39676295 PMCID: PMC11704393 DOI: 10.4062/biomolther.2024.215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 12/08/2024] [Accepted: 12/09/2024] [Indexed: 12/17/2024] Open
Abstract
Neurodegenerative diseases (NDDs), characterized by the progressive deterioration of the structure and function of the nervous system, represent a significant global health challenge. Emerging research suggests that the gut microbiota plays a critical role in regulating neurodegeneration via modulation of the gut-brain axis. Probiotics, defined as live microorganisms that confer health benefits to the host, have garnered significant attention owing to their therapeutic potential in NDDs. This review examines the current research trends related to the microbiome-gut-brain axis across various NDDs, highlighting key findings and their implications. Additionally, the effects of specific probiotic strains, including Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus rhamnosus, on neurodegenerative processes were assessed, focusing on their potential therapeutic benefits. Overall, this review emphasizes the potential of probiotics as promising therapeutic agents for NDDs, underscoring the importance of further investigation into this emerging field.
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Affiliation(s)
- Jin Hee Kim
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yujin Choi
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Seungmin Lee
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Myung Sook Oh
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
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Sepehr A, Miri ST, Aghamohammad S, Rahimirad N, Milani M, Pourshafie MR, Rohani M. Health benefits, antimicrobial activities, and potential applications of probiotics: A review. Medicine (Baltimore) 2024; 103:e32412. [PMID: 39969286 PMCID: PMC11688011 DOI: 10.1097/md.0000000000032412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 12/02/2022] [Indexed: 02/20/2025] Open
Abstract
Gut microbiota and its metabolic activities can influence the physiology and pathology of the human body. It is well established that alterations in the balance of living microbiota can contribute to various health problems, such as inflammatory bowel disease and autoimmune disorders. Probiotics administered in sufficient quantities as functional food ingredients provide health benefits to hosts. They help to maintain the stability and composition of the gut microbiota and provide resistance to infection by pathogens. The most important probiotic bacteria are Lactobacillus spp. and Bifidobacteria spp., which protect the intestine through various mechanisms such as the production of organic acids and bacteriocins. Scientific and clinical research has demonstrated that probiotics play a role in modulating immune response and preventing cancer and chronic inflammatory diseases, especially in the gastrointestinal tract. This article summarizes the potential health benefits, antimicrobial activities, and purposes for which probiotics can be used as functional foods to improve human health.
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Affiliation(s)
- Amin Sepehr
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Seyedeh Tina Miri
- Department of Microbiology, Islamic Azad University Science and Research Branch, Tehran, Iran
| | | | - Nazanin Rahimirad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mahnaz Milani
- Department of Microbiology, Islamic Azad University Science and Research Branch, Tehran, Iran
| | | | - Mahdi Rohani
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
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Wang J, Hou Y, Mu L, Yang M, Ai X. Gut microbiota contributes to the intestinal and extraintestinal immune homeostasis by balancing Th17/Treg cells. Int Immunopharmacol 2024; 143:113570. [PMID: 39547012 DOI: 10.1016/j.intimp.2024.113570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 10/31/2024] [Accepted: 11/01/2024] [Indexed: 11/17/2024]
Abstract
Gut microbiota is generally considered to play an important role in host health due to its extensive immunomodulatory activities. Th17 and Treg cells are two important CD4+ T cell subsets involved in immune regulation, and their imbalance is closely tied to many immune diseases. Recently, abundant researches have highlighted the importance of gut microbiota in supporting intestinal and extraintestinal immunity through the balance of Th17 and Treg cells. Here, we presented a comprehensive review of these findings. This review first provided an overview of gut microbiota, along with Th17/Treg cell differentiation and cytokine production. Subsequently, the review summarized the regulatory effects of gut microbiota (in terms of species, components, and metabolites) on the Th17/Treg cell balance in the local intestines and extraintestinal organs, such as lung, liver, brain, kidney, and bone. Specifically, the Th17 and Treg cells that can be modulated by gut microbiota originate not only from the gut and extraintestinal organs, but also from peripheral blood and spleen. Then, the microbial therapeutics, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), were also reviewed because of their therapeutic potentials in addressing intestinal and extraintestinal diseases via the Th17/Treg axis. Finally, the review discussed the clinical applications and future study prospects of microbial therapeutics by targeting the Th17/Treg cell balance. In conclusion, this review focused on elucidating the regulatory effects of gut microbiota in balancing Th17/Treg cells to maintain intestinal and extraintestinal immune homeostasis, contributing to the further development and promotion of microbial therapeutics.
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Affiliation(s)
- Jing Wang
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Yaqin Hou
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Lifeng Mu
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Ming Yang
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China.
| | - Xiaopeng Ai
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China.
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Zhu F, Yin S, Wang Y, Zhong Y, Ji Q, Wu J. Effects of Probiotics on Neurodegenerative Disease-Related Symptoms and Systemic Inflammation: A Systematic Review. Int J Gen Med 2024; 17:5941-5958. [PMID: 39678681 PMCID: PMC11645901 DOI: 10.2147/ijgm.s499406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 12/05/2024] [Indexed: 12/17/2024] Open
Abstract
In recent years, probiotics, as a class of biologically active microorganisms, have increasingly attracted attention for their potential in treating neurodegenerative diseases (NDDs). To comprehensively assess the effects of probiotics on clinical symptoms and systemic inflammation regulation in various NDDs, this systematic review conducted a detailed search of the Cochrane Library, Embase, PubMed, and Web of Science databases, ultimately including 22 eligible randomized controlled trials (RCTs), with 4 RCTs for Alzheimer's Disease (AD), 10 RCTs for Parkinson's Disease (PD), 2 RCTs for Multiple Sclerosis (MS), and 2 RCTs for Mild Cognitive Impairment (MCI), and intervention durations ranging from 4 to 16 weeks. The comprehensive analysis indicates that probiotics help improve clinical symptoms related to NDDs, including gastrointestinal function, cognitive function, quality of life, and mental health. Additionally, probiotics generally have a positive effect on reducing systemic inflammation and enhancing antioxidant capacity in patients. In conclusion, existing evidence supports the promising potential of probiotics in treating NDDs. However, further large-scale, high-quality studies are needed to explore specific differences in efficacy among various probiotic strains, dosages, and modes of administration. Moreover, considering that lifestyle and dietary habits may modulate the effects of probiotics, these external factors should also be included in research considerations to gain a more comprehensive understanding of the mechanisms and application strategies of probiotics in NDDs treatment.
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Affiliation(s)
- Fengya Zhu
- Traditional Chinese Medicine Department, Zigong First People’s Hospital, Zigong, People’s Republic of China
| | - Shao Yin
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Yuan Wang
- Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Yue Zhong
- Traditional Chinese Medicine Department, Zigong First People’s Hospital, Zigong, People’s Republic of China
| | - Qiang Ji
- Traditional Chinese Medicine Department, Zigong First People’s Hospital, Zigong, People’s Republic of China
| | - Jie Wu
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
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12
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He G, Long H, He J, Zhu C. The Immunomodulatory Effects and Applications of Probiotic Lactiplantibacillus plantarum in Vaccine Development. Probiotics Antimicrob Proteins 2024; 16:2229-2250. [PMID: 39101975 DOI: 10.1007/s12602-024-10338-9] [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] [Accepted: 07/26/2024] [Indexed: 08/06/2024]
Abstract
Lactiplantibacillus plantarum (previously known as Lactobacillus plantarum) is a lactic acid bacterium that exists in various niches. L. plantarum is a food-grade microorganism that is commonly considered a safe and beneficial microorganism. It is widely used in food fermentation, agricultural enhancement, and environmental protection. L. plantarum is also part of the normal flora that can regulate the intestinal microflora and promote intestinal health. Some strains of L. plantarum are powerful probiotics that induce and modulate the innate and adaptive immune responses. Due to its outstanding immunoregulatory capacities, an increasing number of studies have examined the use of probiotic L. plantarum strains as natural immune adjuvants or alternative live vaccine carriers. The present review summarizes the main immunomodulatory characteristics of L. plantarum and discusses the preliminary immunological effects of L. plantarum as a vaccine adjuvant and delivery carrier. Different methods for improving the immune capacities of recombinant vector vaccines are also discussed.
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Affiliation(s)
- Guiting He
- Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang, 421001, Hunan, China
| | - Huanbing Long
- Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang, 421001, Hunan, China
| | - Jiarong He
- Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang, 421001, Hunan, China
| | - Cuiming Zhu
- Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang, 421001, Hunan, China.
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13
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Campagnoli LIM, Marchesi N, Varesi A, Morozzi M, Mascione L, Ricevuti G, Esposito C, Galeotti N, Pascale A. New therapeutic avenues in multiple sclerosis: Is there a place for gut microbiota-based treatments? Pharmacol Res 2024; 209:107456. [PMID: 39389400 DOI: 10.1016/j.phrs.2024.107456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/30/2024] [Accepted: 10/07/2024] [Indexed: 10/12/2024]
Abstract
The bidirectional interaction between the gut and the central nervous system (CNS), the so-called gut microbiota-brain axis, is reported to influence brain functions, thus having a potential impact on the development or the progression of several neurodegenerative disorders. Within this context, it has been documented that multiple sclerosis (MS), an autoimmune inflammatory, demyelinating, and neurodegenerative disease of the CNS, is associated with gastrointestinal symptoms, including constipation, dysphagia, and faecal incontinence. Moreover, some evidence suggests the existence of an altered gut microbiota (GM) composition in MS patients with respect to healthy individuals, as well as the potential influence of GM dysbiosis on typical MS features, including increased intestinal permeability, disruption of blood-brain barrier integrity, chronic inflammation, and altered T cells differentiation. Starting from these assumptions, the possible involvement of GM alteration in MS pathogenesis seems likely, and its restoration could represent a supplemental beneficial strategy against this disabling disease. In this regard, the present review will explore possible preventive approaches (including several dietary interventions, the administration of probiotics, prebiotics, synbiotics, and postbiotics, and the use of faecal microbiota transplantation) to be pursued as prophylaxis or in combination with pharmacological treatments with the aim of re-establishing a proper GM, thus helping to prevent the development of this disease or to manage it by alleviating symptoms or slowing down its progression.
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Affiliation(s)
| | - Nicoletta Marchesi
- Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
| | - Angelica Varesi
- Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Martina Morozzi
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
| | - Linda Mascione
- Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy
| | | | - Ciro Esposito
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy; Nephrology and dialysis unit, ICS S. Maugeri SPA SB Hospital, Pavia, Italy; High School in Geriatrics, University of Pavia, Italy
| | - Nicoletta Galeotti
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
| | - Alessia Pascale
- Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
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14
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Di Chiano M, Sallustio F, Fiocco D, Rocchetti MT, Spano G, Pontrelli P, Moschetta A, Gesualdo L, Gadaleta RM, Gallone A. Psychobiotic Properties of Lactiplantibacillus plantarum in Neurodegenerative Diseases. Int J Mol Sci 2024; 25:9489. [PMID: 39273435 PMCID: PMC11394828 DOI: 10.3390/ijms25179489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/26/2024] [Accepted: 08/29/2024] [Indexed: 09/15/2024] Open
Abstract
Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut-brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut-brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.
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Affiliation(s)
- Mariagiovanna Di Chiano
- Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
| | - Fabio Sallustio
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
| | - Daniela Fiocco
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Maria Teresa Rocchetti
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Giuseppe Spano
- Department of Agriculture Food Natural Science Engineering (DAFNE), University of Foggia, 71122 Foggia, Italy
| | - Paola Pontrelli
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
- National Institute for Biostructure and Biosystems (INBB), Viale delle Medaglie d'Oro n. 305, 00136 Roma, Italy
| | - Loreto Gesualdo
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
| | - Raffaella Maria Gadaleta
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
- National Institute for Biostructure and Biosystems (INBB), Viale delle Medaglie d'Oro n. 305, 00136 Roma, Italy
| | - Anna Gallone
- Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
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15
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Olejnik P, Buczma K, Cudnoch-Jędrzejewska A, Kasarełło K. Involvement of gut microbiota in multiple sclerosis-review of a new pathophysiological hypothesis and potential treatment target. Immunol Res 2024; 72:554-565. [PMID: 38446328 DOI: 10.1007/s12026-024-09471-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 02/29/2024] [Indexed: 03/07/2024]
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood-brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS.
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Affiliation(s)
- Piotr Olejnik
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| | - Kasper Buczma
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| | - Agnieszka Cudnoch-Jędrzejewska
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| | - Kaja Kasarełło
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
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16
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Taghizadeh Ghassab F, Shamlou Mahmoudi F, Taheri Tinjani R, Emami Meibodi A, Zali MR, Yadegar A. Probiotics and the microbiota-gut-brain axis in neurodegeneration: Beneficial effects and mechanistic insights. Life Sci 2024; 350:122748. [PMID: 38843992 DOI: 10.1016/j.lfs.2024.122748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/21/2024] [Accepted: 05/23/2024] [Indexed: 06/10/2024]
Abstract
Neurodegenerative diseases (NDs) are a group of heterogeneous disorders with a high socioeconomic burden. Although pharmacotherapy is currently the principal therapeutic approach for the management of NDs, mounting evidence supports the notion that the protracted application of available drugs would abate their dopaminergic outcomes in the long run. The therapeutic application of microbiome-based modalities has received escalating attention in biomedical works. In-depth investigations of the bidirectional communication between the microbiome in the gut and the brain offer a multitude of targets for the treatment of NDs or maximizing the patient's quality of life. Probiotic administration is a well-known microbial-oriented approach to modulate the gut microbiota and potentially influence the process of neurodegeneration. Of note, there is a strong need for further investigation to map out the mechanistic prospects for the gut-brain axis and the clinical efficacy of probiotics. In this review, we discuss the importance of microbiome modulation and hemostasis via probiotics, prebiotics, postbiotics and synbiotics in ameliorating pathological neurodegenerative events. Also, we meticulously describe the underlying mechanism of action of probiotics and their metabolites on the gut-brain axis in different NDs. We suppose that the present work will provide a functional direction for the use of probiotic-based modalities in promoting current practical treatments for the management of neurodegenerative-related diseases.
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Affiliation(s)
- Fatemeh Taghizadeh Ghassab
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Shamlou Mahmoudi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reyhaneh Taheri Tinjani
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Armitasadat Emami Meibodi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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17
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Saadh MJ, Ahmed HM, Alani ZK, Al Zuhairi RAH, Almarhoon ZM, Ahmad H, Ubaid M, Alwan NH. The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis. Neuromolecular Med 2024; 26:14. [PMID: 38630350 DOI: 10.1007/s12017-024-08783-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 03/08/2024] [Indexed: 04/19/2024]
Abstract
Multiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as short-chain fatty acids (SCFAs). These molecules may serve as vital molecular signals or metabolic substances regulating host cellular metabolism in the intricate interplay between microbiota and the host. A current emphasis lies on optimizing the health-promoting attributes of colonic bacteria to mitigate urinary tract issues through dietary management. This review aims to spotlight recent investigations on the impact of SCFAs on immune cells pivotal in MS, the involvement of gut microbiota and SCFAs in MS development, and the considerable influence of probiotics on gastrointestinal disruptions in MS. Comprehending the gut-CNS connection holds promise for the development of innovative therapeutic approaches, particularly probiotic-based supplements, for managing MS.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | - Hani Moslem Ahmed
- Department of Dental Industry Techniques, Al-Noor University College, Nineveh, Iraq
| | - Zaid Khalid Alani
- College of Health and Medical Technical, Al-Bayan University, Baghdad, Iraq
| | | | - Zainab M Almarhoon
- Department of Chemistry, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Hijaz Ahmad
- Section of Mathematics, International Telematic University Uninettuno, Corso Vittorio Emanuele II, 39, 00186, Rome, Italy.
- Center for Applied Mathematics and Bioinformatics, Gulf University for Science and Technology, Mubarak Al-Abdullah, Kuwait.
- Department of Computer Science and Mathematics, Lebanese American University, Beirut, Lebanon.
| | - Mohammed Ubaid
- Medical Technical College, Al-Farahidi University, Baghdad, Iraq
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18
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Zißler J, Rothhammer V, Linnerbauer M. Gut-Brain Interactions and Their Impact on Astrocytes in the Context of Multiple Sclerosis and Beyond. Cells 2024; 13:497. [PMID: 38534341 PMCID: PMC10968834 DOI: 10.3390/cells13060497] [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: 01/29/2024] [Revised: 03/04/2024] [Accepted: 03/12/2024] [Indexed: 03/28/2024] Open
Abstract
Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) that leads to physical and cognitive impairment in young adults. The increasing prevalence of MS underscores the critical need for innovative therapeutic approaches. Recent advances in neuroimmunology have highlighted the significant role of the gut microbiome in MS pathology, unveiling distinct alterations in patients' gut microbiota. Dysbiosis not only impacts gut-intrinsic processes but also influences the production of bacterial metabolites and hormones, which can regulate processes in remote tissues, such as the CNS. Central to this paradigm is the gut-brain axis, a bidirectional communication network linking the gastrointestinal tract to the brain and spinal cord. Via specific routes, bacterial metabolites and hormones can influence CNS-resident cells and processes both directly and indirectly. Exploiting this axis, novel therapeutic interventions, including pro- and prebiotic treatments, have emerged as promising avenues with the aim of mitigating the severity of MS. This review delves into the complex interplay between the gut microbiome and the brain in the context of MS, summarizing current knowledge on the key signals of cross-organ crosstalk, routes of communication, and potential therapeutic relevance of the gut microbiome. Moreover, this review places particular emphasis on elucidating the influence of these interactions on astrocyte functions within the CNS, offering insights into their role in MS pathophysiology and potential therapeutic interventions.
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Affiliation(s)
| | - Veit Rothhammer
- Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany
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19
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Yin X, Liu W, Feng H, Huang J, Wang Q, Zhang Q, He J, Wang R. Bifidobacterium animalis subsp. lactis A6 attenuates hippocampal damage and memory impairments in an ADHD rat model. Food Funct 2024; 15:2668-2678. [PMID: 38374797 DOI: 10.1039/d3fo04665f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2024]
Abstract
Attention deficit hyperactivity disorder (ADHD) is commonly accompanied by learning and memory deficits. This study aimed to demonstrate the effects of probiotic Bifidobacterium animalis subsp. lactis A6 (BAA6) on behaviour and memory function in spontaneously hypertensive rats (SHRs). The results showed that BAA6 treatment ameliorated spatial working memory deficits and inhibited hippocampal neuron loss in SHRs. The levels of neurotransmitters such as acetylcholine, dopamine, and norepinephrine, and the brain derived neurotrophic factor increased and that of glutamate decreased in the brain tissue of SHRs after BAA6 administration. Moreover, BAA6 reduced the levels of pro-inflammatory cytokines TNF-α and IL-1β, and increased the levels of anti-inflammatory IL-10 and antioxidant glutathione in SHRs. 16S rRNA high-throughput sequencing showed that BAA6 treatment changed the gut microbiota composition. BAA6 promoted beneficial Lactobacillus, Romboutsia, Blautia, and Turicibacter, and decreased the enrichment of bacterial genera such as Dietzia, Sporosarcina, Brevibacterium, NK4A214_group, Atopostipes, and Facklamia negatively associated with neurotransmitter release and anti-inflammatory effects in SHRs. Together, these results suggested that BAA6 improved memory function by ameliorating hippocampal damage, abnormal neurotransmitter release and cerebral inflammation by reshaping the gut microbiota in SHRs. This study provides a scientific basis for the development and application of BAA6 as a promising dietary intervention to reduce the risk of ADHD.
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Affiliation(s)
- Xindi Yin
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
| | - Weichen Liu
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
- National Center of Technology Innovation for Dairy, Hohhot 010000, China
| | - Haihong Feng
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
- Hebei Engineering Research Center of Animal Product, Langfang 065200, China
| | - Jiaqiang Huang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
| | - Qi Wang
- Xinjiang Golden Camel Investment Co., Ltd., Wulumuqi 830039, China
| | - Qi Zhang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
| | - Jingjing He
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China.
| | - Ran Wang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
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20
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Nekrasova I, Glebezdina N, Maslennikova I, Danchenko I, Shirshev S. Estriol and commensal microflora strains regulate innate lymphoid cells functional activity in multiple sclerosis. Mult Scler Relat Disord 2024; 83:105453. [PMID: 38277978 DOI: 10.1016/j.msard.2024.105453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/08/2024] [Accepted: 01/17/2024] [Indexed: 01/28/2024]
Abstract
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of immunity cells - innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS. In this work, we studied phenotypic characteristics of ILC in MS patients in comparison with healthy donors after 48 h incubation with pregnancy hormone estriol (E3) and commensal microflora cells. To activate ILC, strains of Ecsherichia coli K12 and Lactobacillus plantarum 8R-A3 were used. ILC phenotype was assessed by flow cytometry using monoclonal antibody staining. It has been established that E3 and bacterial factors are able to regulate the maturation of ILC subtypes and their cytokines in different ways. In general, the studied factors influence the phenotypic changes in ILC cells, leading to the transition from one type to another, both in healthy donors and in MS patients.
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Affiliation(s)
- Irina Nekrasova
- Perm Federal Research Center UB RAS, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Goleva str., 13, Perm 614081, Russia.
| | - Natalia Glebezdina
- Perm Federal Research Center UB RAS, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Goleva str., 13, Perm 614081, Russia
| | - Irina Maslennikova
- Perm Federal Research Center UB RAS, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Goleva str., 13, Perm 614081, Russia; Perm State Medical University named after E.A. Wagner, Perm, Russia
| | - Irina Danchenko
- Perm State Medical University named after E.A. Wagner, Perm, Russia
| | - Sergei Shirshev
- Perm Federal Research Center UB RAS, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Goleva str., 13, Perm 614081, Russia
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21
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Ibrahim SM, Kamel AS, Ahmed KA, Mohammed RA, Essam RM. The preferential effect of Clemastine on F3/Contactin-1/Notch-1 compared to Jagged-1/Notch-1 justifies its remyelinating effect in an experimental model of multiple sclerosis in rats. Int Immunopharmacol 2024; 128:111481. [PMID: 38232534 DOI: 10.1016/j.intimp.2023.111481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 12/30/2023] [Accepted: 12/30/2023] [Indexed: 01/19/2024]
Abstract
Clemastine (CLM) is repurposed to enhance remyelination in multiple sclerosis (MS) patients. CLM blocks histamine and muscarinic receptors as negative regulators to oligodendrocyte differentiation. These receptors are linked to the canonical and non-canonical Notch-1 signaling via specific ligands; Jagged-1 and F3/Contactin-1, respectively. Yet, there are no previous studies showing the influence of CLM on Notch entities. Herein, the study aimed to investigate to which extent CLM aligns to one of the two Notch-1 arms in experimental autoimmune encephalomyelitis (EAE) rat model. Three groups were utilized where first group received vehicles. The second group was injected by spinal cord homogenate mixed with complete Freund's adjuvant on days 0 and 7. In the third group, CLM (5 mg/kg/day; p.o) was administered for 15 days starting from the day of the first immunization. CLM ameliorated EAE-associated motor and gripping impairment in rotarod, open-field, and grip strength arena beside sensory anomalies in hot plate, cold allodynia, and mechanical Randall-Selitto tests. Additionally, CLM alleviated depressive mood observed in tail suspension test. These findings harmonized with histopathological examinations of Luxol-fast blue stain together with enhanced immunostaining of myelin basic protein and oligodendrocyte lineage gene 2 in corpus callosum and spinal cord. Additionally, CLM enhanced oligodendrocyte myelination and maturation by increasing 2',3'-cyclic nucleotide 3'-phosphodiesterase, proteolipid protein, aspartoacylase as well. CLM restored the level of F3/Contactin-1 in the diseased rats over Jagged-1 level; the ligand of the canonical pathway. This was accompanied by elevated gene expression of Deltex-1 and reduced hairy and enhancer-of-split homologs 1 and 5. Additionally, CLM suppressed microglial and astrocyte activation via reducing the expression of ionized calcium-binding adaptor molecule-1 as well as glial fibrillary acidic protein, respectively. These results outlined the remyelinating beneficence of CLM which could be due to augmenting the non-canonical Notch-1 signaling over the canonical one.
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Affiliation(s)
- Sherehan M Ibrahim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Ahmed S Kamel
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt
| | - Kawkab A Ahmed
- Pathology Department, Faculty of Veterinary Medicine, Cairo University, Egypt
| | - Reham A Mohammed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Reham M Essam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Biology Department, School of Pharmacy, Newgiza University, Giza, Egypt
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22
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Sultana OF, Hia RA, Reddy PH. A Combinational Therapy for Preventing and Delaying the Onset of Alzheimer's Disease: A Focus on Probiotic and Vitamin Co-Supplementation. Antioxidants (Basel) 2024; 13:202. [PMID: 38397800 PMCID: PMC10886126 DOI: 10.3390/antiox13020202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/27/2024] [Accepted: 02/02/2024] [Indexed: 02/25/2024] Open
Abstract
Alzheimer's disease is a progressive neurodegenerative disorder with a complex etiology, and effective interventions to prevent or delay its onset remain a global health challenge. In recent years, there has been growing interest in the potential role of probiotic and vitamin supplementation as complementary strategies for Alzheimer's disease prevention. This review paper explores the current scientific literature on the use of probiotics and vitamins, particularly vitamin A, D, E, K, and B-complex vitamins, in the context of Alzheimer's disease prevention and management. We delve into the mechanisms through which probiotics may modulate gut-brain interactions and neuroinflammation while vitamins play crucial roles in neuronal health and cognitive function. The paper also examines the collective impact of this combinational therapy on reducing the risk factors associated with Alzheimer's disease, such as oxidative stress, inflammation, and gut dysbiosis. By providing a comprehensive overview of the existing evidence and potential mechanisms, this review aims to shed light on the promise of probiotic and vitamin co-supplementation as a multifaceted approach to combat Alzheimer's disease, offering insights into possible avenues for future research and clinical application.
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Affiliation(s)
- Omme Fatema Sultana
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA;
| | - Raksa Andalib Hia
- Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA;
| | - P. Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA;
- Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA;
- Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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23
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Jank L, Bhargava P. Relationship Between Multiple Sclerosis, Gut Dysbiosis, and Inflammation: Considerations for Treatment. Neurol Clin 2024; 42:55-76. [PMID: 37980123 DOI: 10.1016/j.ncl.2023.07.005] [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: 11/20/2023]
Abstract
Multiple sclerosis is associated with gut dysbiosis, marked by changes in the relative abundances of specific microbes, circulating gut-derived metabolites, and altered gut permeability. This gut dysbiosis promotes disease pathology by increasing circulating proinflammatory bacterial factors, reducing tolerogenic factors, inducing molecular mimicry, and changing microbial nutrient metabolism. Beneficial antiinflammatory effects of the microbiome can be harnessed in therapeutic interventions. In the future, it is essential to assess the efficacy of these therapies in randomized controlled clinical trials to help make dietary and gut dysbiosis management an integral part of multiple sclerosis care.
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Affiliation(s)
- Larissa Jank
- Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-144, Baltimore, MD 21287, USA
| | - Pavan Bhargava
- Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-144, Baltimore, MD 21287, USA.
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24
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Zhang W, Jia Q, Han M, Zhang X, Guo L, Sun S, Yin W, Bo C, Han R, Sai L. Bifidobacteria in disease: from head to toe. Folia Microbiol (Praha) 2024; 69:1-15. [PMID: 37644256 DOI: 10.1007/s12223-023-01087-3] [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] [Indexed: 08/31/2023]
Abstract
Bifidobacteria as a strictly anaerobic gram-positive bacteria, is widely distributed in the intestine, vagina and oral cavity, and is one of the first gut flora to colonize the early stages of life. Intestinal flora is closely related to health, and dysbiosis of intestinal flora, especially Bifidobacteria, has been found in a variety of diseases. Numerous studies have shown that in addition to maintaining intestinal homeostasis, Bifidobacteria may be involved in diseases covering all parts of the body, including the nervous system, respiratory system, genitourinary system and so on. This review collects evidence for the variation of Bifidobacteria in typical diseases among various systems, provides mild and effective therapeutic options for those diseases that are difficult to cure, and moves Bifidobacteria from basic research to further clinical applications.
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Affiliation(s)
- Weiliang Zhang
- Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, China
| | - Qiang Jia
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Mingming Han
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xin Zhang
- Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, China
| | - Limin Guo
- Rongcheng Municipal Hospital of Traditional Chinese Medicine, Rongcheng, Shandong, China
| | - Shichao Sun
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Shandong University of Traditional Chinese Medicine Doctoral candidate Class of 2022, Jinan, Shandong, China
| | - Wenhui Yin
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Cunxiang Bo
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Ru Han
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
| | - Linlin Sai
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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25
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Li N, Han X, Ruan M, Huang F, Yang L, Xu T, Wang H, Wu H, Shi S, Wang Y, Wu X, Wang S. Prebiotic inulin controls Th17 cells mediated central nervous system autoimmunity through modulating the gut microbiota and short chain fatty acids. Gut Microbes 2024; 16:2402547. [PMID: 39287045 PMCID: PMC11409507 DOI: 10.1080/19490976.2024.2402547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 08/20/2024] [Accepted: 09/04/2024] [Indexed: 09/19/2024] Open
Abstract
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.
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Affiliation(s)
- Ning Li
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Spine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinyan Han
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ming Ruan
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Spine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fei Huang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Liu Yang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tianhao Xu
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Spine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Huijun Wang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hui Wu
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Songshan Shi
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yongjun Wang
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Spine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaojun Wu
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shunchun Wang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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26
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Hoseinzadeh A, Mahmoudi M, Rafatpanah H, Rezaieyazdi Z, Tavakol Afshari J, Hosseini S, Esmaeili SA. A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment. Stem Cell Res Ther 2023; 14:358. [PMID: 38072921 PMCID: PMC10712058 DOI: 10.1186/s13287-023-03578-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/21/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease. METHODS Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons. RESULTS Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation. CONCLUSIONS Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties.
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Affiliation(s)
- Akram Hoseinzadeh
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Mahmoudi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Houshang Rafatpanah
- Immunology Research Centre, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Rezaieyazdi
- Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jalil Tavakol Afshari
- Faculty of Medicine, Department of Immunology, BuAli Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sara Hosseini
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed-Alireza Esmaeili
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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27
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Kujawa D, Laczmanski L, Budrewicz S, Pokryszko-Dragan A, Podbielska M. Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis. Gut Microbes 2023; 15:2274126. [PMID: 37979154 PMCID: PMC10730225 DOI: 10.1080/19490976.2023.2274126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 10/18/2023] [Indexed: 11/20/2023] Open
Abstract
Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.
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Affiliation(s)
- Dorota Kujawa
- Laboratory of Genomics & Bioinformatics, Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Lukasz Laczmanski
- Laboratory of Genomics & Bioinformatics, Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | | | | | - Maria Podbielska
- Laboratory of Microbiome Immunobiology, Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
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28
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Gavzy SJ, Kensiski A, Lee ZL, Mongodin EF, Ma B, Bromberg JS. Bifidobacterium mechanisms of immune modulation and tolerance. Gut Microbes 2023; 15:2291164. [PMID: 38055306 PMCID: PMC10730214 DOI: 10.1080/19490976.2023.2291164] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 11/30/2023] [Indexed: 12/07/2023] Open
Abstract
Bifidobacterium is a widely distributed commensal bacterial genus that displays beneficial pro-homeostatic and anti-inflammatory immunomodulatory properties. Depletion or absence of Bifidobacterium in humans and model organisms is associated with autoimmune responses and impaired immune homeostasis. At the cellular level, Bifidobacterium upregulates suppressive regulatory T cells, maintains intestinal barrier function, modulates dendritic cell and macrophage activity, and dampens intestinal Th2 and Th17 programs. While there has been a large volume of literature characterizing the probiotic properties of various Bifidobacterial species, the likely multifactorial mechanisms underlying these effects remain elusive, in particular, its immune tolerogenic effect. However, recent work has shed light on Bifidobacterium surface structural polysaccharide and protein elements, as well as its metabolic products, as commensal mediators of immune homeostasis. This review aims to discuss several mechanisms Bifidobacterium utilizes for immune modulation as well as their indirect impact on the regulation of gut microbiome structure and function, from structural molecules to produced metabolites. These mechanisms are pertinent to an increasingly networked understanding of immune tolerance and homeostasis in health and disease.
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Affiliation(s)
- Samuel J Gavzy
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Allison Kensiski
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Zachariah L Lee
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Emmanuel F Mongodin
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Bing Ma
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Jonathan S Bromberg
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
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29
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Essmat N, Karádi DÁ, Zádor F, Király K, Fürst S, Al-Khrasani M. Insights into the Current and Possible Future Use of Opioid Antagonists in Relation to Opioid-Induced Constipation and Dysbiosis. Molecules 2023; 28:7766. [PMID: 38067494 PMCID: PMC10708112 DOI: 10.3390/molecules28237766] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 11/21/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
Opioid receptor agonists, particularly those that activate µ-opioid receptors (MORs), are essential analgesic agents for acute or chronic mild to severe pain treatment. However, their use has raised concerns including, among others, intestinal dysbiosis. In addition, growing data on constipation-evoked intestinal dysbiosis have been reported. Opioid-induced constipation (OIC) creates an obstacle to continuing treatment with opioid analgesics. When non-opioid therapies fail to overcome the OIC, opioid antagonists with peripheral, fast first-pass metabolism, and gastrointestinal localized effects remain the drug of choice for OIC, which are discussed here. At first glance, their use seems to only be restricted to constipation, however, recent data on OIC-related dysbiosis and its contribution to the appearance of several opioid side effects has garnered a great of attention from researchers. Peripheral MORs have also been considered as a future target for opioid analgesics with limited central side effects. The properties of MOR antagonists counteracting OIC, and with limited influence on central and possibly peripheral MOR-mediated antinociception, will be highlighted. A new concept is also proposed for developing gut-selective MOR antagonists to treat or restore OIC while keeping peripheral antinociception unaffected. The impact of opioid antagonists on OIC in relation to changes in the gut microbiome is included.
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Affiliation(s)
- Nariman Essmat
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1445 Budapest, Hungary; (N.E.); (D.Á.K.); (F.Z.); (K.K.); (S.F.)
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Dávid Árpád Karádi
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1445 Budapest, Hungary; (N.E.); (D.Á.K.); (F.Z.); (K.K.); (S.F.)
| | - Ferenc Zádor
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1445 Budapest, Hungary; (N.E.); (D.Á.K.); (F.Z.); (K.K.); (S.F.)
| | - Kornél Király
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1445 Budapest, Hungary; (N.E.); (D.Á.K.); (F.Z.); (K.K.); (S.F.)
| | - Susanna Fürst
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1445 Budapest, Hungary; (N.E.); (D.Á.K.); (F.Z.); (K.K.); (S.F.)
| | - Mahmoud Al-Khrasani
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1445 Budapest, Hungary; (N.E.); (D.Á.K.); (F.Z.); (K.K.); (S.F.)
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30
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Ghaiad HR, A Abd-Elmawla M, Gad ES, A Ahmed K, Abdelmonem M. Modulating miR-146a Expression by Hydrogen Sulfide Ameliorates Motor Dysfunction and Axonal Demyelination in Cuprizone-Induced Multiple Sclerosis. ACS Chem Neurosci 2023; 14:3047-3058. [PMID: 37585620 DOI: 10.1021/acschemneuro.3c00141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023] Open
Abstract
Multiple sclerosis (MS) is a progressive neuro-inflammatory and neuro-autoimmune disease. Although hydrogen sulfide has recently shown potential therapeutic impacts in different neurological diseases, its effects on MS are still obscure. MiR-146a is considered a vital target for different therapeutic approaches in treating MS. The present study is directed to explore the therapeutic effects of NaHS (hydrogen sulfide donor) on cuprizone-induced MS and to explore whether NaHS can mediate its effects via regulating miR-146a expression. A total of 28 male C57Bl/6 mice were divided into 4 groups; control, cuprizone-intoxicated, NaHS control (100 μmol/kg/day, i.p), and NaHS-treated groups. Intriguingly, NaHS treatment managed to improve locomotor coordination and curb neuronal inflammation and demyelination as evidenced by hematoxylin & eosin, and Luxol fast blue staining and the increased myelin basic protein (MBP) content. Additionally, NaHS reduced interleukin-1 receptor-associated kinase-1 (IRAK-1), nuclear transcription factor kappa B (NF-κB), interleukin (IL)-17, and IL-1β brain levels along with downregulation of miR-146a expression compared with the untreated cuprizone-intoxicated group. Furthermore, NaHS-treated animals revealed much less oxidative stress compared to the untreated animals as evidenced by elevated glutathione and reduced malondialdehyde contents. Altogether, the current work reported that NaHS could improve motor dysfunction and reduce axonal demyelination, oxidative stress, as well as neuro-inflammation in mice with MS. Thus, using H2S-releasing compounds could be a promising approach in MS treatment strategies. The mechanism of these beneficial effects may involve the regulation of miR-146a/NF-κB/IL-1β axis.
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Affiliation(s)
- Heba R Ghaiad
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Enas S Gad
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, Ismailia 45511, Egypt
| | - Kawkab A Ahmed
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Cairo 12211, Egypt
| | - Maha Abdelmonem
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
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31
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Shakya AK, Mallick B, Nandakumar KS. A Perspective on Oral Immunotherapeutic Tools and Strategies for Autoimmune Disorders. Vaccines (Basel) 2023; 11:1031. [PMID: 37376420 DOI: 10.3390/vaccines11061031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 05/19/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Oral immune tolerance is a physiological process to achieve tolerance against autoimmunity by oral ingestion of self-antigen(s) or other therapeutics. At the cellular level, oral tolerance suppresses autoimmune diseases by activating FoxP-positive and -negative regulatory T cells (Tregs) and/or causing clonal anergy or deletion of autoreactive T cells, affecting B cell tolerance. However, oral delivery of antigens/biologics is challenging due to their instability in the harsh environment of the gastrointestinal (GI) tract. Several antigen/drug delivery tools and approaches, including micro/nanoparticles and transgenic plant-based delivery systems, have been explored to demonstrate oral immune tolerance for different autoimmune diseases successfully. However, despite the effectiveness, variation in results, dose optimization, and undesirable immune system activation are the limitations of the oral approach to further advancement. From this perspective, the current review discusses the oral tolerance phenomenon, cellular mechanisms, antigen delivery tools and strategies, and its challenges.
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Affiliation(s)
| | - Buddhadev Mallick
- Department of Zoology, Raniganj Girls College, Bardhaman 713358, West Bengal, India
| | - Kutty Selva Nandakumar
- Department of Environmental and Biosciences, School of Business, Innovation, and Sustainability, Halmstad University, 301 18 Halmstad, Sweden
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32
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Bronzini M, Maglione A, Rosso R, Matta M, Masuzzo F, Rolla S, Clerico M. Feeding the gut microbiome: impact on multiple sclerosis. Front Immunol 2023; 14:1176016. [PMID: 37304278 PMCID: PMC10248010 DOI: 10.3389/fimmu.2023.1176016] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 05/02/2023] [Indexed: 06/13/2023] Open
Abstract
Multiple sclerosis (MS) is a multifactorial neurological disease characterized by chronic inflammation and immune-driven demyelination of the central nervous system (CNS). The rising number of MS cases in the last decade could be partially attributed to environmental changes, among which the alteration of the gut microbiome driven by novel dietary habits is now of particular interest. The intent of this review is to describe how diet can impact the development and course of MS by feeding the gut microbiome. We discuss the role of nutrition and the gut microbiota in MS disease, describing preclinical studies on experimental autoimmune encephalomyelitis (EAE) and clinical studies on dietary interventions in MS, with particular attention to gut metabolites-immune system interactions. Possible tools that target the gut microbiome in MS, such as the use of probiotics, prebiotics and postbiotics, are analyzed as well. Finally, we discuss the open questions and the prospects of these microbiome-targeted therapies for people with MS and for future research.
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Affiliation(s)
- Matteo Bronzini
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
| | - Alessandro Maglione
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
| | - Rachele Rosso
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
| | - Manuela Matta
- San Luigi Gonzaga University Hospital, Orbassano, Italy
| | | | - Simona Rolla
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
| | - Marinella Clerico
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
- San Luigi Gonzaga University Hospital, Orbassano, Italy
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33
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Hoffman K, Brownell Z, Doyle WJ, Ochoa-Repáraz J. The immunomodulatory roles of the gut microbiome in autoimmune diseases of the central nervous system: Multiple sclerosis as a model. J Autoimmun 2023; 137:102957. [PMID: 36435700 PMCID: PMC10203067 DOI: 10.1016/j.jaut.2022.102957] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 11/14/2022] [Indexed: 11/24/2022]
Abstract
The gut-associated lymphoid tissue is a primary activation site for immune responses to infection and immunomodulation. Experimental evidence using animal disease models suggests that specific gut microbes significantly regulate inflammation and immunoregulatory pathways. Furthermore, recent clinical findings indicate that gut microbes' composition, collectively named gut microbiota, is altered under disease state. This review focuses on the functional mechanisms by which gut microbes promote immunomodulatory responses that could be relevant in balancing inflammation associated with autoimmunity in the central nervous system. We also propose therapeutic interventions that target the composition of the gut microbiota as immunomodulatory mechanisms to control neuroinflammation.
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Affiliation(s)
- Kristina Hoffman
- Department of Biological Sciences, Boise State University, Boise, ID, 83725, USA
| | - Zackariah Brownell
- Department of Biological Sciences, Arizona State University, Tempe, AZ, 85281, USA
| | - William J Doyle
- Department of Biological Sciences, Boise State University, Boise, ID, 83725, USA
| | - Javier Ochoa-Repáraz
- Department of Biological Sciences, Boise State University, Boise, ID, 83725, USA.
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Ojha S, Patil N, Jain M, Kole C, Kaushik P. Probiotics for Neurodegenerative Diseases: A Systemic Review. Microorganisms 2023; 11:microorganisms11041083. [PMID: 37110506 PMCID: PMC10140855 DOI: 10.3390/microorganisms11041083] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/12/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Neurodegenerative disorders (ND) are a group of conditions that affect the neurons in the brain and spinal cord, leading to their degeneration and eventually causing the loss of function in the affected areas. These disorders can be caused by a range of factors, including genetics, environmental factors, and lifestyle choices. Major pathological signs of these diseases are protein misfolding, proteosomal dysfunction, aggregation, inadequate degradation, oxidative stress, free radical formation, mitochondrial dysfunctions, impaired bioenergetics, DNA damage, fragmentation of Golgi apparatus neurons, disruption of axonal transport, dysfunction of neurotrophins (NTFs), neuroinflammatory or neuroimmune processes, and neurohumoral symptoms. According to recent studies, defects or imbalances in gut microbiota can directly lead to neurological disorders through the gut-brain axis. Probiotics in ND are recommended to prevent cognitive dysfunction, which is a major symptom of these diseases. Many in vivo and clinical trials have revealed that probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei, etc.) are effective candidates against the progression of ND. It has been proven that the inflammatory process and oxidative stress can be modulated by modifying the gut microbiota with the help of probiotics. As a result, this study provides an overview of the available data, bacterial variety, gut-brain axis defects, and probiotics' mode of action in averting ND. A literature search on particular sites, including PubMed, Nature, and Springer Link, has identified articles that might be pertinent to this subject. The search contains the following few groups of terms: (1) Neurodegenerative disorders and Probiotics OR (2) Probiotics and Neurodegenerative disorders. The outcomes of this study aid in elucidating the relationship between the effects of probiotics on different neurodegenerative disorders. This systematic review will assist in discovering new treatments in the future, as probiotics are generally safe and cause mild side effects in some cases in the human body.
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Affiliation(s)
- Sandhya Ojha
- Cell & Developmental Biology Laboratory, Centre of Research for Development, Parul University, Vadodara 391760, India
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, India
| | - Nil Patil
- Cell & Developmental Biology Laboratory, Centre of Research for Development, Parul University, Vadodara 391760, India
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, India
| | - Mukul Jain
- Cell & Developmental Biology Laboratory, Centre of Research for Development, Parul University, Vadodara 391760, India
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, India
| | | | - Prashant Kaushik
- Instituto de Conservacióny Mejora de la Agrodiversidad Valenciana, Universitat Politècnica de València, 46022 Valencia, Spain
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Hashemi B, Abdollahi M, Abbaspour-Aghdam S, Hazrati A, Malekpour K, Meshgi S, Kafil HS, Ghazi F, Yousefi M, Roshangar L, Ahmadi M. The effect of probiotics on immune responses and their therapeutic application: A new treatment option for multiple sclerosis. Biomed Pharmacother 2023; 159:114195. [PMID: 36630847 DOI: 10.1016/j.biopha.2022.114195] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/10/2022] [Accepted: 12/28/2022] [Indexed: 01/12/2023] Open
Abstract
Multiple sclerosis (MS) is known as a chronic inflammatory disease (CID) that affects the central nervous system and leads to nerve demyelination. However, the exact cause of MS is unknown, but immune system regulation and inhibiting the function of inflammatory pathways may have a beneficial effect on controlling and improving the disease. Studies show that probiotics can alter the gut microbiome, thereby improving and affecting the immune system and inflammatory responses in patients with MS. The results show that probiotics have a good effect on the recovery of patients with MS in humans and animals. The present study investigated the effect of probiotics and possible therapeutic mechanisms of probiotics on immune cells and inflammatory cytokines. This review article showed that probiotics could improve immune cells and inflammatory cytokines in patients with MS and can play an effective role in disease management and control.
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Affiliation(s)
- Behnam Hashemi
- Department of Bacteriology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
| | - Maryam Abdollahi
- Department of Bacteriology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
| | - Sanaz Abbaspour-Aghdam
- Department of Clinical Biochemistry and Applied Cell Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ali Hazrati
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kosar Malekpour
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shahla Meshgi
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farhood Ghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Ahmadi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Michalickova D, Kramarikova I, Ozturk HK, Kucera T, Vacik T, Hrncir T, Kutinova Canova N, Sima M, Slanar O. Detection of galanin receptors in the spinal cord in experimental autoimmune encephalomyelitis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2023; 167:36-42. [PMID: 35147137 DOI: 10.5507/bp.2022.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 01/28/2022] [Indexed: 11/23/2022] Open
Abstract
AIMS The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The aims of the present study were to investigate the expression of galanin receptors (GalR1, GalR2, GalR3) in the spinal cords in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) using qPCR analysis and to determine GalR1 cellular localization (oligodendrocytes, microglia, astrocytes, ependymal cells, and endothelial cells in the capillaries) by immunohistochemistry. METHODS Twelve samples from the EAE group and 14 samples from the control group were analyzed. Spinal cords samples were obtained at the peak of the EAE disease. RESULTS The GalR1 mRNA level was significantly decreased in the EAE mice compared with the controls (P=0.016), whereas the mRNA levels of GalR2 and GalR3 were not significantly different for the EAE and the control mice. No significant correlations were found between the severity of the EAE disease and the mRNA levels of GalR1, GalR2 and GalR3. Immunochemical detection of the GalR1 revealed its expression in the ependymal and endothelial cells. Additionally, a weak GalR1 immunoreactivity was occasionally detected in the oligodendrocytes. CONCLUSION This study provides additional evidence of galanin involvement in EAE pathophysiology, but this has to be further investigated.
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Affiliation(s)
- Danica Michalickova
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Ivana Kramarikova
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Hatice Kubra Ozturk
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Tomas Kucera
- Institute of Histology and Embryology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Tomas Vacik
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Tomas Hrncir
- Institute of Microbiology, Czech Academy of Sciences, Novy Hradek, Czech Republic
| | - Nikolina Kutinova Canova
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Martin Sima
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Ondrej Slanar
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
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Khalifa A, Ibrahim HIM, Sheikh A, Khalil HE. Probiotic-Fermented Camel Milk Attenuates Neurodegenerative Symptoms via SOX5/miR-218 Axis Orchestration in Mouse Models. Pharmaceuticals (Basel) 2023; 16:357. [PMID: 36986457 PMCID: PMC10059028 DOI: 10.3390/ph16030357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/19/2023] [Accepted: 02/23/2023] [Indexed: 03/02/2023] Open
Abstract
Multiple sclerosis is an autoimmune-mediated myelin damage disorder in the central nervous system that is widespread among neurological patients. It has been demonstrated that several genetic and epigenetic factors control autoimmune encephalomyelitis (EAE), a murine model of MS, through CD4+ T-cell population quantity. Alterations in the gut microbiota influence neuroprotectiveness via unexplored mechanisms. In this study, the ameliorative effect of Bacillus amyloliquefaciens fermented in camel milk (BEY) on an autoimmune-mediated neurodegenerative model using myelin oligodendrocyte glycoprotein/complete fraud adjuvant/pertussis toxin (MCP)-immunized C57BL6j mice is investigated. Anti-inflammatory activity was confirmed in the in vitro cell model, and inflammatory cytokines interleukins IL17 (from EAE 311 to BEY 227 pg/mL), IL6 (from EAE 103 to BEY 65 pg/mL), IFNγ (from EAE 423 to BEY 243 pg/mL) and TGFβ (from EAE 74 to BEY 133 pg/mL) were significantly reduced in BEY-treated mice. The epigenetic factor miR-218-5P was identified and confirmed its mRNA target SOX-5 using in silico tools and expression techniques, suggesting SOX5/miR-218-5p could serve as an exclusive diagnostic marker for MS. Furthermore, BEY improved the short-chain fatty acids, in particular butyrate (from 0.57 to 0.85 µM) and caproic (from 0.64 to 1.33 µM) acids, in the MCP mouse group. BEY treatment significantly regulated the expression of inflammatory transcripts in EAE mice and upregulated neuroprotective markers such as neurexin (from 0.65- to 1.22-fold) (p < 0.05), vascular endothelial adhesion molecules (from 0.41- to 0.76-fold) and myelin-binding protein (from 0.46- to 0.89-fold) (p < 0.03). These findings suggest that BEY could be a promising clinical approach for the curative treatment of neurodegenerative diseases and could promote the use of probiotic food as medicine.
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Affiliation(s)
- Ashraf Khalifa
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
- Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Hairul Islam Mohamed Ibrahim
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
- Molecular Biology Division, Pondicherry Centre for Biological Sciences and Educational Trust, Pondicherry 605004, India
| | - Abdullah Sheikh
- Camel Research Center, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Hany Ezzat Khalil
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
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Kumar N, Sahoo NK, Mehan S, Verma B. The importance of gut-brain axis and use of probiotics as a treatment strategy for multiple sclerosis. Mult Scler Relat Disord 2023; 71:104547. [PMID: 36805171 DOI: 10.1016/j.msard.2023.104547] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 01/16/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023]
Abstract
It has been shown that the dysbiosis of the gut's microbes substantially impacts CNS illnesses, including Alzheimer's, Parkinson's, autism, and autoimmune diseases like multiple sclerosis (MS). MS is a CNS-affected autoimmune demyelination condition. Through a two-way communication pathway known as the gut-brain axis, gut microbes communicate with the CNS. When there is a disruption in the gut microbiome, cytokines and other immune cells are secreted, which affects the BBB and gastrointestinal permeability. Recent research using animal models has revealed that the gut microbiota may greatly influence the pathophysiology of EAE/MS. Any change in the gut might increase inflammatory cytokinesand affect the quantity of SCFAs, and other metabolites that cause neuroinflammation and demyelination. In- vivo and in-vitro studies have concluded that probiotics affect the immune system and can be utilized to treat gastrointestinal dysbiosis. Any alteration in the gut microbial composition caused by probiotic intake may serve as a preventive and treatment strategy for MS. The major goal of this review is to emphasize an overview of recent research on the function of gut microbiota in the onset of MS and how probiotics have a substantial impact on gastrointestinal disruption in MS and other neuro disorders. It will be easier to develop new therapeutic approaches, particularly probiotic-based supplements, for treating multiple sclerosis (MS) if we know the link between the gut and CNS.
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Affiliation(s)
- Nitish Kumar
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh 201204, India.
| | - Nalini Kanta Sahoo
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh 201204, India
| | - Sidharth Mehan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, (An Autonomous College), Moga, Punjab 142001, India
| | - Bharti Verma
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh 201204, India
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Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers. Nutrients 2023; 15:nu15030550. [PMID: 36771257 PMCID: PMC9921734 DOI: 10.3390/nu15030550] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/24/2023] Open
Abstract
Multiple sclerosis (MS), a distinct autoimmune neuroinflammatory disorder, affects millions of people worldwide, including Saudi Arabia. Changes in the gut microbiome are linked to the development of neuroinflammation via mechanisms that are not fully understood. Prebiotics and probiotics in camel milk that has been fermented have a variety of health benefits. In this study, Bacillus amyloliquefaciens-supplemented camel milk (BASY) was used to assess its preventive effect on MS symptoms in a myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL6J mice model. To this end, MOG-induced experimental autoimmune encephalomyelitis (EAE) was established and the level of disease index, pathological scores, and anti-inflammatory markers of BASY-treated mice using macroscopic and microscopic examinations, qPCR and immunoblot were investigated. The results demonstrate that BASY significantly reduced the EAE disease index, increased total microbial load (2.5 fold), and improved the levels of the short-chain fatty acids propionic, butyric and caproic acids in the diseased mice group. Additionally, myeloperoxidase (MPO) proinflammatory cytokines (IL-1β, IL-6, IL-17, TNF-α) and anti-inflammatory cytokines (TGF-β) were regulated by BASY treatment. Significant suppression of MPO and VCAM levels were noticed in the BASY-treated group (from 168 to 111 µM and from 34 to 27 pg/mL, respectively), in comparison to the EAE group. BASY treatment significantly reduced the expression of inflammatory cytokines, inflammatory progression related transcripts, and inflammatory progression protein markers. In conclusion, BASY significantly reduced the symptoms of EAE mice and may be used to develop a probiotic-based diet to promote host gut health. The cumulative findings of this study confirm the significant neuroprotection of BASY in the MOG-induced mice model. They could also suggest a novel approach to the treatment of MS-associated disorders.
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Zhang ML, Li WX, Wang XY, Wu YL, Chen XF, Zhang H, Yang LQ, Wu CZ, Zhang SQ, Chen YL, Feng KR, Wang B, Niu L, Kong DX, Tang JF. Oxymatrine ameliorates experimental autoimmune encephalomyelitis by rebalancing the homeostasis of gut microbiota and reducing blood-brain barrier disruption. Front Cell Infect Microbiol 2023; 12:1095053. [PMID: 36710971 PMCID: PMC9878311 DOI: 10.3389/fcimb.2022.1095053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 12/20/2022] [Indexed: 01/15/2023] Open
Abstract
Background Increasing evidence suggests that gut dysbiosis can directly or indirectly affect the immune system through the brain-gut axis and play a role in the occurrence and development of Multiple sclerosis (MS). Oxymatrine (OMAT) has been shown to ameliorate the symptoms of MS in the classical experimental autoimmune encephalomyelitis (EAE) model of MS, but whether its therapeutic role is through the correction of gut dysbiosis, is unclear. Methods The effects of OMAT on intestinal flora and short-chain fatty acids in EAE model mice were evaluated by 16S rRNA sequencing and GC-MS/MS, respectively, and the function change of the blood-brain barrier and intestinal epithelial barrier was further tested by immunohistochemical staining, Evans Blue leakage detection, and RT-qPCR. Results The alpha and beta diversity in the feces of EAE mice were significantly different from that of the control group but recovered substantially after OMAT treatment. Besides, the OMAT treatment significantly affected the gut functional profiling and the abundance of genes associated with energy metabolism, amino acid metabolism, the immune system, infectious diseases, and the nervous system. OMAT also decreased the levels of isobutyric acid and isovaleric acid in EAE mice, which are significantly related to the abundance of certain gut microbes and were consistent with the reduced expression of TNF-a, IL-6, and IL-1b. Furthermore, OMAT treatment significantly increased the expression of ZO-1 and occludin in the brains and colons of EAE mice and decreased blood-brain barrier permeability. Conclusion OMAT may alleviate the clinical and pathological symptoms of MS by correcting dysbiosis, restoring gut ecological and functional microenvironment, and inhibiting immune cell-mediated inflammation to remodel the brain-gut axis.
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Affiliation(s)
- Ming-Liang Zhang
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China,Henan Province Engineering Research Center of Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Zhengzhou, China
| | - Wei-Xia Li
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China,Henan Province Engineering Research Center of Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Zhengzhou, China
| | - Xiao-Yan Wang
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China,Henan Province Engineering Research Center of Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Zhengzhou, China
| | - Ya-Li Wu
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Xiao-Fei Chen
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Hui Zhang
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Liu-Qing Yang
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Cheng-Zhao Wu
- Chengdu University of Chinese Medicine, Chengdu, China
| | - Shu-Qi Zhang
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yu-Long Chen
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
| | - Ke-Ran Feng
- Chengdu University of Chinese Medicine, Chengdu, China
| | - Bin Wang
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
| | - Lu Niu
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - De-Xin Kong
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jin-Fa Tang
- Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China,Henan Province Engineering Research Center of Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Zhengzhou, China,School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China,*Correspondence: Jin-Fa Tang,
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Súkeníková L, Černý V, Thon T, Roubalová R, Jirásková Zákostelská Z, Novotná O, Petrásková P, Boráková K, Kocourková I, Lodinová-Žádníková R, Musil Z, Kolářová L, Prokešová L, Valenta Z, Hrdý J. Effect of early postnatal supplementation of newborns with probiotic strain E. coli O83:K24:H31 on allergy incidence, dendritic cells, and microbiota. Front Immunol 2023; 13:1038328. [PMID: 36703968 PMCID: PMC9872645 DOI: 10.3389/fimmu.2022.1038328] [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: 09/06/2022] [Accepted: 12/20/2022] [Indexed: 01/11/2023] Open
Abstract
Introduction Probiotic administration seems to be a rational approach to promote maturation of the neonatal immune system. Mutual interaction of the microbiota with the host immune system is critical for the setting of appropriate immune responses including a tolerogenic one and thevmaintenance of homeostasis. On the other hand, our knowledge on the modes of actions of probiotics is still scarce. Methods In our study, probiotic strain Escherichia coli O83:K24:H31 (EcO83) was administered to neonates of allergic mothers (AMs; neonates with increased risk for allergy development) within 48 h after the delivery, and the impact of this early postnatal supplementation on allergy incidence and selected immune markers has been analyzed 10 years after the primary EcO83 administration. Results We have observed decreased allergy incidence in 10-year-old children supplemented with EcO83 (13 of 52 children were allergic) in comparison with non-supplemented children of AMs (16 of 42 children were allergic). The early postnatal EcO83 supplementation appeared to limit the allergy in the high-risk group (children of AMs) compared to that in the low-risk group (children of healthy mothers). Dendritic cells (DCs) in the peripheral blood of EcO83-supplemented children do not differ significantly in cell surface presence of CD83. The immunomodulatory capacity of EcO83 on DCs was tested in vitro as well. Both directly isolated myeloid and in vitro monocyte-derived DCs from cord blood increased CD83 expression together with interleukin (IL)-10 secretion after EcO83 stimulation. The effect of early postnatal EcO83 supplementation on the microbiota composition of 10-year-old children was characterized by next-generation sequencing, and we have not observed significant changes in the microbiota composition of EcO83-supplemented and non-supplemented children at the age of 10 years. Conclusions Early postnatal EcO83 supplementation appears to lower allergy incidence in children of AMs. It seems that the beneficial effect of EcO83 is mediated via modulation of DC functional capacities without impacting the microbiota composition. Larger-scale studies will be necessary to confirm these preliminary findings.
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Affiliation(s)
- Lenka Súkeníková
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Viktor Černý
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Tomáš Thon
- Institute of Microbiology, Academy of Sciences, Prague, Czechia
| | - Radka Roubalová
- Institute of Microbiology, Academy of Sciences, Prague, Czechia
| | | | - Olga Novotná
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Petra Petrásková
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Kristýna Boráková
- Department of Neonatology, Institute for the Care of Mother and Child, Prague, Czechia
| | - Ingrid Kocourková
- Department of Neonatology, Institute for the Care of Mother and Child, Prague, Czechia
| | | | - Zdeněk Musil
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Libuše Kolářová
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Ludmila Prokešová
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Zdeněk Valenta
- Department of Statistical Modelling, Institute of Computer Science of the Czech Academy of Sciences, Prague, Czechia
| | - Jiří Hrdý
- Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czechia,*Correspondence: Jiří Hrdý,
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42
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Updates on the Role of Probiotics against Different Health Issues: Focus on Lactobacillus. Int J Mol Sci 2022; 24:ijms24010142. [PMID: 36613586 PMCID: PMC9820606 DOI: 10.3390/ijms24010142] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
This review article is built on the beneficial effects of Lactobacillus against different diseases, and a special focus has been made on its effects against neurological disorders, such as depression, multiple sclerosis, Alzheimer's, and Parkinson's disease. Probiotics are live microbes, which are found in fermented foods, beverages, and cultured milk and, when administered in an adequate dose, confer health benefits to the host. They are known as "health-friendly bacteria", normally residing in the human gut and involved in maintaining homeostatic conditions. Imbalance in gut microbiota results in the pathophysiology of several diseases entailing the GIT tract, skin, immune system, inflammation, and gut-brain axis. Recently, the use of probiotics has gained tremendous interest, because of their profound effects on the management of these disease conditions. Recent findings suggest that probiotics enrichment in different human and mouse disease models showed promising beneficial effects and results in the amelioration of disease symptoms. Thus, this review focuses on the current probiotics-based products, different disease models, variable markers measured during trials, and evidence obtained from past studies on the use of probiotics in the prevention and treatment of different diseases, covering the skin to the central nervous system diseases.
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Dziedzic A, Saluk J. Probiotics and Commensal Gut Microbiota as the Effective Alternative Therapy for Multiple Sclerosis Patients Treatment. Int J Mol Sci 2022; 23:ijms232214478. [PMID: 36430954 PMCID: PMC9699268 DOI: 10.3390/ijms232214478] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/17/2022] [Accepted: 11/18/2022] [Indexed: 11/23/2022] Open
Abstract
The gut-brain axis (GBA) refers to the multifactorial interactions between the intestine microflora and the nervous, immune, and endocrine systems, connecting brain activity and gut functions. Alterations of the GBA have been revealed in people with multiple sclerosis (MS), suggesting a potential role in disease pathogenesis and making it a promising therapeutic target. Whilst research in this field is still in its infancy, a number of studies revealed that MS patients are more likely to exhibit modified microbiota, altered levels of short-chain fatty acids, and enhanced intestinal permeability. Both clinical and preclinical trials in patients with MS and animal models revealed that the administration of probiotic bacteria might improve cognitive, motor, and mental behaviors by modulation of GBA molecular pathways. According to the newest data, supplementation with probiotics may be associated with slower disability progression, reduced depressive symptoms, and improvements in general health in patients with MS. Herein, we give an overview of how probiotics supplementation may have a beneficial effect on the course of MS and its animal model. Hence, interference with the composition of the MS patient's intestinal microbiota may, in the future, be a grip point for the development of diagnostic tools and personalized microbiota-based adjuvant therapy.
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Melamed E, Palmer JL, Fonken C. Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis. Front Mol Neurosci 2022; 15:1019877. [PMID: 36407764 PMCID: PMC9672668 DOI: 10.3389/fnmol.2022.1019877] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 10/11/2022] [Indexed: 08/22/2023] Open
Abstract
Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.
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Affiliation(s)
- Esther Melamed
- Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, United States
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Bianchimano P, Britton GJ, Wallach DS, Smith EM, Cox LM, Liu S, Iwanowski K, Weiner HL, Faith JJ, Clemente JC, Tankou SK. Mining the microbiota to identify gut commensals modulating neuroinflammation in a mouse model of multiple sclerosis. MICROBIOME 2022; 10:174. [PMID: 36253847 PMCID: PMC9575236 DOI: 10.1186/s40168-022-01364-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 08/29/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease, hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotic effects are not understood. Furthermore, there is no consensus on the gut-derived bacterial strains that drive neuroinflammation in multiple sclerosis. RESULTS Here, we characterized the gut microbiome of untreated and vancomycin-treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE, and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut, and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found that Anaerotruncus colihominis ameliorates EAE, and this is associated with induction of RORγt+ regulatory T cells in the mesenteric lymph nodes. CONCLUSIONS We identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease. Video Abstract.
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Affiliation(s)
- Paola Bianchimano
- Department of Neurology, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
| | - Graham J Britton
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - David S Wallach
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Emma M Smith
- Department of Neurology, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
| | - Laura M Cox
- Ann Romney Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
| | - Shirong Liu
- Ann Romney Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
- Present address: Department of Medical Oncology, Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA
| | - Kacper Iwanowski
- Department of Neurology, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
| | - Howard L Weiner
- Ann Romney Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
| | - Jeremiah J Faith
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jose C Clemente
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Stephanie K Tankou
- Department of Neurology, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA.
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA.
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 5E 98th Street, New York, NY, 10029, USA.
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Rahimlou M, Nematollahi S, Husain D, Banaei-Jahromi N, Majdinasab N, Hosseini SA. Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Front Neurosci 2022; 16:901846. [PMID: 36203797 PMCID: PMC9531126 DOI: 10.3389/fnins.2022.901846] [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: 03/22/2022] [Accepted: 08/16/2022] [Indexed: 11/13/2022] Open
Abstract
Background Multiple sclerosis (MS) is a complex inflammatory disease in which demyelination occurs in the central nervous system affecting approximately 2.5 million people worldwide. Intestinal microbiome changes play an important role in the etiology of chronic diseases. Objective This study aimed to investigate the effect of probiotic supplementation on systemic inflammation in patients with MS. Methods A 12-week double-blind clinical trial study was designed and seventy patients with MS were randomly divided into two groups receiving probiotics and placebo. Patients in the intervention group received two capsules containing multi-strain probiotics daily and patients in the control group received the same amount of placebo. Factors associated with systemic inflammation were assessed at the beginning and end of the study. Results Sixty-five patients were included in the final analysis. There was no significant difference between the two groups in terms of baseline variables except for the duration of the disease (P > 0.05). At the end of the study, probiotic supplementation compared to the placebo caused a significant reduction in the serum levels of CRP (-0.93 ± 1.62 vs. 0.05 ± 1.74, P = 0.03), TNF-α (-2.09 ± 1.88 vs. 0.48 ± 2.53, P = 0.015) and IFN-γ (-13.18 ± 7.33 vs. -1.93 ± 5.99, P < 0.001). Also, we found a significant increase in the FOXP3 and TGF-β levels in the intervention group (P < 0.05). Conclusion The results of our study showed that supplementation with probiotics can have beneficial effects on serum levels of some factors associated with systemic inflammation. Clinical trial registration [http://www.irct.ir], identifier [IRCT20181210041 918N1].
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Affiliation(s)
- Mehran Rahimlou
- Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Nutrition, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Shima Nematollahi
- Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Durdana Husain
- Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nasrin Banaei-Jahromi
- Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nastaran Majdinasab
- Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Ahmad Hosseini
- Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Shahi SK, Yadav M, Ghimire S, Mangalam AK. Role of the gut microbiome in multiple sclerosis: From etiology to therapeutics. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 167:185-215. [PMID: 36427955 DOI: 10.1016/bs.irn.2022.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS that affects around one million people in the United States. Predisposition or protection from this disease is linked with both genetic and environmental factors. In recent years, gut microbiome has emerged as an important environmental factor in the pathobiology of MS. The gut microbiome supports various physiologic functions, including the development and maintenance of the host immune system, the perturbation of which is known as dysbiosis and has been linked with multiple diseases including MS. We and others have shown that people with MS (PwMS) have gut dysbiosis that is characterized by specific gut bacteria being enriched or depleted. Consequently, there is an emphasis on determining the mechanism(s) through which gut bacteria and/or their metabolites alter the course of MS through their ability to provide protection, predispose individuals, or promote disease progression. Improving our understanding of these mechanisms will allow us to harness the enormous potential of the gut microbiome as a diagnostic and/or therapeutic agent. In this chapter, we will discuss current advances in microbiome research in the context of MS, including a review of specific bacteria that are currently linked with this disease, potential mechanisms of disease pathogenesis, and the utility of microbiome-based therapy for PwMS.
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Affiliation(s)
- Shailesh K Shahi
- Department of Pathology, University of Iowa, Iowa City, IA, United States; Iowa City VA Health System, Iowa City, IA, United States
| | - Meeta Yadav
- Department of Pathology, University of Iowa, Iowa City, IA, United States; Iowa City VA Health System, Iowa City, IA, United States
| | - Sudeep Ghimire
- Department of Pathology, University of Iowa, Iowa City, IA, United States; Iowa City VA Health System, Iowa City, IA, United States
| | - Ashutosh K Mangalam
- Department of Pathology, University of Iowa, Iowa City, IA, United States; Iowa City VA Health System, Iowa City, IA, United States.
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Garabatos N, Santamaria P. Gut Microbial Antigenic Mimicry in Autoimmunity. Front Immunol 2022; 13:873607. [PMID: 35572569 PMCID: PMC9094498 DOI: 10.3389/fimmu.2022.873607] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota plays a major role in the developmental biology and homeostasis of cells belonging to the adaptive and innate arms of the immune system. Alterations in its composition, which are known to be regulated by both genetic and environmental factors, can either promote or suppress the pathogenic processes underlying the development of various autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and rheumatoid arthritis, to just name a few. Cross-recognition of gut microbial antigens by autoreactive T cells as well as gut microbe-driven alterations in the activation and homeostasis of effector and regulatory T cells have been implicated in this process. Here, we summarize our current understanding of the positive and negative associations between alterations in the composition of the gut microbiota and the development of various autoimmune disorders, with a special emphasis on antigenic mimicry.
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Affiliation(s)
- Nahir Garabatos
- Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Pere Santamaria
- Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Julia McFarlane Diabetes Research Centre (JMDRC), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Chen X, Zhang Y, Wang H, Liu L, Li W, Xie P. The regulatory effects of lactic acid on neuropsychiatric disorders. DISCOVER MENTAL HEALTH 2022; 2:8. [PMID: 37861858 PMCID: PMC10501010 DOI: 10.1007/s44192-022-00011-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 03/04/2022] [Indexed: 10/21/2023]
Abstract
Lactic acid is produced mainly in astrocytes in the brain and serves as a substance that supplies energy to neurons. In recent years, numerous studies identified the potential effects of lactic acid on the central nervous system and demonstrated its role in regulating brain function as an energy metabolism substrate or cellular signaling molecule. Both deficiency and accumulation of lactic acid cause neurological dysfunction, which further lead to the development of neuropsychiatric disorders, such as Major depressive disorder, Schizophrenia, Alzheimer's disease, and Multiple sclerosis. Although an association between lactic acid and neuropsychiatric disorders was reported in previous research, the underlying pathogenic mechanisms remain unclear. Therefore, an in-depth understanding of the molecular mechanisms by which lactic acid regulates brain function is of significance for the early diagnosis and prevention of neuropsychiatric disorders. In this review, we summarize evidence that is focused on the potential mechanisms of lactic acid as a signaling molecule involved in the pathogenesis of neuropsychiatric disorders and propose a new mechanism by which lactic acid regulates brain function and disease through the microbiota-gut-brain axis to offer new insight into the prevention and treatment of neuropsychiatric diseases.
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Affiliation(s)
- Xueyi Chen
- Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yangdong Zhang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Haiyang Wang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
- College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
| | - Lanxiang Liu
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
- Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China
| | - Wenwen Li
- Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Peng Xie
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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Michaličková D, Kübra Öztürk H, Hroudová J, Ľupták M, Kučera T, Hrnčíř T, Kutinová Canová N, Šíma M, Slanař O. Edaravone attenuates disease severity of experimental auto-immune encephalomyelitis and increases gene expression of Nrf2 and HO-1. Physiol Res 2022; 71:147-157. [PMID: 35043649 DOI: 10.33549/physiolres.934800] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondrial function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex II/III, reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.
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Affiliation(s)
- Danica Michaličková
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
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