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Vocca C, Abrego-Guandique DM, Cione E, Rania V, Marcianò G, Palleria C, Catarisano L, Colosimo M, La Cava G, Palumbo IM, De Sarro G, Ceccato T, Botti S, Cai T, Palmieri A, Gallelli L. Probiotics in the Management of Chronic Bacterial Prostatitis Patients: A Randomized, Double-Blind Trial to Evaluate a Possible Link Between Gut Microbiota Restoring and Symptom Relief. Microorganisms 2025; 13:130. [PMID: 39858898 PMCID: PMC11767496 DOI: 10.3390/microorganisms13010130] [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: 12/15/2024] [Accepted: 12/22/2024] [Indexed: 01/27/2025] Open
Abstract
Several studies have suggested that probiotics could play a role in the management of patients with chronic bacterial prostatitis (CBP). In this randomized, placebo-controlled clinical study, we evaluated the efficacy and safety of consumption of probiotics containing human Lactobacillus casei DG® as an add-on treatment in patients with clinical recurrences of CBP, through gut microbiota modification analysis. Enrolled patients with CBP were randomized to receive for 3 months probiotics containing human Lactobacillus casei DG® or placebo following 1 month treatment with ciprofloxacin. During the enrollment and follow-ups, urological examinations analyzed symptoms and quality of life, while microbiological tests analyzed gut and seminal microbiota. During the study, the development of adverse drug reactions was evaluated through the Naranjo scale. Twenty-four patients with CBP were recruited and treated for 3 months with placebo (n. 12) or with Lactobacillus casei DG® (n. 12). Lactobacillus casei DG® induced a significantly (p < 0.01) faster recovery of symptoms than placebo (2 days vs. 8 days) and an increased time free from symptoms (86 days vs. 42 days) without the occurrence of adverse events. In the probiotic group, the appearance of Lactobacilli after 30 days (T1) was higher vs. the placebo group, and a significant reduction in Corynebacterium, Peptoniphilus, Pseudomonas, Veillonella, Staphylococcus, and Streptococcus was also observed. These preliminary data suggest that in patients with CBP, the use of Lactobacillus casei DG after an antimicrobial treatment improves the days free of symptoms and the quality of life, without the development of adverse drug reactions.
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Affiliation(s)
- Cristina Vocca
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
| | - Diana Marisol Abrego-Guandique
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
| | - Erika Cione
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy;
| | - Vincenzo Rania
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
| | - Gianmarco Marcianò
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
| | - Caterina Palleria
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
| | - Luca Catarisano
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
| | - Manuela Colosimo
- Operative Unit of Microbiology and Virology, AOU Dulbecco, 88100 Catanzaro, Italy;
| | - Gregorio La Cava
- Urology Division Azienda Sanitaria Provinciale, Department of Primary Care, 88100 Catanzaro, Italy;
| | - Italo Michele Palumbo
- Department of Urology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy;
| | - Giovambattista De Sarro
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
- Research Center FAS@UMG, Department of Health Science, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Tommaso Ceccato
- Department of Urology, Santa Chiara Regional Hospital, 38123 Trento, Italy; (T.C.); (S.B.)
| | - Simone Botti
- Department of Urology, Santa Chiara Regional Hospital, 38123 Trento, Italy; (T.C.); (S.B.)
| | - Tommaso Cai
- Department of Urology, Santa Chiara Regional Hospital, 38123 Trento, Italy; (T.C.); (S.B.)
- Institute of Clinical Medicine, University of Oslo, 0313 Oslo, Norway
| | - Alessandro Palmieri
- Department of Urology, Federico II University of Naples, 80138 Naples, Italy;
| | - Luca Gallelli
- Operative Unit of Clinical Pharmacology and Pharmacovigilance, Department of Health Science, AOU Dulbecco, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (C.V.); (D.M.A.-G.); (V.R.); (G.M.); (C.P.); (L.C.); (G.D.S.); (L.G.)
- Research Center FAS@UMG, Department of Health Science, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
- Medifarmagen, University of Catanzaro and Renato Dulbecco Hospital, 88100 Catanzaro, Italy
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Zainab SR, Khan JZ, Rehman MU, Shah FA, Tipu MK. Effect of Bacillus clausii in attenuating symptoms of DSS-induced ulcerative colitis by modulating NFkB pathway and oxidative stress in mice. Clin Exp Pharmacol Physiol 2024; 51:e70004. [PMID: 39513300 DOI: 10.1111/1440-1681.70004] [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: 08/06/2024] [Revised: 09/24/2024] [Accepted: 10/14/2024] [Indexed: 11/15/2024]
Abstract
Ulcerative colitis (UC) is a condition characterized by inflammation and ulcer formation in the colon and rectum due to genetic and environmental factors. It is a common condition, with a global prevalence rate exceeding 0.3%. Current treatments have limited efficacy and can cause unwanted side effects, leading to a high recurrence rate and reduced quality of life for patients. This study suggests that Bacillus clausii has a beneficial role in reducing intestinal inflammation and relieving colitis symptoms in mice. The study aimed to examine B. clausii's potential to reduce the progression and pathogenesis of dextran sulphate sodium (DSS)-induced UC. Bacillus clausii was administered to mice as a pre-treatment, post-treatment and adjunct treatment with sulfasalazine for 14 days. The study found that B. clausii effectively reduced the severity of colitis in mice when used preventatively. Administering B. clausii after the onset of colitis also effectively alleviated symptoms. Combining B. clausii with standard sulfasalazine as adjunct therapy was more effective in reducing intestinal inflammation than using a single therapy alone. B. clausii has shown the potential to prevent colon damage and decrease the likelihood and severity of the disease. Immunohistochemistry results revealed a decrease in the expression of pro-inflammatory cytokines such as IL-1β, TNF-α and NFkB in colon tissue. Additionally, mice that received B. clausii showed a significant increase in anti-oxidant levels and improved haematological markers. In conclusion, it must be emphasized that B. clausii possesses the potential to alleviate the symptoms of UC.
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Affiliation(s)
- Syeda Rida Zainab
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Jehan Zeb Khan
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Mujeeb Ur Rehman
- Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar, Pakistan
| | - Fawad Ali Shah
- Department of Pharmacology and Toxicology, College of Pharmacy Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Muhammad Khalid Tipu
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
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García-Gamboa R, Díaz-Torres O, Gradilla-Hernández MS, Pérez-Brocal V, Moya A, González-Avila M. Gut Bacterial Composition and Nutritional Implications in Mexican and Spanish Individuals with Inflammatory Bowel Disease Compared to Healthy Controls. Int J Mol Sci 2024; 25:11887. [PMID: 39595956 PMCID: PMC11593679 DOI: 10.3390/ijms252211887] [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: 09/04/2024] [Revised: 10/19/2024] [Accepted: 10/31/2024] [Indexed: 11/28/2024] Open
Abstract
The intestinal microbiota plays a key role in the pathogenesis of inflammatory bowel disease (IBD), with its composition varying based on geographic location and dietary factors. This study was performed to examine and compare the bacterial composition of the gut microbiota in Mexican and Spanish individuals with IBD and healthy controls, while also considering the nutritional aspects. This study involved 79 individuals with IBD and healthy controls from Mexico and Spain. The fecal microbiota composition was analyzed using 16S rRNA gene sequencing, and the dietary intake and anthropometric measurements were collected. Alpha diversity analysis revealed a lower Chao1 index of the bacterial genera in the IBD groups. Beta diversity analysis showed significant differences in the bacterial composition, suggesting inter-individual variability within the healthy and IBD groups. Additionally, the relative abundance of the bacterial genera varied across the four groups. Faecalibacterium was more abundant in the IBD groups; Prevotella was found exclusively in the Mexican groups, and Akkermansia was found only in the Spanish groups. Akkermansia was positively correlated with meat and protein intake, Prevotella with lean mass, and Bacteroides with calorie intake. These findings highlight the importance of considering geographic and nutritional factors in future research on the gut microbiome's role in IBD pathogenesis.
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Affiliation(s)
- Ricardo García-Gamboa
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Av. General Ramon Corona 2514, Nuevo Mexico, Zapopan 45138, Jalisco, Mexico
| | - Osiris Díaz-Torres
- Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Laboratorio de Sostenibilidad y Cambio Climático, Av. General Ramon Corona 2514, Zapopan 45138, Jalisco, Mexico
| | - Misael Sebastián Gradilla-Hernández
- Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Laboratorio de Sostenibilidad y Cambio Climático, Av. General Ramon Corona 2514, Zapopan 45138, Jalisco, Mexico
| | - Vicente Pérez-Brocal
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Av. de Cataluña 21, 46020 València, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERSEP), c/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain
| | - Andrés Moya
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Av. de Cataluña 21, 46020 València, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERSEP), c/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain
- Integrative Systems Biology Institute (I2SysBio), Universitat de València and Consejo Superior de Investigaciones Científicas (CSIC), c/Catedrático José Beltrán 2, 46980 Paterna, València, Spain
| | - Marisela González-Avila
- Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A.C., Av. Normalistas No. 800, col Colinas de la Normal, Guadalajara 44270, Jalisco, Mexico
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Ren Q, He C, Sun Y, Gao X, Zhou Y, Qin T, Zhang Z, Wang X, Wang J, Wei S, Wang F. Asiaticoside improves depressive-like behavior in mice with chronic unpredictable mild stress through modulation of the gut microbiota. Front Pharmacol 2024; 15:1461873. [PMID: 39494347 PMCID: PMC11527651 DOI: 10.3389/fphar.2024.1461873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/02/2024] [Indexed: 11/05/2024] Open
Abstract
Background Asiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression. Methods Behavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA. Results This study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic-pituitary-adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis. Conclusions These results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model.
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Affiliation(s)
- Qingyi Ren
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Chenxi He
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yuhong Sun
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xiaowei Gao
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yan Zhou
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Tao Qin
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhuo Zhang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xiaodong Wang
- Department of Hepatobiliary Disease, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Jun Wang
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Siping Wei
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University), Guilin, China
| | - Fang Wang
- Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, China
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
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Qiao Y, Tang X, Liu Z, Ocansey DKW, Zhou M, Shang A, Mao F. Therapeutic Prospects of Mesenchymal Stem Cell and Their Derived Exosomes in the Regulation of the Gut Microbiota in Inflammatory Bowel Disease. Pharmaceuticals (Basel) 2024; 17:607. [PMID: 38794176 PMCID: PMC11124012 DOI: 10.3390/ph17050607] [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: 04/04/2024] [Revised: 05/05/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.
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Affiliation(s)
- Yaru Qiao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, China; (Y.Q.); (Z.L.); (D.K.W.O.); (M.Z.)
- Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University, Lianyungang 222006, China;
| | - Xiaohua Tang
- The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang 212300, China;
| | - Ziyue Liu
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, China; (Y.Q.); (Z.L.); (D.K.W.O.); (M.Z.)
| | - Dickson Kofi Wiredu Ocansey
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, China; (Y.Q.); (Z.L.); (D.K.W.O.); (M.Z.)
- Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast CC0959347, Ghana
| | - Mengjiao Zhou
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, China; (Y.Q.); (Z.L.); (D.K.W.O.); (M.Z.)
| | - Anquan Shang
- Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University, Lianyungang 222006, China;
| | - Fei Mao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, China; (Y.Q.); (Z.L.); (D.K.W.O.); (M.Z.)
- Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University, Lianyungang 222006, China;
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Crouch LI, Rodrigues CS, Bakshani CR, Tavares-Gomes L, Gaifem J, Pinho SS. The role of glycans in health and disease: Regulators of the interaction between gut microbiota and host immune system. Semin Immunol 2024; 73:101891. [PMID: 39388764 DOI: 10.1016/j.smim.2024.101891] [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: 08/02/2024] [Revised: 10/03/2024] [Accepted: 10/03/2024] [Indexed: 10/12/2024]
Abstract
The human gut microbiota is home to a diverse collection of microorganisms that has co-evolved with the host immune system in which host-microbiota interactions are essential to preserve health and homeostasis. Evidence suggests that the perturbation of this symbiotic host-microbiome relationship contributes to the onset of major diseases such as chronic inflammatory diseases including Inflammatory Bowel Disease. The host glycocalyx (repertoire of glycans/sugar-chains at the surface of gut mucosa) constitutes a major biological and physical interface between the intestinal mucosa and microorganisms, as well as with the host immune system. Glycans are an essential niche for microbiota colonization and thus an important modulator of host-microorganism interactions both in homeostasis and in disease. In this review, we discuss the role of gut mucosa glycome as an instrumental pathway that regulates host-microbiome interactions in homeostasis but also in health to inflammation transition. We also discuss the power of mucosa glycosylation remodelling as an attractive preventive and therapeutic strategy to preserve gut homeostasis.
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Affiliation(s)
- Lucy I Crouch
- Department of Microbes, Infection and Microbiomes, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK.
| | - Cláudia S Rodrigues
- i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
| | - Cassie R Bakshani
- Department of Microbes, Infection and Microbiomes, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK
| | - Leticia Tavares-Gomes
- i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Joana Gaifem
- i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Salomé S Pinho
- i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal.
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Li C, Peng K, Xiao S, Long Y, Yu Q. The role of Lactobacillus in inflammatory bowel disease: from actualities to prospects. Cell Death Discov 2023; 9:361. [PMID: 37773196 PMCID: PMC10541886 DOI: 10.1038/s41420-023-01666-w] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 09/18/2023] [Accepted: 09/22/2023] [Indexed: 10/01/2023] Open
Abstract
Inflammatory Bowel Disease (IBD), a chronic nonspecific intestinal inflammatory disease, is comprised of Ulcerative Colitis (UC) and Crohn's Disease (CD). IBD is closely related to a systemic inflammatory reaction and affects the progression of many intestinal and extraintestinal diseases. As one of the representative bacteria for probiotic-assisted therapy in IBD, multiple strains of Lactobacillus have been proven to alleviate intestinal damage and strengthen the intestinal immunological barrier, epithelial cell barrier, and mucus barrier. Lactobacillus also spares no effort in the alleviation of IBD-related diseases such as Colitis-associated Colorectal cancer (CAC), Alzheimer's Disease (AD), Depression, Anxiety, Autoimmune Hepatitis (AIH), and so on via gut-brain axis and gut-liver axis. This article aims to discuss the role of Lactobacillus in IBD and IBD-related diseases, including its underlying mechanisms and related curative strategies from the present to the future.
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Affiliation(s)
- Congxin Li
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Kaixin Peng
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Siqi Xiao
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Yuanyuan Long
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Qin Yu
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
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Hashemi SF, Khorramdelazad H. The cryptic role of CXCL17/CXCR8 axis in the pathogenesis of cancers: a review of the latest evidence. J Cell Commun Signal 2023; 17:409-422. [PMID: 36352331 PMCID: PMC10409701 DOI: 10.1007/s12079-022-00699-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/17/2022] [Accepted: 09/12/2022] [Indexed: 11/10/2022] Open
Abstract
Chemokines are immune system mediators that mediate various activities and play a role in the pathogenesis of several cancers. Among these chemokines, C-X-C motif chemokine 17 (CXCL-17) is a relatively novel molecule produced along the airway epithelium in physiological and pathological conditions, and evidence shows that it plays a homeostatic role in most cases. CXCL17 has a protective role in some cancers and a pathological role in others, such as liver and lung cancer. This chemokine, along with its possible receptor termed G protein-coupled receptor 35 (GPR35) or CXCR8, are involved in recruiting myeloid cells, regulating angiogenesis, defending against pathogenic microorganisms, and numerous other mechanisms. Considering the few studies that have been performed on the dual role of CXCL17 in human malignancies, this review has investigated the possible pro-tumor and anti-tumor roles of this chemokine, as well as future treatment options in cancer therapy.
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Affiliation(s)
| | - Hossein Khorramdelazad
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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ElFeky DS, Awad AR, Shamseldeen AM, Mowafy HL, Hosny SA. Comparing the therapeutic potentials of Lactobacillus johnsonii vs. Lactobacillus acidophilus against vulvovaginal candidiasis in female rats: an in vivo study. Front Microbiol 2023; 14:1222503. [PMID: 37529322 PMCID: PMC10388188 DOI: 10.3389/fmicb.2023.1222503] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 06/26/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Vulvovaginal candidiasis (VVC) is a highly prevalent illness affecting women globally. Lactobacilli, which make up the majority of healthy vaginal microbiota (VMB), serve as a powerful barrier against infections. Probiotic therapy has been recommended for the treatment or prevention of VVC. AIM OF WORK To compare the in vivo therapeutic effects of Lactobacillus johnsonii (B-2178) vs. Lactobacillus acidophilus (LA-5®) on VVC in a rat model, particularly highlighting the immune response of the host vaginal epithelium. METHODS In total, 30 female Sprague-Dawley rats were divided into 5 groups; Group 1: no intervention, Group 2: ovariectomy group, while animals in Groups 3-5 were subjected to ovariectomy and an intravaginal inoculation of Candida albicans (C. albicans) to establish VVC. The animals in Groups 4 and 5 received intravaginal lactobacilli treatment with L. acidophilus (LA-5®) and L. johnsonii (B-2178) strains, respectively, for 7 days. C. albicans load was measured in a vaginal lavage 1, 3, and 7 days after the stoppage of the treatment. Histological, morphometric, and immunohistochemical studies of the vaginal tissues were done. IFN-γ, IL-4, and IL-17 were measured in the vaginal tissue. RESULTS Both L. johnsonii and L. acidophilus significantly reduced C. albicans vaginal load (250 ± 77.46 and 133.33 ± 40.82 CFU/mL) compared to the count before treatment in both groups (4,850 ± 1419.51 and 4966.67 ± 852.45 CFU/mL) even after 7 days of stoppage of lactobacilli treatment. A statistically significant reduction of the pro-inflammatory cytokines IL-17 and IFN-γ was reported in both treated groups compared to the infected untreated group. L. johnsonii has a significant effect on the reduction of hyphae formation of C. albicans as well as the nuclear factor kappa B (NF-κB) immunostaining density of vaginal tissue compared to L. acidophilus. Moreover, treatment with L. johnsonii significantly minimized the epithelium damage triggered by C. albicans infection and restored normal vaginal architecture as evidenced by the histologic and morphometric studies when compared to L. acidophilus. CONCLUSION Through maintaining an immune tolerant state in the vaginal epithelium and ameliorating the undesirable uncontrolled inflammatory response in the vaginal tissue, L. johnsonii (B-2178) has the potential to be utilized alone or in combination with other lactobacilli species in probiotic clinical trials to treat or prevent VVC.
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Affiliation(s)
- Dalia Saad ElFeky
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Alaa Reda Awad
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Asmaa Mohammed Shamseldeen
- Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Physiology, Faculty of Medicine, October 6 University, Giza, Egypt
| | - Hagar Lotfy Mowafy
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Sara Adel Hosny
- Histology Department, Faculty of Medicine, Cairo University, Giza, Egypt
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10
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Li Q, Zheng T, Ding H, Chen J, Li B, Zhang Q, Yang S, Zhang S, Guan W. Exploring the Benefits of Probiotics in Gut Inflammation and Diarrhea-From an Antioxidant Perspective. Antioxidants (Basel) 2023; 12:1342. [PMID: 37507882 PMCID: PMC10376667 DOI: 10.3390/antiox12071342] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/17/2023] [Accepted: 06/19/2023] [Indexed: 07/30/2023] Open
Abstract
Inflammatory bowel disease (IBD), characterized by an abnormal immune response, includes two distinct types: Crohn's disease (CD) and ulcerative colitis (UC). Extensive research has revealed that the pathogeny of IBD encompasses genetic factors, environmental factors, immune dysfunction, dysbiosis, and lifestyle choices. Furthermore, patients with IBD exhibit both local and systemic oxidative damage caused by the excessive presence of reactive oxygen species. This oxidative damage exacerbates immune response imbalances, intestinal mucosal damage, and dysbiosis in IBD patients. Meanwhile, the weaning period represents a crucial phase for pigs, during which they experience pronounced intestinal immune and inflammatory responses, leading to severe diarrhea and increased mortality rates. Pigs are highly similar to humans in terms of physiology and anatomy, making them a potential choice for simulating human IBD. Although the exact mechanism behind IBD and post-weaning diarrhea remains unclear, the oxidative damage, in its progression and pathogenesis, is well acknowledged. Besides conventional anti-inflammatory drugs, certain probiotics, particularly Lactobacillus and Bifidobacteria strains, have been found to possess antioxidant properties. These include the scavenging of reactive oxygen species, chelating metal ions to inhibit the Fenton reaction, and the regulation of host antioxidant enzymes. Consequently, numerous studies in the last two decades have committed to exploring the role of probiotics in alleviating IBD. Here, we sequentially discuss the oxidative damage in IBD and post-weaning diarrhea pathogenesis, the negative consequences of oxidative stress on IBD, the effectiveness of probiotics in IBD treatment, the application of probiotics in weaned piglets, and the potential antioxidant mechanisms of probiotics.
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Affiliation(s)
- Qihui Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Tenghui Zheng
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Hanting Ding
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Jiaming Chen
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Baofeng Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Qianzi Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Siwang Yang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Shihai Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
- College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China
- Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China
| | - Wutai Guan
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
- College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China
- Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China
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11
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Airola C, Severino A, Porcari S, Fusco W, Mullish BH, Gasbarrini A, Cammarota G, Ponziani FR, Ianiro G. Future Modulation of Gut Microbiota: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy. Antibiotics (Basel) 2023; 12:antibiotics12050868. [PMID: 37237771 DOI: 10.3390/antibiotics12050868] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/03/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.
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Affiliation(s)
- Carlo Airola
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Andrea Severino
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - William Fusco
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London W2 1NY, UK
- Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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12
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Pal R, Athamneh AI, Deshpande R, Ramirez JAR, Adu KT, Muthuirulan P, Pawar S, Biazzo M, Apidianakis Y, Sundekilde UK, de la Fuente-Nunez C, Martens MG, Tegos GP, Seleem MN. Probiotics: insights and new opportunities for Clostridioides difficile intervention. Crit Rev Microbiol 2023; 49:414-434. [PMID: 35574602 PMCID: PMC9743071 DOI: 10.1080/1040841x.2022.2072705] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 04/17/2022] [Accepted: 04/28/2022] [Indexed: 02/08/2023]
Abstract
Clostridioides difficile infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen C. difficile. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commensal microorganisms, or probiotics, is one of the most investigated non-antibiotic therapeutic options to balance gastrointestinal (GI) microbiota and subsequently tackle dysbiosis. In this review, we will discuss major commensal probiotic strains that have the potential to prevent and/or treat CDI and its recurrence, reassess the efficacy of probiotics supplementation as a CDI intervention, delve into lessons learned from probiotic modulation of the immune system, explore avenues like genome-scale metabolic network reconstructions, genome sequencing, and multi-omics to identify novel strains and understand their functionality, and discuss the current regulatory framework, challenges, and future directions.
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Affiliation(s)
- Rusha Pal
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA
| | - Ahmad I.M. Athamneh
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
| | | | - Jose A. R Ramirez
- ProbioWorld Consulting Group, James Cook University, 4811, Queensland, Australia
| | - Kayode T. Adu
- ProbioWorld Consulting Group, James Cook University, 4811, Queensland, Australia
- Cann Group, Walter and Eliza Hall Institute, La Trobe University, Victoria 3083, Australia
| | | | - Shrikant Pawar
- The Anlyan Center Yale Center for Genomic Analysis, Yale School of Medicine, New Haven CT USA
| | - Manuele Biazzo
- The Bioarte Ltd Laboratories at Life Science Park, San Gwann, Malta
| | | | | | - Cesar de la Fuente-Nunez
- Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Mark G. Martens
- Reading Hospital, Tower Health, West Reading, PA 19611, USA
- Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - George P. Tegos
- Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - Mohamed N. Seleem
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
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13
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Cheng R, Zhu H, Sun Y, Hang T, Zhang M. The modified outer membrane protein Amuc_1100 of Akkermansia muciniphila improves chronic stress-induced anxiety and depression-like behavior in mice. Food Funct 2022; 13:10748-10758. [PMID: 36178497 DOI: 10.1039/d2fo01198k] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Akkermansia muciniphila is a next-generation probiotic. The interaction between outer membrane protein Amuc_1100 of A. muciniphila and toll-like receptor 2 (TLR2) in intestinal epithelial cells influences the level of intestinal 5-hydroxytryptamine (5-HT). Amuc_1100Δ80 is a truncated form of Amuc_1100 lacking the first 80 N-terminal amino acids and has a higher affinity for TLR2 than the wild-type protein. Here, we report that Amuc_1100Δ80 could significantly reduce anxiety and depression-like behavior of mice when they were exposed to chronic unpredictable mild stress (CUMS). The experimental results of the rat insulinoma cell line RIN-14B showed that Amuc_1100Δ80 also induced a significantly higher upregulation of tryptophan hydroxylase 1 (Tph1), a rate-limiting enzyme of intestinal 5-HT synthesis. The imbalance of the gut microflora could be diminished when CUMS mice were fed with Amuc_1100Δ80. These results reveal that Amuc_1100Δ80 could affect the 5-HT level and the downstream 5-HTR1A-CREB-BDNF signal pathway via interacting with TLR2 and by altering the gut microbial composition. In parallel, the downregulation exerted by Amuc_1100Δ80 on the inflammation and hyperactivated HPA axis was closely related to the improvement of depression-like symptoms in CUMS mice. This study not only provides new insights into the antidepressant effect of A. muciniphila and its outer membrane protein Amuc_1100 but also identifies new potential targets and pathways in the gut for future research and the development of antidepressant drugs.
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Affiliation(s)
- Rongrong Cheng
- School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China
| | - Haiyan Zhu
- School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China
| | - Yan Sun
- School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China
| | - Tianrong Hang
- School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China
| | - Min Zhang
- School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China. .,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China
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14
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Viswanath K, Hayes M, Avni D. Inflammatory bowel disease - A peek into the bacterial community shift and algae-based ‘biotic’ approach to combat the disease. Trends Food Sci Technol 2022. [DOI: 10.1016/j.tifs.2022.09.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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15
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The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs. Int J Mol Sci 2022; 23:ijms23137151. [PMID: 35806156 PMCID: PMC9266754 DOI: 10.3390/ijms23137151] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 06/23/2022] [Accepted: 06/25/2022] [Indexed: 02/06/2023] Open
Abstract
CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary glands, stomach, liver, pancreas, intestines, and kidneys). We focus on the importance of CXCL1 on implantation and placentation as well as on human pluripotent stem cells. We also show the significance of CXCL1 in selected diseases of the abdominal organs, including the gastrointestinal tract and oral cavity (periodontal diseases, periodontitis, Sjögren syndrome, Helicobacter pylori infection, diabetes, liver cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), HBV and HCV infection, liver ischemia and reperfusion injury, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), obesity and overweight, kidney transplantation and ischemic-reperfusion injury, endometriosis and adenomyosis).
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16
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Hitch TCA, Hall LJ, Walsh SK, Leventhal GE, Slack E, de Wouters T, Walter J, Clavel T. Microbiome-based interventions to modulate gut ecology and the immune system. Mucosal Immunol 2022; 15:1095-1113. [PMID: 36180583 PMCID: PMC9705255 DOI: 10.1038/s41385-022-00564-1] [Citation(s) in RCA: 85] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 02/04/2023]
Abstract
The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.
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Affiliation(s)
- Thomas C A Hitch
- Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Lindsay J Hall
- Gut Microbes & Health, Quadram Institute Biosciences, Norwich, UK
- Intestinal Microbiome, School of Life Sciences, ZIEL-Institute for Food & Health, Technical University of Munich, Freising, Germany
- Norwich Medical School, University of East Anglia, Norwich, UK
| | - Sarah Kate Walsh
- School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
- APC Microbiome Ireland, School of Microbiology and Department of Medicine, University College Cork, Cork, Ireland
| | | | - Emma Slack
- Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland
| | | | - Jens Walter
- APC Microbiome Ireland, School of Microbiology and Department of Medicine, University College Cork, Cork, Ireland
| | - Thomas Clavel
- Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany.
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17
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Eltokhi A, Sommer IE. A Reciprocal Link Between Gut Microbiota, Inflammation and Depression: A Place for Probiotics? Front Neurosci 2022; 16:852506. [PMID: 35546876 PMCID: PMC9081810 DOI: 10.3389/fnins.2022.852506] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Depression is a severe mental disorder that places a significant economic burden on public health. The reciprocal link between the trillions of bacteria in the gut, the microbiota, and depression is a controversial topic in neuroscience research and has drawn the attention of public interest and press coverage in recent years. Mounting pieces of evidence shed light on the role of the gut microbiota in depression, which is suggested to involve immune, endocrine, and neural pathways that are the main components of the microbiota-gut-brain axis. The gut microbiota play major roles in brain development and physiology and ultimately behavior. The bidirectional communication between the gut microbiota and brain function has been extensively explored in animal models of depression and clinical research in humans. Certain gut microbiota strains have been associated with the pathophysiology of depression. Therefore, oral intake of probiotics, the beneficial living bacteria and yeast, may represent a therapeutic approach for depression treatment. In this review, we summarize the findings describing the possible links between the gut microbiota and depression, focusing mainly on the inflammatory markers and sex hormones. By discussing preclinical and clinical studies on probiotics as a supplementary therapy for depression, we suggest that probiotics may be beneficial in alleviating depressive symptoms, possibly through immune modulation. Still, further comprehensive studies are required to draw a more solid conclusion regarding the efficacy of probiotics and their mechanisms of action.
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Affiliation(s)
- Ahmed Eltokhi
- Department of Pharmacology, University of Washington, Seattle, WA, United States
| | - Iris E Sommer
- Department of Biomedical Sciences of Cells & Systems, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
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18
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Han Y, Jia Z, Shi J, Wang W, He K. The active lung microbiota landscape of COVID-19 patients through the metatranscriptome data analysis. BIOIMPACTS : BI 2022; 12:139-146. [PMID: 35411293 PMCID: PMC8905590 DOI: 10.34172/bi.2021.23378] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 10/30/2020] [Accepted: 11/14/2020] [Indexed: 12/12/2022]
Abstract
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Introduction: With the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the interaction between the host and SARS-CoV-2 was widely studied. However, it is unclear whether and how SARS-CoV-2 infection affects lung microflora, which contribute to COVID-19 complications.
Methods: Here, we analyzed the metatranscriptomic data of bronchoalveolar lavage fluid (BALF) of 19 COVID-19 patients and 23 healthy controls from 6 independent projects and detailed the active microbiota landscape in both healthy individuals and COVID-19 patients.
Results: The infection of SARS-CoV-2 could deeply change the lung microbiota, evidenced by the α-diversity, β-diversity, and species composition analysis based on bacterial microbiota and virome. Pathogens (e.g., Klebsiella oxytoca causing pneumonia as well), immunomodulatory probiotics (e.g., lactic acid bacteria and Faecalibacterium prausnitzii, a butyrate producer), and Tobacco mosaic virus (TMV) were enriched in the COVID-19 group, suggesting a severe microbiota dysbiosis. The significant correlation between Rothia mucilaginosa, TMV, and SARS-CoV-2 revealed drastic inflammatory battles between the host, SARS-CoV-2, and other microbes in the lungs. Notably, TMV only existed in the COVID-19 group, while human respirovirus 3 (HRV 3) only existed in the healthy group. Our study provides insights into the active microbiota in the lungs of COVID-19 patients and would contribute to the understanding of the infection mechanism of SARS-CoV-2 and the treatment of the disease and complications.
Conclusion: SARS-COV-2 infection deeply altered the lung microbiota of COVID-19 patients. The enrichment of several other pathogens, immunomodulatory probiotics (lactic acid or butyrate producers), and TMV in the COVID-19 group suggests a complex and active lung microbiota disorder.
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Affiliation(s)
- Yang Han
- Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China.,Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
| | - Zhilong Jia
- Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China.,Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
| | - Jinlong Shi
- Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China.,Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
| | - Weidong Wang
- Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China.,Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
| | - Kunlun He
- Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China.,Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, China
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Zhang W, Tan B, Deng J, Yang Q, Chi S, Pang A, Xin Y, Liu Y, Zhang H. PRR-Mediated Immune Response and Intestinal Flora Profile in Soybean Meal-Induced Enteritis of Pearl Gentian Groupers, Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂. Front Immunol 2022; 13:814479. [PMID: 35296073 PMCID: PMC8919722 DOI: 10.3389/fimmu.2022.814479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/25/2022] [Indexed: 11/22/2022] Open
Abstract
Pattern recognition receptors (PRRs) can recognize microbial-specific pathogen-associated molecular patterns, initiate signal cascade transduction, activate the expressions of host immunity and proinflammatory genes, and, ultimately, trigger an immune response against identified pathogens. The present study focused on two outcomes of feeding pearl gentian groupers with high levels of soybean meal (SBM): (1) growth performance and (2) the intestinal environment, including tissue structure, flora profile, and immune responses. Some 720 groupers were randomly divided into three groups (n = 4): (1) controls, fed a 50% fish meal feed (FM), (2) with 20% of the FM substituted with SBM (SBM20), and (3) 40% of the FM substituted with SBM (SBM40). The fish were fed these iso-nitrogenous and iso-lipidic diets for 10 weeks. They were kept in containers with 1 m3 of water under natural light and temperature levels. The experimental results demonstrate that the SBM diets significantly degraded growth performance and intestinal physiology. Typical enteritis characteristics and immune fluctuations appeared, as reflected by the enzyme activities of total superoxide dismutase and lysozyme, and the contents of immunoglobulin M, complement 3, and complement 4. 16SrDNA high-throughput sequencing showed that the intestinal flora was significantly affected, with the abundance of harmful bacteria, such as Vibrio and Streptococcus, increasing with dietary SBM level. Based on "3 + 2" full-length transcriptome sequencing, three triggered PRRs were found in the intestine: the RIG-like receptor, NOD-like receptor, and Toll-like receptor signaling pathways. The intestinal flora variations were significantly correlated with the activation of the three PRR signaling pathways by canonical correlation analysis. These culminated in the transcriptome activation of NF-κB, IRFs, and costimulatory molecules, ultimately promoting the expressions of proinflammatory cytokines, interferons (IFNs), chemokines, and other molecules vital to the innate and/or adaptive immune responses. This study provides new information for diagnosing and preventing SBMIE in aquaculture fish.
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Affiliation(s)
- Wei Zhang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Beiping Tan
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Junming Deng
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Qihui Yang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Shuyan Chi
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Aobo Pang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Yu Xin
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Yu Liu
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Haitao Zhang
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
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Hu Y, Ye Z, Wu M, She Y, Li L, Xu Y, Qin K, Hu Z, Yang M, Lu F, Ye Q. The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies. Front Med (Lausanne) 2021; 8:766126. [PMID: 34966755 PMCID: PMC8710685 DOI: 10.3389/fmed.2021.766126] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022] Open
Abstract
Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.
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Affiliation(s)
- Yu Hu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhen Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mingquan Wu
- Department of Pharmacy, Sichuan Provincial Orthopedic Hospital, Chengdu, China
| | - Yingqi She
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Linzhen Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yujie Xu
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Kaihua Qin
- Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhipeng Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Maoyi Yang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fating Lu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiaobo Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Song X, Pi S, Gao Y, Zhou F, Yan S, Chen Y, Qiao L, Dou X, Shao D, Xu C. The Role of Vasoactive Intestinal Peptide and Mast Cells in the Regulatory Effect of Lactobacillus casei ATCC 393 on Intestinal Mucosal Immune Barrier. Front Immunol 2021; 12:723173. [PMID: 34899686 PMCID: PMC8657605 DOI: 10.3389/fimmu.2021.723173] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 11/09/2021] [Indexed: 01/07/2023] Open
Abstract
Vasoactive intestinal peptide (VIP) plays an important role in the neuro-endocrine-immune system. Mast cells (MCs) are important immune effector cells. This study was conducted to investigate the protective effect of L. casei ATCC 393 on Enterotoxigenic Escherichia coli (ETEC) K88-induced intestinal mucosal immune barrier injury and its association with VIP/MC signaling by in vitro experiments in cultures of porcine mucosal mast cells (PMMCs) and in vivo experiments using VIP receptor antagonist (aVIP) drug. The results showed that compared with the ETEC K88 and lipopolysaccharides (LPS)-induced model groups, VIP pretreatment significantly inhibited the activation of MCs and the release of β-hexosaminidase (β-hex), histamine and tryptase. Pretreatment with aVIP abolished the protective effect of L. casei ATCC 393 on ETEC K88-induced intestinal mucosal immune barrier dysfunction in C57BL/6 mice. Also, with the blocking of VIP signal transduction, the ETEC K88 infection increased serum inflammatory cytokines, and the numbers of degranulated MCs in ileum, which were decreased by administration of L. casei ATCC 393. In addition, VIP mediated the regulatory effect of L. casei ATCC 393 on intestinal microbiota in mice. These findings suggested that VIP may mediate the protective effect of L.casei ATCC 393 on intestinal mucosal immune barrier dysfunction via MCs.
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Affiliation(s)
- Xiaofan Song
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Shanyao Pi
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Yueming Gao
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Fengxia Zhou
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Shuqi Yan
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Yue Chen
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Lei Qiao
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Xina Dou
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Dongyan Shao
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Chunlan Xu
- The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
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Lee Y, Kamada N, Moon JJ. Oral nanomedicine for modulating immunity, intestinal barrier functions, and gut microbiome. Adv Drug Deliv Rev 2021; 179:114021. [PMID: 34710529 PMCID: PMC8665886 DOI: 10.1016/j.addr.2021.114021] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/17/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022]
Abstract
The gastrointestinal tract (GIT) affects not only local diseases in the GIT but also various systemic diseases. Factors that can affect the health and disease of both GIT and the human body include 1) the mucosal immune system composed of the gut-associated lymphoid tissues and the lamina propria, 2) the intestinal barrier composed of mucus and intestinal epithelium, and 3) the gut microbiota. Selective delivery of drugs, including antigens, immune-modulators, intestinal barrier enhancers, and gut-microbiome manipulators, has shown promising results for oral vaccines, immune tolerance, treatment of inflammatory bowel diseases, and other systemic diseases, including cancer. However, physicochemical and biological barriers of the GIT present significant challenges for successful translation. With the advances of novel nanomaterials, oral nanomedicine has emerged as an attractive option to not only overcome these barriers but also to selectively deliver drugs to the target sites in GIT. In this review, we discuss the GIT factors and physicochemical and biological barriers in the GIT. Furthermore, we present the recent progress of oral nanomedicine for oral vaccines, immune tolerance, and anti-inflammation therapies. We also discuss recent advances in oral nanomedicine designed to fortify the intestinal barrier functions and modulate the gut microbiota and microbial metabolites. Finally, we opine about the future directions of oral nano-immunotherapy.
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Affiliation(s)
- Yonghyun Lee
- Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 03760, South Korea; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea.
| | - Nobuhiko Kamada
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA
| | - James J Moon
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109 USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109 USA.
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Larussa T, Abenavoli L, Fabiano G, Mancuso MA, Polimeni N, Dumitrascu DL, Luzza F. Gut microbiota in inflammatory bowel disease: a target for therapy not to be missed. Minerva Gastroenterol (Torino) 2021; 67:357-368. [PMID: 35040302 DOI: 10.23736/s2724-5985.21.02907-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In the last years, the gut microbiota achieved great importance, since several studies demonstrated its correlation with the immune system and with the maintenance of intestinal homeostasis, as well as with the regulation of the integrity of the epithelium and the intestinal motility. An imbalance in microbial species promotes a dysbiosis, which has been associated with chronic diseases such as metabolic syndrome, inflammatory diseases, and some behavior disorders. The association with gut microbiota and dysbiosis has been demonstrated mostly in inflammatory bowel disease (IBD). Several studies investigated the application of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation in the treatment strategies for IBD. In this review, we discuss the recent findings on the potential role of the gut microbiota manipulation, with particular attention to bacterial microbiota, which could be implicated for a successful IBD therapeutic approach.
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Affiliation(s)
- Tiziana Larussa
- Department of Health Sciences, Magna Græcia University, Catanzaro, Italy -
| | - Ludovico Abenavoli
- Department of Health Sciences, Magna Græcia University, Catanzaro, Italy
| | - Giulia Fabiano
- Department of Health Sciences, Magna Græcia University, Catanzaro, Italy
| | - Maria A Mancuso
- Department of Health Sciences, Magna Græcia University, Catanzaro, Italy
| | - Natale Polimeni
- Digestive Endoscopy Service, Casa di Cura Policlinico Madonna della Consolazione, Reggio Calabria, Italy
| | - Dan L Dumitrascu
- Second Medical Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Francesco Luzza
- Department of Health Sciences, Magna Græcia University, Catanzaro, Italy
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Qiu K, Huang Y, Anselmo AC. Polymer and Crosslinker Content Influences Performance of Encapsulated Live Biotherapeutic Products. Cell Mol Bioeng 2021; 14:487-499. [PMID: 34777606 PMCID: PMC8548438 DOI: 10.1007/s12195-021-00674-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/27/2021] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Live biotherapeutic products (LBPs), or therapeutic microbes, are an emerging therapeutic modality for prevention and treatment of gastrointestinal diseases. Since LBPs are living, they are uniquely sensitive to external stresses (e.g., oxygen, acid) encountered during manufacturing, storage, and delivery. Here, we systematically evaluate how polymer and crosslinker concentration affects the performance of an encapsulated LBP toward developing a comprehensive framework for the characterization and optimization of LBP delivery systems. METHODS We encapsulate a model LBP, Lactobacillus casei ATCC 393, in calcium chloride (CaCl2)-crosslinked alginate beads, and evaluate how alginate and CaCl2 concentrations influence LBP formulation performance, including: (i) encapsulation efficiency, (ii) shrinkage upon drying, (iii) survival upon lyophilization, (iv) acid resistance, (v) release, and (vi) metabolite secretion. Approaches from microbiology (e.g., colony forming unit enumeration), materials science (e.g., scanning electron microscopy), and pharmaceutical sciences (e.g., release assays) are employed. RESULTS LBP-encapsulating alginate beads were systematically evaluated as a function of alginate and CaCl2 concentrations. Specifically: (i) encapsulation efficiency of all formulations was >50%, (ii) all alginate beads shrunk (after lyophilization) and recovered (after rehydration) similarly, (iii) at 10% alginate concentration, lower CaCl2 concentration decreased survival upon lyophilization, (iv) 10% alginate improved acid resistance, (v) sustained release was enabled by increasing alginate and CaCl2 concentrations, and (vi) encapsulation did not impair secretion of l-lactate as compared to free LBP. CONCLUSIONS This research demonstrates that polymer content and crosslinking extent modulate the performance of polymer-based LBP delivery systems, motivating research into the optimization of material properties for LBP delivery systems.
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Affiliation(s)
- Kunyu Qiu
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 United States
| | - Yirui Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 United States
| | - Aaron C. Anselmo
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 United States
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Piccioni A, Franza L, Vaccaro V, Saviano A, Zanza C, Candelli M, Covino M, Franceschi F, Ojetti V. Microbiota and Probiotics: The Role of Limosilactobacillus Reuteri in Diverticulitis. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:802. [PMID: 34441008 PMCID: PMC8398895 DOI: 10.3390/medicina57080802] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/29/2021] [Accepted: 08/03/2021] [Indexed: 02/05/2023]
Abstract
The microbiota is the set of commensal microorganisms, residing in the organism, helping proper functioning of organs and systems. The role that the microbiota plays in maintaining the health of vertebrates is widely accepted, particularly in the gastrointestinal system, where it is fundamental for immunity, development, and conversion of nutrients. Dysbiosis is an alteration of the microbiota which refers to a disturbed balance, which can cause a number of pathologies. Probiotics have proven to be effective in modulating the microbiota of the gastrointestinal system and, therefore, in promoting the health of the individual. In particular, Lactobacilli are a group of Gram-positive bacteria, which are able to produce lactic acid through glucose metabolism. They are present in different microenvironments, ranging from the vagina, to the mouth, to different tracts of the small intestine. In the present review, we will discuss the use of Limosilactobacillus in human health in general and more specifically in diverticulitis. In particular we analyze the role of Limosilactobacillus reuteri and its anti-inflammatory action. For this review, articles were identified using the electronic PubMed database through a comprehensive search, conducted by combining key terms such as "diverticulitis", "Limosilactobacillus reuteri", "human health and disease", "probiotics". We selected all the articles published in the last 10 years and screened 1017 papers. Articles referenced in the screened papers were evaluated if considered interesting for our topic. Probiotics have proven to be effective in modulating the microbiota of the gastrointestinal system and, therefore, in promoting the health of the individual. The importance of probiotics in treating diverticular disease and acute diverticulitis can be further understood if taking into consideration some pathophysiological aspects, associated to the microbiota. L. reuteri plays an important role in human health and disease. The effectiveness of L. reuteri in stimulating a correct bowl motility partly explains its effectiveness in treating diverticulitis. The most important action of L. reuteri is probably its immunomodulating activity. Levels of IL-6, IL-8, and Tumor necrosis factor (TNF-alpha) are reduced after supplementation with different strands of Lactobacilli, while T-regulatory cells increase in number and activity. Anyway, new mechanisms of action of probiotics come to light from the many investigations currently taking place in numerous centres around the world and to improve how exactly probiotic administration could make the difference in the management of diverticular disease and acute diverticulitis.
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Affiliation(s)
- Andrea Piccioni
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (M.C.); (M.C.); (F.F.)
| | - Laura Franza
- Emergency Department, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (L.F.); (V.V.); (A.S.); (C.Z.); (V.O.)
| | - Vanessa Vaccaro
- Emergency Department, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (L.F.); (V.V.); (A.S.); (C.Z.); (V.O.)
| | - Angela Saviano
- Emergency Department, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (L.F.); (V.V.); (A.S.); (C.Z.); (V.O.)
| | - Christian Zanza
- Emergency Department, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (L.F.); (V.V.); (A.S.); (C.Z.); (V.O.)
| | - Marcello Candelli
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (M.C.); (M.C.); (F.F.)
| | - Marcello Covino
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (M.C.); (M.C.); (F.F.)
| | - Francesco Franceschi
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (M.C.); (M.C.); (F.F.)
- Emergency Department, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (L.F.); (V.V.); (A.S.); (C.Z.); (V.O.)
| | - Veronica Ojetti
- Emergency Department, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (L.F.); (V.V.); (A.S.); (C.Z.); (V.O.)
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Probiotic-Induced Tolerogenic Dendritic Cells: A Novel Therapy for Inflammatory Bowel Disease? Int J Mol Sci 2021; 22:ijms22158274. [PMID: 34361038 PMCID: PMC8348973 DOI: 10.3390/ijms22158274] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/22/2021] [Accepted: 07/24/2021] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are immune-mediated, chronic relapsing diseases with a rising prevalence worldwide in both adult and pediatric populations. Treatment options for immune-mediated diseases, including IBDs, are traditional steroids, immunomodulators, and biologics, none of which are capable of inducing long-lasting remission in all patients. Dendritic cells (DCs) play a fundamental role in inducing tolerance and regulating T cells and their tolerogenic functions. Hence, modulation of intestinal mucosal immunity by DCs could provide a novel, additional tool for the treatment of IBD. Recent evidence indicates that probiotic bacteria might impact immunomodulation both in vitro and in vivo by regulating DCs’ maturation and producing tolerogenic DCs (tolDCs) which, in turn, might dampen inflammation. In this review, we will discuss this evidence and the mechanisms of action of probiotics and their metabolites in inducing tolDCs in IBDs and some conditions associated with them.
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Abdi M, Lohrasbi V, Asadi A, Esghaei M, Jazi FM, Rohani M, Talebi M. Interesting probiotic traits of mother's milk Lactobacillus isolates; from bacteriocin to inflammatory bowel disease improvement. Microb Pathog 2021; 158:104998. [PMID: 34044041 DOI: 10.1016/j.micpath.2021.104998] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 12/26/2022]
Abstract
AIMS AND BACKGROUND Lactobacillus spp. are an important element in breast milk. This component has a beneficial effect on the composition of the intestinal microflora and the intestinal immune system. The aim of this study was to isolate and identify Lactobacillus strains in breast milk and evaluate some of their probiotic properties, such as presence of bacteriocin genes, adhesion to HT-29 cell line, competition with enteropathogens in cell culture, and effect on serum level of lipids and digestive enzymes, and mice model of inflammatory bowel disease (IBD). MATERIALS AND METHODS A total of 323 lactic acid bacteria (LAB) were isolated from breast milk samples of healthy mothers with the age ranges from 21 to 45 years old. These isolates were subjected to phenotypic and molecular experiments. The frequency of bacteriocin genes was determined by polymerase chain reaction (PCR). Adhesion of Lactobacillus isolates to HT-29 cells was measured based on the number of attached bacterial cells in 20 fields of the light microscopy. Competition test was done by colony count and real-time PCR procedures. Five strongly adhesive Lactobacillus strains were selected and administered orally to the treatment groups. After 8 days, the serum level of digestive enzymes and improvement in induced IBD, and after 14 days, the serum level of lipids (triglycerides, total cholesterol, HDL, and LDL) in treated mice were surveyed compared to the control groups. RESULTS Based on the phenotypic and molecular experiments, L. casei, L. plantarum, L. rhamnosus, and L. acidophilus strains were isolated and identified in the breast milk samples. The highest frequency of bacteriocin genes belonged to Plantaricin B (100%), followed by Plantaricin D (84.7%), Plantaricin G (84.7%), and Plantaricin EF (54.3%). Also, 71.8% of the isolates were strongly adhesive, 21.8% were non-adhesive, and 6.4% were adhesive. Lactobacillus strains had a significant effect on the displacement of enteropathogens. The in vitro cholesterol-removing ability of L. casei (L1), L. casei (L2), L. casei (L3), L. plantarum (L4), and L. rhamnosus (L5) was 3.5, 31.5, 21.3, 18.7, and 27.3%, respectively. The serum level of total cholesterol in the L. plantarum (L4) group as well as LDL in the L. casei (L3) (p = .0108) and L. rhamnosus (L5) (p = .0206) groups decreased significantly compared to the control group. The serum level of lipase increased in all the treatment groups compared to the control group, which was significant in the L. plantarum (L4) group (p = .0390). Disease activity index (DAI) scores were improved significantly in L. casei (L3) group compared to the IBD control group (p < .0001). CONCLUSION It could be concluded that lactobacilli strains isolated from the breast milk samples had good probiotic properties, such as presence of bacteriocin genes, attaching to enterocyte-like HT-29 cells, competing with intestinal pathogens, lowering cholesterol, and improving IBD. Thus, after further studies, they could be considered as probiotic strains.
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Affiliation(s)
- Milad Abdi
- Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Vahid Lohrasbi
- Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Arezoo Asadi
- Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Esghaei
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Faramarz Masjedian Jazi
- Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Rohani
- Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | - Malihe Talebi
- Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Tavakoli P, Vollmer-Conna U, Hadzi-Pavlovic D, Grimm MC. A Review of Inflammatory Bowel Disease: A Model of Microbial, Immune and Neuropsychological Integration. Public Health Rev 2021; 42:1603990. [PMID: 34692176 PMCID: PMC8386758 DOI: 10.3389/phrs.2021.1603990] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 04/01/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: Inflammatory bowel diseases (IBDs) are complex chronic inflammatory disorders of the gastro-intestinal (GI) tract with uncertain etiology. IBDs comprise two idiopathic disorders: Crohn's disease (CD) and ulcerative colitis (UC). The aetiology, severity and progression of such disorders are still poorly understood but thought to be influenced by multiple factors (including genetic, environmental, immunological, physiological, psychological factors and gut microbiome) and their interactions. The overarching aim of this review is to evaluate the extent and nature of the interrelationship between these factors with the disease course. A broader conceptual and longitudinal framework of possible neuro-visceral integration, core microbiome analysis and immune modulation assessment may be useful in accurately documenting and characterizing the nature and temporal continuity of crosstalk between these factors and the role of their interaction (s) in IBD disease activity. Characterization of these interactions holds the promise of identifying novel diagnostic, interventions, and therapeutic strategies. Material and Methods: A search of published literature was conducted by exploring PubMed, EMBASE, MEDLINE, Medline Plus, CDSR library databases. Following search terms relating to key question were set for the search included: "Inflammatory bowel diseases," "gut microbiota," "psychological distress and IBD," "autonomic reactivity and IBD," "immune modulation," "chronic inflammation," "gut inflammation," "enteric nervous system," "gut nervous system," "Crohn's disease," "Ulcerative colitis", "depression and IBD", "anxiety and IBD", "quality of life in IBD patients," "relapse in IBDs," "remission in IBDs," "IBD disease activity," "brain-gut-axis," "microbial signature in IBD," "validated questionnaires in IBD," "IBD activity indices," "IBD aetiology," "IBDs and stress," "epidemiology of IBDs", "autonomic nervous system and gut inflammation", "IBD and environment," "genetics of IBDs," "pathways of immune response in IBDs," "sleep disturbances in IBD," "hypothalamic-pituitary-adrenal axis (HPA)," "sympatho-adrenal axis," "CNS and its control of gut function" "mucosal immune response," "commensal and pathogenic bacteria in the gut," "innate and adaptive immunity." Studies evaluating any possible associations between gut microbiome, psychological state, immune modulation, and autonomic function with IBDs were identified. Commonly cited published literatures with high quality research methodology/results and additional articles from bibliographies of recovered papers were examined and included where relevant. Results: Although there is a substantial literature identifying major contributing factors with IBD, there has been little attempt to integrate some factors over time and assess their interplay and relationship with IBD disease activity. Such contributing factors include genetic and environmental factors, gut microbiota composition and function, physiological factors, psychological state and gut immune response. Interdependences are evident across psychological and biological factors and IBD disease activity. Although from the available evidence, it is implausible that a single explanatory model could elucidate the interplay between such factors and the disease course as well as the sequence of the effect during the pathophysiology of IBD. Conclusion: Longitudinal monitoring of IBD patients and integrating data related to the contributing/risk factors including psychological state, physiological conditions, inflammatory/immune modulations, and microbiome composition/function, could help to explain how major factors associate and interrelate leading to exacerbation of symptoms and disease activity. Identifying the temporal trajectory of biological and psychosocial disturbances may also help to assess their effects and interdependence on individuals' disease status. Moreover, this allows greater insight into understanding the temporal progressions of subclinical events as potential ground for disease severity in IBD. Furthermore, understanding the interaction between these risk factors may help better interventions in controlling the disease, reducing the costs related to disease management, further implications for clinical practice and research approaches in addition to improving patients' mental health and quality of life.
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Affiliation(s)
- P. Tavakoli
- St George and Sutherland Clinical School, Sydney, NSW, Australia
| | - U. Vollmer-Conna
- School of Psychiatry, University of New South Wales, Sydney, Australia
| | - D. Hadzi-Pavlovic
- School of Psychiatry, University of New South Wales, Sydney, Australia
| | - M. C. Grimm
- St George and Sutherland Clinical School, Sydney, NSW, Australia
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29
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Notararigo S, Varela E, Otal A, Cristobo I, Antolín M, Guarner F, Prieto A, López P. Evaluation of an O2-Substituted (1-3)-β-D-Glucan, Produced by Pediococcus parvulus 2.6, in ex vivo Models of Crohn's Disease. Front Microbiol 2021; 12:621280. [PMID: 33613490 PMCID: PMC7893136 DOI: 10.3389/fmicb.2021.621280] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 01/11/2021] [Indexed: 12/19/2022] Open
Abstract
1,3-β-glucans are extracellular polysaccharides synthesized by microorganisms and plants, with therapeutic potential. Among them, the O2-substituted-(1–3)-β-D-glucan, synthesized by some lactic acid bacteria (LAB), has a prebiotic effect on probiotic strains, an immunomodulatory effect on monocyte-derived macrophages, and potentiates the ability of the producer strain to adhere to Caco-2 cells differentiated to enterocytes. In this work, the O2-substituted-(1–3)-β-D-glucan polymers produced by GTF glycoyltransferase in the natural host Pediococcus parvulus 2.6 and in the recombinant strain Lactococcus lactis NZ9000[pNGTF] were tested. Their immunomodulatory activity was investigated in an ex vivo model using human biopsies from patients affected by Crohn’s disease (CD). Both polymers had an anti-inflammatory effect including, a reduction of Interleukine 8 both at the level of its gene expression and its secreted levels. The overall data indicate that the O2-substituted-(1–3)-β-D-glucan have a potential role in ameliorating inflammation via the gut immune system cell modulation.
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Affiliation(s)
- Sara Notararigo
- Department of Microbial: and Plant Biotechnology, Margarita Salas Biological Research Centre (CIB-Margarita Salas-CSIC), Madrid, Spain.,Department of Gastroenterology, Digestive System Research Unit, Institut de Recerca Vall d'Hebron (VHIR), University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.,Foundation Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
| | - Encarnación Varela
- Department of Gastroenterology, Digestive System Research Unit, Institut de Recerca Vall d'Hebron (VHIR), University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Anna Otal
- Department of Gastroenterology, Digestive System Research Unit, Institut de Recerca Vall d'Hebron (VHIR), University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Iván Cristobo
- Department of Microbial: and Plant Biotechnology, Margarita Salas Biological Research Centre (CIB-Margarita Salas-CSIC), Madrid, Spain
| | - María Antolín
- Department of Gastroenterology, Digestive System Research Unit, Institut de Recerca Vall d'Hebron (VHIR), University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Francisco Guarner
- Department of Gastroenterology, Digestive System Research Unit, Institut de Recerca Vall d'Hebron (VHIR), University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Alicia Prieto
- Department of Microbial: and Plant Biotechnology, Margarita Salas Biological Research Centre (CIB-Margarita Salas-CSIC), Madrid, Spain
| | - Paloma López
- Department of Microbial: and Plant Biotechnology, Margarita Salas Biological Research Centre (CIB-Margarita Salas-CSIC), Madrid, Spain
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30
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Lee SY, Lee DY, Kang HJ, Kang JH, Cho MG, Jang HW, Kim BK, Hur SJ. Differences in the gut microbiota between young and elderly persons in Korea. Nutr Res 2021; 87:31-40. [PMID: 33596509 DOI: 10.1016/j.nutres.2020.12.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 11/26/2020] [Accepted: 12/01/2020] [Indexed: 12/13/2022]
Abstract
The gut microbiota differs among countries owing to the prevailing diet composition. For the characterization of the gut microbiota of Koreans at different ages in future studies, e.g., in an in vitro human digestion model, we tried to investigate whether the gut microbiota differs between the young and elderly in Korea. Two hundred fecal samples were collected: 100 from elderly people (over 65 years old) at geriatric nursing hospitals and 100 from young people (university students, 20-25 years old) in Gyeonggi province, Korea. The composition of the gut microbiota in these fecal samples was analyzed by next-generation sequencing methods. There were significant differences in the taxonomic composition of the microbiota (the top 10 most abundant taxa) between the young and elderly people in Korea, especially in terms of relative abundance levels of bacteria in phyla Firmicutes, Proteobacteria, Tenericutes, and Fusobacteria (P < 001). The gut microbiota of young people contained higher relative abundance of Lactobacillus than did the microbiota of elderly people, while the microbiota of elderly people manifested higher relative abundance of Escherichia. Even though the sample size may not be large enough for this study to be representative of the entire population of Korea, the study still provides data that are suggestive of differences in the gut microbiota between young and elderly people in Korea. Furthermore, our findings may be applied to develop an improved age-based in vitro model of digestion of Koreans for future research.
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Affiliation(s)
- Seung Yun Lee
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Da Young Lee
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Hea Jin Kang
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Ji Hyeop Kang
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Min Gi Cho
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Hae Won Jang
- Research Group of Food Processing, Korea Food Research Institute, Jeonbuk 55365, Republic of Korea; Department of Food Science & Biotechnology, sungshin women's university
| | - Bum Keun Kim
- Research Group of Food Processing, Korea Food Research Institute, Jeonbuk 55365, Republic of Korea
| | - Sun Jin Hur
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea.
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31
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Qiu K, Anselmo AC. Batch Culture Formulation of Live Biotherapeutic Products. ADVANCED THERAPEUTICS 2021; 4:2000226. [PMID: 33709021 PMCID: PMC7942761 DOI: 10.1002/adtp.202000226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Indexed: 12/31/2022]
Abstract
Live biotherapeutic products (LBPs) are an emerging therapeutic modality that are clinically investigated for treating pathogenic infections and inflammatory diseases. A major class of LBPs are feces derived microbial consortiums which require numerous process development steps (e.g. separation, purification, blending) to facilitate LBP formulation into oral dosage forms. A subset of these LBPs circumvent the need for continuous fecal processing by batch culture for individual strains of microbes that are rationally defined and combined in the final LBP formulation. Separately, delivery formulations (e.g. polymer encapsulation) are being developed for LBPs to improve storage and intestinal engraftment; however, formulation requires additional manufacturing processes distinct from fecal processing or batch culture. Here, a streamlined approach termed batch culture formulation (BCF) is developed to combine the individual batch culture and formulation processes into a single-step process. Based on a previously described polymeric film formulation that encapsulates LBPs, BCF is shown to reduce the number of required processes to formulate LBP-films without altering LBP phenotype, function, or storage profiles compared to the standard LBP-film formulation approach. Additionally, it is demonstrated that BCF facilitates scaled-fabrication from the milligram to gram scale with predictable loading, highlighting the potential that BCF has for clinical translation.
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Affiliation(s)
- Kunyu Qiu
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Aaron C Anselmo
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
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32
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Zhuang X, Tian Z, Feng R, Li M, Li T, Zhou G, Qiu Y, Chen B, He Y, Chen M, Zeng Z, Zhang S. Fecal Microbiota Alterations Associated With Clinical and Endoscopic Response to Infliximab Therapy in Crohn's Disease. Inflamm Bowel Dis 2020; 26:1636-1647. [PMID: 33026078 DOI: 10.1093/ibd/izaa253] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Gut microbiota dysbiosis is associated with the occurrence and development of Crohn disease (CD). Currently, infliximab (IFX) is used more and more to treat CD; however, gut microbiota alterations during IFX therapy are variable and sometimes even contradictory. We longitudinally identified microbial changes during IFX therapy associated with the clinical and endoscopic response to IFX treatment in CD. METHODS Fecal-associated microbiota was analyzed using 16S sequencing in 49 patients with active CD who were prospectively recruited at baseline, week 6, and week 30, respectively. Moreover, a model trained on the gut microbiota alterations at week 6 was developed to investigate their potential to predict clinical and endoscopic responses to IFX therapy at weeks 14 and 30. RESULTS Characteristics of fecal microbiota composition in patients with CD after IFX treatment displayed an increased diversity and richness, a significant gain in short-chain fatty acid -producing bacteria, and a loss of pathogenic bacteria. Furthermore, certain functional profiles of Kyoto Encyclopedia of Genes and Genomes pathways were predictably altered during the treatment period. Increased proportions of Lachnospiraceae and Blautia were associated with IFX efficacy; the combined increase of these taxa at week 6 showed 83.4% and 84.2% accuracy in predicting clinical response at weeks 14 and 30, respectively, with a predictive value of 89.1% in predicting endoscopic response at week 30. CONCLUSIONS We found that IFX diminished CD-related gut microbial dysbiosis by modifying microbiota composition and function. Specifically, increased Lachnospiraceae and Blautia at week 6 are associated with the clinical and endoscopic response to IFX, providing potentially predictive biomarkers for IFX treatment decision-making.
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Affiliation(s)
- Xiaojun Zhuang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhenyi Tian
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Manying Li
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Tong Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Gaoshi Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Baili Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Shenghong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
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33
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Longhi G, van Sinderen D, Ventura M, Turroni F. Microbiota and Cancer: The Emerging Beneficial Role of Bifidobacteria in Cancer Immunotherapy. Front Microbiol 2020; 11:575072. [PMID: 33013813 PMCID: PMC7507897 DOI: 10.3389/fmicb.2020.575072] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 08/17/2020] [Indexed: 12/15/2022] Open
Abstract
Many intestinal bacteria are believed to be involved in various inflammatory and immune processes that influence tumor etiology because of their metabolic properties and their ability to alter the microbiota homeostasis. Although many functions of the microbiota are still unclear, there is compelling experimental evidence showing that the intestinal microbiota is able to modulate carcinogenesis and the response to anticancer therapies, both in the intestinal tract and other body sites. Among the wide variety of gut-colonizing microorganisms, various species belonging to the Bifidobacterium genus are believed to elicit beneficial effects on human physiology and on the host-immune system. Recent findings, based on preclinical mouse models and on human clinical trials, have demonstrated the impact of gut commensals including bifidobacteria on the efficacy of tumor-targeting immunotherapy. Although the underlying molecular mechanisms remain obscure, bifidobacteria and other microorganisms have become a promising aid to immunotherapeutic procedures that are currently applied to treat cancer. The present review focuses on strategies to recruit the microbiome in order to enhance anticancer responses and develop therapies aimed at fighting the onset and progression of malignancies.
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Affiliation(s)
- Giulia Longhi
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
| | - Douwe van Sinderen
- Alimentary Pharmabotic Centre (APC) Microbiome Institute and School of Microbiology, Bioscience Institute, National University of Ireland, Cork, Ireland
| | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy.,Microbiome Research Hub, University of Parma, Parma, Italy
| | - Francesca Turroni
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy.,Microbiome Research Hub, University of Parma, Parma, Italy
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34
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Wang G, Huang S, Cai S, Yu H, Wang Y, Zeng X, Qiao S. Lactobacillus reuteri Ameliorates Intestinal Inflammation and Modulates Gut Microbiota and Metabolic Disorders in Dextran Sulfate Sodium-Induced Colitis in Mice. Nutrients 2020; 12:nu12082298. [PMID: 32751784 PMCID: PMC7468961 DOI: 10.3390/nu12082298] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 12/11/2022] Open
Abstract
Lactobacillus reuteri, a commensal intestinal bacteria, has various health benefits including the regulation of immunity and intestinal microbiota. We examined whether L. reuteri I5007 could protect mice against colitis in ameliorating inflammation, modulating microbiota, and metabolic composition. In vitro, HT-29 cells were cultured with L. reuteri I5007 or lipopolysaccharide treatment under three different conditions, i.e., pre-, co- (simultaneous), and posttreatment. Pretreatment with L. reuteri I5007 effectively relieves inflammation in HT-29 cells challenged with lipopolysaccharide. In vivo, mice were given L. reuteri I5007 by gavage throughout the study, starting one week prior to dextran sulfate sodium (DSS) treatment for one week followed by two days without DSS. L. reuteri I5007 improved DSS-induced colitis, which was confirmed by reduced weight loss, colon length shortening, and histopathological damage, restored the mucus layer, as well as reduced pro-inflammatory cytokines levels. Analysis of 16S rDNA sequences and metabolome demonstrates that L. reuteri I5007 significantly alters colonic microbiota and metabolic structural and functional composition. Overall, the results demonstrate that L. reuteri I5007 pretreatment could effectively alleviate intestinal inflammation by regulating immune responses and altering the composition of gut microbiota structure and function, as well as improving metabolic disorders in mice with colitis.
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Affiliation(s)
- Gang Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
| | - Shuo Huang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
| | - Shuang Cai
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
| | - Haitao Yu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
| | - Yuming Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
| | - Xiangfang Zeng
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
| | - Shiyan Qiao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (G.W.); (S.H.); (S.C.); (H.Y.); (Y.W.); (X.Z.)
- Beijing Key Laboratory of Biological Feed Additive, China Agricultural University, Beijing 100193, China
- Correspondence: ; Tel.: +86-10-6273-1456
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35
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Microbial Signature in Adipose Tissue of Crohn's Disease Patients. J Clin Med 2020; 9:jcm9082448. [PMID: 32751800 PMCID: PMC7465250 DOI: 10.3390/jcm9082448] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 02/08/2023] Open
Abstract
Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.
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36
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Park SK, Kim HN, Choi CH, Im JP, Cha JM, Eun CS, Kim TO, Kang SB, Bang KB, Kim HG, Jung Y, Yoon H, Han DS, Lee CW, Ahn K, Kim HL, Park DI. Differentially Abundant Bacterial Taxa Associated with Prognostic Variables of Crohn's Disease: Results from the IMPACT Study. J Clin Med 2020; 9:E1748. [PMID: 32516912 PMCID: PMC7357029 DOI: 10.3390/jcm9061748] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/30/2020] [Accepted: 06/02/2020] [Indexed: 12/18/2022] Open
Abstract
Limited studies have examined the intestinal microbiota composition in relation to Crohn's disease (CD) prognosis. We analyzed the differences in microbial communities and relevant metabolic pathways associated with prognostic variables in patients with CD. We applied 16S rRNA gene sequencing to analyze a cohort of 1110 CD and healthy control (HC) fecal samples. We categorized patients with CD into good (CD-G), intermediate (CD-I) and poor (CD-P) prognosis groups, according to the history of using biologics and intestinal resection. Microbiota α-diversity decreased more in CD-P than CD-G and CD-I. Microbiota ß-diversity in CD-P differed from that in CD-G and CD-I. Thirteen genera and 10 species showed differential abundance between CD-G and CD-P groups. Escherichia coli (p = 0.001) and species Producta (p = 0.01) and genera Lactobacillus (p = 0.003) and Coprococcus (p = 0.01) consistently showed differences between CD-G and CD-P groups after adjusting for confounding variables. Functional profiling suggested that the microbial catabolic pathways and pathways related to enterobacterial common antigen and lipopolysaccharide biosynthesis were better represented in the CD-P group than in the CD-G group, and E. coli were the top contributors to these pathways. CD prognosis is associated with altered microbiota composition and decreased diversity, and E. coli might be causally involved in CD progression, and may have adapted to live in inflammatory environments.
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Affiliation(s)
- Soo-kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea;
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea; (H.-N.K.); (C.-W.L.)
- Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul 06193, Korea; (C.H.C.); (J.P.I.); (T.-O.K.); (H.Y.)
| | - Han-Na Kim
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea; (H.-N.K.); (C.-W.L.)
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul 03063, Korea
| | - Chang Hwan Choi
- Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul 06193, Korea; (C.H.C.); (J.P.I.); (T.-O.K.); (H.Y.)
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06973, Korea
| | - Jong Pil Im
- Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul 06193, Korea; (C.H.C.); (J.P.I.); (T.-O.K.); (H.Y.)
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine, Seoul 02447, Korea;
| | - Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri 11923, Korea; (C.S.E.); (D.-S.H.)
| | - Tae-Oh Kim
- Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul 06193, Korea; (C.H.C.); (J.P.I.); (T.-O.K.); (H.Y.)
- Division of Gastroenterology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan 48108, Korea
| | - Sang-Bum Kang
- Division of Gastroenterology, Department of Internal medicine, Daejeon St. Mary’s Hospital, The Catholic University of Korea, Daejeon 34943, Korea;
| | - Ki Bae Bang
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan 31116, Korea;
| | - Hyun Gun Kim
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul Hospital, Seoul 04401, Korea;
| | - Yunho Jung
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan 31151, Korea;
| | - Hyuk Yoon
- Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul 06193, Korea; (C.H.C.); (J.P.I.); (T.-O.K.); (H.Y.)
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea
| | - Dong-Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri 11923, Korea; (C.S.E.); (D.-S.H.)
| | - Chil-Woo Lee
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea; (H.-N.K.); (C.-W.L.)
| | - Kwangsung Ahn
- Functional Genome Institute, PDXen Biosystems Inc., Daejeon 34129, Korea;
| | - Hyung-Lae Kim
- Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul 07804, Korea;
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea;
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea; (H.-N.K.); (C.-W.L.)
- Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul 06193, Korea; (C.H.C.); (J.P.I.); (T.-O.K.); (H.Y.)
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The protective and pathogenic roles of CXCL17 in human health and disease: Potential in respiratory medicine. Cytokine Growth Factor Rev 2020; 53:53-62. [PMID: 32345516 PMCID: PMC7177079 DOI: 10.1016/j.cytogfr.2020.04.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 04/15/2020] [Indexed: 02/07/2023]
Abstract
C-X-C motif chemokine 17 (CXCL17), plays a functional role in maintaining homeostasis at mucosal barriers. CXCL17 expression is associated with both disease progression and protection in various diseases. The multifactorial mechanistic properties of CXCL17 could be exploited as a therapeutic target C-X-C motif chemokine 17 (CXCL-17) is a novel chemokine that plays a functional role maintaining homeostasis at distinct mucosal barriers, including regulation of myeloid-cell recruitment, angiogenesis, and control of microorganisms. Particularly, CXCL17 is produced along the epithelium of the airways both at steady state and under inflammatory conditions. While increased CXCL17 expression is associated with disease progression in pulmonary fibrosis, asthma, and lung/hepatic cancer, it is thought to play a protective role in pancreatic cancer, autoimmune encephalomyelitis and viral infections. Thus, there is emerging evidence pointing to both a harmful and protective role for CXCL17 in human health and disease, with therapeutic potential for translational applications. In this review, we provide an overview of the discovery, characteristics and functions of CXCL17 emphasizing its clinical potential in respiratory disorders.
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Wang H, Zhang S, Yang F, Xin R, Wang S, Cui D, Sun Y. The gut microbiota confers protection in the CNS against neurodegeneration induced by manganism. Biomed Pharmacother 2020; 127:110150. [PMID: 32330797 DOI: 10.1016/j.biopha.2020.110150] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 03/30/2020] [Accepted: 04/04/2020] [Indexed: 12/15/2022] Open
Abstract
Among all types of pollution, heavy metals are considered the greatest threat to human health, and heavy metals are associated with an increased risk of cardiovascular disease, coronary heart disease and neurodegenerative disorders. Manganese (Mn) exposure is well reported to exert neurotoxicity and various neurodegenerative disorders, but the mechanisms are not clear. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. The changes in chemical signaling, metabolism and gut microbiota associated with Mn exposure have provided deeper insight into the neurotoxic mechanism of Mn. We observed that Mn exposure increases host manganic bioaccumulation, and β-amyloid (Aβ), receptor-interacting protein kinase 3 (RIP3) and caspase-3 production in the brain, and causes hippocampal degeneration and necrosis. Mn exposure led to decreased gut bacterial richness, especially for Prevotellaceae, Fusobacteriaceae and Lactobacillaceae. In addition, Mn exposure altered the metabolism of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Meanwhile, we found correlations between the abundance of certain bacterial species and the level of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Fecal microbiome transplantation from normal rats could alleviate the neurotoxicity of Mn exposure by shaping the gut microbiota. Our findings highlight the role of gut dysbiosis-promoted neurotoxicity in Mn exposure and suggest a novel therapeutic strategy of remodeling the gut microbiota.
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Affiliation(s)
- Hui Wang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
| | - Shidong Zhang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Feng Yang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Ruihua Xin
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Shengyi Wang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Dongan Cui
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Yan Sun
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
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Qiu K, Young I, Woodburn BM, Huang Y, Anselmo AC. Polymeric Films for the Encapsulation, Storage, and Tunable Release of Therapeutic Microbes. Adv Healthc Mater 2020; 9:e1901643. [PMID: 32080981 PMCID: PMC7293827 DOI: 10.1002/adhm.201901643] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 01/27/2020] [Indexed: 12/12/2022]
Abstract
Microbe-based therapeutics (MBTs) are an emerging therapeutic modality for treating gastrointestinal infections and inflammatory bowel diseases. Current formulations for oral delivery of MBTs use capsules to achieve safe gastric transit, but oral formulations that control the spatiotemporal concentration of MBTs are yet to be developed, despite well-established connections between all therapeutics and their location, concentration, and distribution at sites of action. The development of a multi-functional polymer-based encapsulation system to formulate MBTs for enhanced storage and delivery through formulation of a model MBT, Lactobacillus casei ATCC393, is reported here. This approach enables the additive inclusion of excipients and polymers to grant specific functions, toward the development of a modular MBT platform. Through addition of established excipients, the formulation provides long-term storage of the encapsulated MBT. By adding higher molecular weight polymers, the release kinetics of the encapsulated MBTs can be modified. The inclusion of a mucoadhesive polymer significantly increases the adhesion force between the formulation and the intestinal tissue. Together, mucoadhesive and sustained release properties can be used to modulate the spatiotemporal concentration of MBTs. The formulation is compatible with standard oral capsules, thus maintaining existing clinical advantages of oral capsules while providing new functions from film encapsulation.
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Affiliation(s)
- Kunyu Qiu
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Isabella Young
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Blaide M. Woodburn
- Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Yirui Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Aaron C. Anselmo
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
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40
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Zheng Y, Zeng X, Chen T, Peng W, Su W. Chemical Profile, Antioxidative, and Gut Microbiota Modulatory Properties of Ganpu Tea: A Derivative of Pu-erh Tea. Nutrients 2020; 12:nu12010224. [PMID: 31952251 PMCID: PMC7019831 DOI: 10.3390/nu12010224] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 01/08/2020] [Accepted: 01/11/2020] [Indexed: 01/06/2023] Open
Abstract
Ganpu tea is an emerging tea drink produced from Pu-erh tea and the pericarp of Citrus reticulate Chachi (GCP). Recently, it has been increasingly favored by consumers due to the potential health effects and special taste. However, information concerning its chemical profile and biological activities is scarce. In this work, a total of 92 constituents were identified in hot-water extracts of Ganpu tea with ultra-high performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Moreover, the antioxidative and gut microbiota modulatory properties of Ganpu tea were investigated in rats after long-term dietary consumption. Ganpu tea and GCP could significantly enhance the activities of superoxide dismutase (SOD) by 13.4% (p < 0.05) and 15.1% (p < 0.01), as well as the activities of glutathione peroxidase (GSH-Px) by 16.3% (p < 0.01) and 20.5% (p < 0.01), respectively. Both showed better antioxidant capacities than Pu-erh tea. Ganpu tea increased the abundance of Bifidobacterium, Lactobacillus, and Lactococcus, suggesting the potential of Ganpu tea in modulating the gut microbiota to benefit human health. The obtained results provide essential information for further investigation of Ganpu tea.
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Affiliation(s)
| | | | | | | | - Weiwei Su
- Correspondence: ; Tel.: +86-020-84112398
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41
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Tanaka A, Kanmura S, Morinaga Y, Kawabata K, Arima S, Sasaki F, Nasu Y, Tanoue S, Hashimoto S, Takeshita M, Takeda S, Ido A. Oral administration of Lactobacillus plantarum 06CC2 prevents experimental colitis in mice via an anti‑inflammatory response. Mol Med Rep 2020; 21:1181-1191. [PMID: 31922249 PMCID: PMC7002978 DOI: 10.3892/mmr.2020.10925] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 09/09/2019] [Indexed: 12/19/2022] Open
Abstract
Dysbiosis of the enteric microbiota causes gastrointestinal diseases, including colitis. The present study investigated the beneficial effect of Lactobacillus plantarum 06CC2 in experimental colitis in mice. An experimental colitis model in C57BL6 mice was induced using dextran sulfate sodium. Mice were orally administered 06CC2 (06CC2 group) or PBS only (control group) by gavage. The disease activity index (DAI), histological grading, and colon tissue and colonic lamina propria mononuclear cells (LPMCs) were examined macroscopically and histopathologically, and the expression levels of inflammation‑associated cytokines (IL‑6, IL‑12, TNF‑α and IL‑10) in these samples were determined. Compared with the control group, the 06CC2 group exhibited a significantly lower DAI (1.5±0.8 vs. 0.2±0.3, respectively; P<0.05) and pathology score (6.3±1.5 vs. 3.8±1.3, respectively; P<0.05). IL‑10 expression in colonic LPMCs was higher in the 06CC2 group than in the control group, although there was no significant difference in IFN‑γ, IL‑6 or IL‑12 expression in colonic LPMCs between the two groups. In addition, 06CC2 stimulated the production of IL‑10 from CD11b‑positive cells and CD11c‑positive cells in the colon. The 06CC2 strain induced IL‑10 production in the colon and attenuated colon inflammation.
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Affiliation(s)
- Akihito Tanaka
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Yuko Morinaga
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Katsuto Kawabata
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Shiho Arima
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Fumisato Sasaki
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Yuichirou Nasu
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Shiroh Tanoue
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Shinichi Hashimoto
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
| | - Masahiko Takeshita
- Research and Development Division, Minami Nihon Rakuno Kyodo Co., Ltd., Miyazaki 885‑0073, Japan
| | - Shiro Takeda
- Department of Animal Science and Biotechnology, School of Veterinary Medicine, Azabu University, Kanagawa 252‑5201, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
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42
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Newman KM, Vaughn BP. Efficacy of intestinal microbiota transplantation in ulcerative colitis: a review of current literature and knowledge. MINERVA GASTROENTERO 2020; 65. [DOI: 10.23736/s1121-421x.19.02610-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Yang C, Merlin D. Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives. Int J Nanomedicine 2019; 14:8875-8889. [PMID: 32009785 PMCID: PMC6859086 DOI: 10.2147/ijn.s210315] [Citation(s) in RCA: 105] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 10/19/2019] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD), which mainly consists of Crohn’s disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)-based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome- dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug’s residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.
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Affiliation(s)
- Chunhua Yang
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA
| | - Didier Merlin
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA.,Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
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44
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Ghosh T, Beniwal A, Semwal A, Navani NK. Mechanistic Insights Into Probiotic Properties of Lactic Acid Bacteria Associated With Ethnic Fermented Dairy Products. Front Microbiol 2019; 10:502. [PMID: 30972037 PMCID: PMC6444180 DOI: 10.3389/fmicb.2019.00502] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 02/27/2019] [Indexed: 12/15/2022] Open
Abstract
Gut microbes and their metabolites maintain the health and homeostasis of the host by communicating with the host via various biochemical and physical factors. Changing lifestyle, chronic intake of foods rich in refined carbohydrates and fats have caused intestinal dysbiosis and other lifestyle-based diseases. Thus, supplementation with probiotics has gained popularity as biotherapies for improving gut health and treating disorders. Research shows that probiotic organisms enhance gastrointestinal health, immunomodulation, generation of essential micronutrients, and prevention of cancer. Ethnically fermented milk and dairy products are hotspots for novel probiotic organisms and bioactive compounds. These ethnic fermented foods have been traditionally prepared by indigenous populations, and have preserved unique microflora for ages. To apply these unique microflora for amelioration of human health, it is important that probiotic properties of the bacterial species are well studied. Majority of the published research and reviews focus on the probiotic organisms and their properties, fermented food products, isolation techniques, and animal studies with their health pathologies. As a consequence, there is a dearth of information about the underlying molecular mechanism behind probiotics associated with ethnically prepared dairy foods. This review is targeted at stimulating research on understanding these mechanisms of bacterial species and beneficial attributes of ethnically fermented dairy products.
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Affiliation(s)
| | | | | | - Naveen Kumar Navani
- Chemical Biology Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
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45
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Saeed M, Yatao X, Tiantian Z, Qian R, Chao S. 16S ribosomal RNA sequencing reveals a modulation of intestinal microbiome and immune response by dietary L-theanine supplementation in broiler chickens. Poult Sci 2019; 98:842-854. [PMID: 30169691 PMCID: PMC7107316 DOI: 10.3382/ps/pey394] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 08/03/2018] [Indexed: 01/01/2023] Open
Abstract
Despite the availability of abundant literature on green tea, studies on the use of L-theanine (an amino acid found only in green tea) as a feed additive in poultry especially broiler are limited. So, this study was conducted to explore the effects of L-theanine on the intestinal microbiome and immune response in a broiler. A total of 400-d-old chicks were randomly divided into four treatment groups (A, B, C, and D) using a complete randomized design. Treatments were as follows: A, control (basal diet); B, basal diet + 100 mg L-theanine/kg diet; C, basal diet + 200 mg L-theanine/kg diet; and D, basal diet + 300 mg L-theanine/kg diet. Mucosal samples from ileum and jejunum of broiler chicken were extracted at 21 and 42 d of age. Extraction of genomic DNA was followed by amplification of V3 and V4 hypervariable regions of 16S ribosomal RNA. After Illumina sequencing, results revealed that treatment with L-theanine significantly increased the population of Lactobacillus in ileum and jejunum as compared to a control group, but the higher population was observed in jejunum at both 21 and 42 d of age. The overall diversity of the jejunum microbiome in the treatment group was significantly lower than that of the ileum and control group (P < 0.05). Results of this study revealed that mRNA expression of TLRs (TLR-2 and TLR-4) and cytokines (TNF-α, IFN-γ, and IL-2) was decreased in response to treatment with L-theanine. Moreover, the negative correlation of abundance of Lactobacillus was observed with expression of IL-2 and IFN-γ in the intestine and these effects were highly significant (P < 0.01). In summary, our finding revealed that dietary supplementation of L-theanine exhibited a positive influence on intestinal bacteria by supporting beneficial microbes like Lactobacillus while decreasing harmful microbes like Clostridium.
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Affiliation(s)
- Muhammad Saeed
- College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, 712100, P.R China
| | - Xu Yatao
- College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, 712100, P.R China
| | - Zhang Tiantian
- College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, 712100, P.R China
| | - Ren Qian
- College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, 712100, P.R China
| | - Sun Chao
- College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, 712100, P.R China
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Oral Administration of Lactobacillus delbrueckii during the Suckling Phase Improves Antioxidant Activities and Immune Responses after the Weaning Event in a Piglet Model. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:6919803. [PMID: 30944695 PMCID: PMC6421809 DOI: 10.1155/2019/6919803] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 12/16/2018] [Indexed: 01/09/2023]
Abstract
Early colonization in the gut by probiotics influences the progressive development and maturity of antioxidant and immune system functionality in the future. This study investigated the impact of orally administrated Lactobacillus delbrueckii (LAB) during the suckling phase on future antioxidant and immune responses of the host, using a piglet model. One hundred neonatal piglets received saline (CON) or LAB at the amounts of 1, 2, 3, and 4 mL at 1, 3, 7, and 14 d of age, respectively. The piglets were weaned at the age of 21 d and fed until the age of 49 d. Serum, liver, and intestinal samples were obtained at 21, 28, and 49 d of age. The results showed that LAB tended to decrease serum 8-hydroxy-2-deoxyguanosine concentration and decreased the concentration of serum and hepatic malondialdehyde, but increased the activity of hepatic glutathione peroxidase on days 21, 28, and 49. The concentrations of secretory immunoglobulin A and some inflammatory cytokines and chemokines were increased (P < 0.05) in the intestinal mucosa of LAB-treated piglets on days 21, 28, and 49 compared to that of CON piglets. Likewise, protein expression of cyclooxygenase 2 and inducible nitric oxide synthase in the intestine of LAB-treated piglets was increased (P < 0.05) during the whole period. These results indicate that administration of LAB to the suckling piglet could improve antioxidant capacity and stimulate intestinal immune response, and these long-lasting effects are also observed up to 4 weeks after weaning. A proper utilization of LAB to neonates would be beneficial to human and animal's future health.
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Simčič S, Berlec A, Stopinšek S, Štrukelj B, Orel R. Engineered and wild-type L. lactis promote anti-inflammatory cytokine signalling in inflammatory bowel disease patient's mucosa. World J Microbiol Biotechnol 2019; 35:45. [PMID: 30810891 DOI: 10.1007/s11274-019-2615-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 02/06/2019] [Indexed: 12/19/2022]
Abstract
Dysbiosis of intestinal microbiota and aberrant inflammatory responses in gastrointestinal mucosa plays important roles in the development of inflammatory bowel disease (IBD). The purpose of this study was to demonstrate the probiotic activity of Lactococcus lactis and the ability of TNF-α-binding by recombinant L. lactis bearing TNF-α-binding affibodies. Various concentrations of recombinant L. lactis were exposed to TNF-α and its binding measured by ELISA. Mucosal biopsies of patients with active IBD were incubated with various L. lactis strains or E. coli DH5α strain and concentrations of TNF-α, IL-23, and IL-10 in the supernatants determined by ELISA. Recombinant L. lactis, at 1 × 109 and 1 × 108 CFU/mL, bound 22.6% and 18.4%, respectively of TNF-α (p < 0.05). When IBD-mucosa was incubated with any L. lactis strain at 1 × 109 CFU/mL, levels of TNF-α and IL-23 were significantly decreased and that of IL-10 increased relative to that for the sterile culture. Opposite trends were observed with E. coli cultures. Recombinant L. lactis at 1 × 108 CFU/mL bound as much as 62.8% (p = 0.026) of TNF-α in IBD-mucosa supernatants compared with the control strain. L. lactis strains are reported, for the first time, to induce an ex vivo anti-inflammatory cytokine profile in IBD inflamed mucosa. L. lactis could therefore constitute a promising alternative approach for treating IBD.
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Affiliation(s)
- Saša Simčič
- Institute of Microbiology and Immunology, University of Ljubljana, Faculty of Medicine, 1000, Ljubljana, Slovenia
| | - Aleš Berlec
- Department of Biotechnology, Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia
| | - Sanja Stopinšek
- Institute of Microbiology and Immunology, University of Ljubljana, Faculty of Medicine, 1000, Ljubljana, Slovenia.
| | - Borut Štrukelj
- Department of Biotechnology, Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.,Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia
| | - Rok Orel
- Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Bohoričeva 20, 1000, Ljubljana, Slovenia
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Liu M, Zhang X, Hao Y, Ding J, Shen J, Xue Z, Qi W, Li Z, Song Y, Zhang T, Wang N. Protective effects of a novel probiotic strain, Lactococcus lactis ML2018, in colitis: in vivo and in vitro evidence. Food Funct 2019; 10:1132-1145. [DOI: 10.1039/c8fo02301h] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Multiple articles have confirmed that an imbalance of the intestinal microbiota is closely related to aberrant immune responses of the intestines and to the pathogenesis of inflammatory bowel diseases (IBDs).
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49
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Fernández-Tomé S, Montalban-Arques A, Díaz-Guerra A, Galvan-Roman JM, Marin AC, Mora-Gutiérrez I, Ortega Moreno L, Santander C, Sánchez B, Chaparro M, Gisbert JP, Bernardo D. Peptides encrypted in the human intestinal microbial-exoproteome as novel biomarkers and immunomodulatory compounds in the gastrointestinal tract. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.11.036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Rojas-Feria M, Romero-García T, Fernández Caballero-Rico JÁ, Pastor Ramírez H, Avilés-Recio M, Castro-Fernandez M, Chueca Porcuna N, Romero-Gόmez M, García F, Grande L, Del Campo JA. Modulation of faecal metagenome in Crohn’s disease: Role of microRNAs as biomarkers. World J Gastroenterol 2018; 24:5223-5233. [PMID: 30581271 PMCID: PMC6295834 DOI: 10.3748/wjg.v24.i46.5223] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 11/13/2018] [Accepted: 11/16/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn’s disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.
AIM To investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.
METHODS Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.
RESULTS Microbial community was characterized using 16S rRNA gene sequencing in 29 samples (n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates (P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4).
CONCLUSION Changes in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.
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Affiliation(s)
- María Rojas-Feria
- Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
| | - Teresa Romero-García
- Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
| | - Jose Ángel Fernández Caballero-Rico
- Complejo Hospitalario Universitario de Granada, Microbiology, Granada E-18016, Spain
- Facultad de ciencias de la salud. Universidad Europea Miguel de Cervantes, Madrid E-28280, Spain
| | - Helena Pastor Ramírez
- Institute of Biomedicine of Seville, Digestive Diseases, Hospital Universitario Virgen del Rocío and CIBERehd, Seville E-41013, Spain
| | - Marta Avilés-Recio
- Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
| | - Manuel Castro-Fernandez
- Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
| | | | - Manuel Romero-Gόmez
- Institute of Biomedicine of Seville, Digestive Diseases, Hospital Universitario Virgen del Rocío and CIBERehd, Seville E-41013, Spain
| | - Federico García
- Complejo Hospitalario Universitario de Granada, Microbiology, Granada E-18016, Spain
| | - Lourdes Grande
- Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
| | - José A Del Campo
- Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
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