|
1
|
Jans M, Vereecke L. A guide to germ-free and gnotobiotic mouse technology to study health and disease. FEBS J 2025; 292:1228-1251. [PMID: 38523409 DOI: 10.1111/febs.17124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/17/2024] [Accepted: 03/11/2024] [Indexed: 03/26/2024]
Abstract
The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research.
Collapse
Affiliation(s)
- Maude Jans
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Biomedical Molecular Biology, Ghent University, Belgium
| | - Lars Vereecke
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Belgium
| |
Collapse
|
|
2
|
Wang J, He M, Yang M, Ai X. Gut microbiota as a key regulator of intestinal mucosal immunity. Life Sci 2024; 345:122612. [PMID: 38588949 DOI: 10.1016/j.lfs.2024.122612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/14/2024] [Accepted: 04/02/2024] [Indexed: 04/10/2024]
Abstract
Gut microbiota is a complex microbial community with the ability of maintaining intestinal health. Intestinal homeostasis largely depends on the mucosal immune system to defense external pathogens and promote tissue repair. In recent years, growing evidence revealed the importance of gut microbiota in shaping intestinal mucosal immunity. Therefore, according to the existing findings, this review first provided an overview of intestinal mucosal immune system before summarizing the regulatory roles of gut microbiota in intestinal innate and adaptive immunity. Specifically, this review delved into the gut microbial interactions with the cells such as intestinal epithelial cells (IECs), macrophages, dendritic cells (DCs), neutrophils, and innate lymphoid cells (ILCs) in innate immunity, and T and B lymphocytes in adaptive immunity. Furthermore, this review discussed the main effects of gut microbiota dysbiosis in intestinal diseases and offered future research prospects. The review highlighted the key regulatory roles of gut microbiota in intestinal mucosal immunity via various host-microbe interactions, providing valuable references for the development of microbial therapy in intestinal diseases.
Collapse
Affiliation(s)
- Jing Wang
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Mei He
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Ming Yang
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China.
| | - Xiaopeng Ai
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, China.
| |
Collapse
|
|
3
|
Engin ED. Microbiota and Lipotoxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:357-372. [PMID: 39287858 DOI: 10.1007/978-3-031-63657-8_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Gut microbiota is an indispensable commensal partner of human superorganism. The wealth of genetic repertoire provided by these microorganisms extends host's substrate processing capability. Energy and nutrient harvesting machinery primarily depends on the proper function of these organisms. However, the dynamic composition of microbiota changes with age, lifestyle, stress factors, infections, medications, and host pathophysiological conditions. Host immune system is primarily responsible for shaping up the microbial community and sustaining the symbiotic state. This involves controlling the delicate balance between agility toward pathobionts and tolerance toward symbionts. When things go wrong with this crosstalk, dysbiosis may arise.Metabolic syndrome is a multisystemic, low-grade chronic inflammatory disease that involves dyslipidemia, glucose intolerance, insulin resistance, and central obesity. Excess caloric intake with high-sugar and high-fat diet promote high energy harvesting and lipogenesis. The secretion of adipokines accompanies lipid spillover from fat cells, which contribute to insulin resistance and the expansion of adipose tissue in ectopic sites. Proinflammatory cytokines from adipose tissue macrophages increase the extent of adipose dysfunction.The inflammatory nature of obesity and metabolic syndrome recall the connection between dysbiosis and immune dysfunction. A remarkable association exits between obesity, inflammatory bowel disease, gluten-sensitive enteropathy, and dysbiosis. These conditions compromise the gut mucosa barrier and allow lipopolysaccharide to enter circulation. Unresolved chronic inflammation caused by one condition may overlap or trigger the other(s). Experimental studies and therapeutic trials of fecal microbiota transplantation promise limited improvement in some of these conditions.Typically, metabolic syndrome is considered as a consequence of overnutrition and the vicious cycle of lipogenesis, lipid accumulation, and chronic low-level inflammation. Because of the complex nature of this disorder, it remains inconclusive whether dysbiosis is a cause or consequence of obesity and metabolic syndrome.
Collapse
Affiliation(s)
- Evren Doruk Engin
- Biotechnology Institute, Ankara University, Gumusdere, Ankara, Turkey.
| |
Collapse
|
|
4
|
Li H, Chen C, Li Y, Li Z, Li C, Luan C. Antioxidant Effects and Probiotic Properties of Latilactobacillus sakei MS103 Isolated from Sweet Pickled Garlic. Foods 2023; 12:4276. [PMID: 38231756 DOI: 10.3390/foods12234276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 11/21/2023] [Accepted: 11/25/2023] [Indexed: 01/19/2024] Open
Abstract
Fermented vegetable-based foods, renowned for their unique flavors and human health benefits, contain probiotic organisms with reported in vitro antioxidative effects. This study investigates the probiotic properties of Latilactobacillus sakei MS103 (L. sakei MS103) and its antioxidant activities using an in vitro oxidative stress model based on the hydrogen peroxide (H2O2)-induced oxidative damage of RAW 264.7 cells. L. sakei MS103 exhibited tolerance to extreme conditions (bile salts, low pH, lysozyme, H2O2), antibiotic sensitivity, and auto-aggregation ability. Moreover, L. sakei MS103 co-aggregated with pathogenic Porphyromonas gingivalis cells, inhibited P. gingivalis-induced biofilm formation, and exhibited robust hydrophobic and electrostatic properties that enabled it to strongly bind to gingival epithelial cells and HT-29 cells for enhanced antioxidant effects. Additionally, L. sakei MS103 exhibited other antioxidant properties, including ion-chelating capability and the ability to effectively scavenge superoxide anion free radicals, hydroxyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid, and 2,2-diphenyl-1-picrylhydrazyl. Furthermore, the addition of live or heat-killed L. sakei MS103 cells to H2O2-exposed RAW 264.7 cells alleviated oxidative stress, as reflected by reduced malondialdehyde levels, increased glutathione levels, and the up-regulated expression of four antioxidant-related genes (gshR2, gshR4, Gpx, and npx). These findings highlight L. sakei MS103 as a potential probiotic capable of inhibiting activities of P. gingivalis pathogenic bacteria and mitigating oxidative stress.
Collapse
Affiliation(s)
- Heng Li
- College of Information Technology, Jilin Agricultural University, Chuangchun 130118, China
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China
| | - Changlin Chen
- College of Information Technology, Jilin Agricultural University, Chuangchun 130118, China
| | - Yuanxin Li
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China
| | - Zhengqiang Li
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China
| | - Chen Li
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Chang Luan
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China
- State Key Laboratory of Black Soils Conservation and Utilization, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China
| |
Collapse
|
|
5
|
Tian S, Chu Q, Ma S, Ma H, Song H. Dietary Fiber and Its Potential Role in Obesity: A Focus on Modulating the Gut Microbiota. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:14853-14869. [PMID: 37815013 DOI: 10.1021/acs.jafc.3c03923] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
Dietary fiber is a carbohydrate polymer with ten or more monomeric units that are resistant to digestion by human digestive enzymes, and it has gained widespread attention due to its significant role in health improvement through regulating gut microbiota. In this review, we summarized the interaction between dietary fiber, gut microbiota, and obesity, and the beneficial effects of dietary fiber on obesity through the modulation of microbiota, such as modifying selective microbial composition, producing starch-degrading enzymes, improving gut barrier function, reducing the inflammatory response, reducing trimethylamine N-oxide, and promoting the production of gut microbial metabolites (e.g., short chain fatty acids, bile acids, ferulic acid, and succinate). In addition, factors affecting the gut microbiota composition and metabolites by dietary fiber (length of the chain, monosaccharide composition, glycosidic bonds) were also concluded. Moreover, strategies for enhancing the biological activity of dietary fiber (fermentation technology, ultrasonic modification, nanotechnology, and microfluidization) were subsequently discussed. This review may provide clues for deeply exploring the structure-activity relationship between dietary fiber and antiobesity properties by targeting specific gut microbiota.
Collapse
Affiliation(s)
- Shuhua Tian
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Qiang Chu
- Tea Research Institute, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, PR China
| | - Shaotong Ma
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Huan Ma
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| | - Haizhao Song
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China
| |
Collapse
|
|
6
|
Marano G, Mazza M, Lisci FM, Ciliberto M, Traversi G, Kotzalidis GD, De Berardis D, Laterza L, Sani G, Gasbarrini A, Gaetani E. The Microbiota-Gut-Brain Axis: Psychoneuroimmunological Insights. Nutrients 2023; 15:1496. [PMID: 36986226 PMCID: PMC10059722 DOI: 10.3390/nu15061496] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/18/2023] [Accepted: 03/19/2023] [Indexed: 03/30/2023] Open
Abstract
There is growing interest in the role that the intestinal microbiota and the related autoimmune processes may have in the genesis and presentation of some psychiatric diseases. An alteration in the communication of the microbiota-gut-brain axis, which constitutes a communicative model between the central nervous system (CNS) and the gastro-enteric tract, has been identified as one of the possible causes of some psychiatric diseases. The purpose of this narrative review is to describe evidence supporting a role of the gut microbiota in psychiatric diseases and the impact of diet on microbiota and mental health. Change in the composition of the gut microbiota could determine an increase in the permeability of the intestinal barrier, leading to a cytokine storm. This could trigger a systemic inflammatory activation and immune response: this series of events could have repercussions on the release of some neurotransmitters, altering the activity of the hypothalamic-pituitary-adrenal axis, and reducing the presence of trophic brain factors. Although gut microbiota and psychiatric disorders seem to be connected, more effort is needed to understand the potential causative mechanisms underlying the interactions between these systems.
Collapse
Affiliation(s)
- Giuseppe Marano
- Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Marianna Mazza
- Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesco Maria Lisci
- Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Michele Ciliberto
- Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gianandrea Traversi
- Unit of Medical Genetics, Department of Laboratory Medicine, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00168 Rome, Italy
| | - Georgios Demetrios Kotzalidis
- Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sant’Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy
| | | | - Lucrezia Laterza
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gabriele Sani
- Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Eleonora Gaetani
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| |
Collapse
|
|
7
|
The Protective Effects of Nutraceutical Components in Methotrexate-Induced Toxicity Models—An Overview. Microorganisms 2022; 10:microorganisms10102053. [PMID: 36296329 PMCID: PMC9608860 DOI: 10.3390/microorganisms10102053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/11/2022] [Accepted: 10/13/2022] [Indexed: 12/04/2022] Open
Abstract
There are multiple concerns associated with methotrexate (MTX), widely recognized for anti-neoplastic and anti-inflammatory effects in life-threatening disease conditions, i.e., acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, psoriasis, and rheumatoid arthritis, due to long-term side effects and associated toxicity, which limits its valuable potential. MTX acts as an inhibitor of dihydrofolate reductase, leading to suppression of purine and pyrimidine synthesis in high metabolic and turnover cells, targeting cancer and dysregulated immune cells. Due to low discrimination between neoplastic cells and naturally high turnover cells, MTX is prone to inhibiting the division of all fast-dividing cells, causing toxicity in multiple organs. Nutraceutical compounds are plant-based or food-derived compounds, used for their preventive and therapeutic role, ascertained in multiple organ dysfunctions, including cardiovascular disease, ischemic stroke, cancer, and neurodegenerative diseases. Gut microbiota and microbiota-derived metabolites take part in multiple physiological processes, their dysregulation being involved in disease pathogenesis. Modulation of gut microbiota by using nutraceutical compounds represents a promising therapeutic direction to restore intestinal dysfunction associated with MTX treatment. In this review, we address the main organ dysfunctions induced by MTX treatment, and modulations of them by using nutraceutical compounds. Moreover, we revealed the protective mechanisms of nutraceuticals in MTX-induced intestinal dysfunctions by modulation of gut microbiota.
Collapse
|
|
8
|
An R, Robbins D, Rey FE, Thibeault SL. Vocal fold mucus layer: Comparison of histological protocols for visualization in mice. Laryngoscope Investig Otolaryngol 2022; 7:444-453. [PMID: 35434350 PMCID: PMC9008169 DOI: 10.1002/lio2.743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 01/06/2022] [Accepted: 01/11/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Ran An
- Department of Surgery, School of Medicine and Public Health University of Wisconsin‐Madison Madison Wisconsin USA
| | - Daniel Robbins
- Department of Surgery, School of Medicine and Public Health University of Wisconsin‐Madison Madison Wisconsin USA
| | - Federico E. Rey
- Department of Bacteriology, College of Agricultural and Life Sciences University of Wisconsin‐Madison Madison Wisconsin USA
| | - Susan L. Thibeault
- Department of Surgery, School of Medicine and Public Health University of Wisconsin‐Madison Madison Wisconsin USA
| |
Collapse
|
|
9
|
Abstract
Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.
Collapse
Affiliation(s)
- Roberto Pacifici
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA
- Emory Microbiome Research Center, Emory University, Atlanta, GA, USA
- Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA
| |
Collapse
|
|
10
|
Huang J, Shan W, Li F, Wang Z, Cheng J, Lu F, Guo E, Beejadhursing R, Xiao R, Liu C, Yang B, Li X, Fu Y, Xi L, Wang S, Ma D, Chen G, Sun C. Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice. Aging (Albany NY) 2021; 13:7589-7607. [PMID: 33658399 PMCID: PMC7993734 DOI: 10.18632/aging.202627] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 11/10/2020] [Indexed: 11/25/2022]
Abstract
Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks’ old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.
Collapse
Affiliation(s)
- Jia Huang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Wanying Shan
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Fuxia Li
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Zizhuo Wang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Jing Cheng
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, People's Republic of China
| | - Funian Lu
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Ensong Guo
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Rajluxmee Beejadhursing
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Rourou Xiao
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Chen Liu
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Bin Yang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Xi Li
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Yu Fu
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Ling Xi
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Shixuan Wang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Ding Ma
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Gang Chen
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Chaoyang Sun
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| |
Collapse
|
|
11
|
Sánchez Macarro M, Ávila-Gandía V, Pérez-Piñero S, Cánovas F, García-Muñoz AM, Abellán-Ruiz MS, Victoria-Montesinos D, Luque-Rubia AJ, Climent E, Genovés S, Ramon D, Chenoll E, López-Román FJ. Antioxidant Effect of a Probiotic Product on a Model of Oxidative Stress Induced by High-Intensity and Duration Physical Exercise. Antioxidants (Basel) 2021; 10:323. [PMID: 33671691 PMCID: PMC7926771 DOI: 10.3390/antiox10020323] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/16/2021] [Accepted: 02/18/2021] [Indexed: 01/02/2023] Open
Abstract
This randomized double-blind and controlled single-center clinical trial was designed to evaluate the effect of a 6-week intake of a probiotic product (1 capsule/day) vs. a placebo on an oxidative stress model of physical exercise (high intensity and duration) in male cyclists (probiotic group, n = 22; placebo, n = 21). This probiotic included three lyophilized strains (Bifidobacterium longum CECT 7347, Lactobacillus casei CECT 9104, and Lactobacillus rhamnosus CECT 8361). Study variables were urinary isoprostane, serum malondialdehyde (MDA), serum oxidized low-density lipoprotein (Ox-LDL), urinary 8-hydroxy-2'-deoxiguanosine (8-OHdG), serum protein carbonyl, serum glutathione peroxidase (GPx), and serum superoxide dismutase (SOD). At 6 weeks, as compared with baseline, significant differences in 8-OHdG (Δ mean difference -10.9 (95% CI -14.5 to -7.3); p < 0.001), MDA (Δ mean difference -207.6 (95% CI -349.1 to -66.1; p < 0.05), and Ox-LDL (Δ mean difference -122.5 (95% CI -240 to -4.5); p < 0.05) were found in the probiotic group only. Serum GPx did not increase in the probiotic group, whereas the mean difference was significant in the placebo group (477.8 (95% CI 112.5 to 843.2); p < 0.05). These findings suggest an antioxidant effect of this probiotic on underlying interacting oxidative stress mechanisms and their modulation in healthy subjects. The study was registered in ClinicalTrials.gov (NCT03798821).
Collapse
Affiliation(s)
- Maravillas Sánchez Macarro
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | - Vicente Ávila-Gandía
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | - Silvia Pérez-Piñero
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | - Fernando Cánovas
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | - Ana María García-Muñoz
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | - María Salud Abellán-Ruiz
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | | | - Antonio J Luque-Rubia
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
| | - Eric Climent
- Research and Development Department, ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, 46980 Valencia, Spain
| | - Salvador Genovés
- Research and Development Department, ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, 46980 Valencia, Spain
| | - Daniel Ramon
- Research and Development Department, ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, 46980 Valencia, Spain
| | - Empar Chenoll
- Research and Development Department, ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, 46980 Valencia, Spain
| | - Francisco Javier López-Román
- Department of Exercise Physiology, San Antonio Catholic University of Murcia (UCAM), 30107 Murcia, Spain
- Primary Care Research Group, Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain
| |
Collapse
|
|
12
|
Abstract
Purpose of the review In this review, we discuss the roles of the gut microbiota, dietary phytochemicals in improving human health. Recent studies have reported that the human gut microbiota can be altered by dietary phytochemicals including phenolics, carotenoids, and dietary fibers. In addition, both pathogenic and nonpathogenic bacteria show regulatory effects with phytochemicals, suggesting potential synergistic effects in the improvement of human gut health and prevention of chronic diseases. Recent findings Numerous studies have been conducted on gut microbial alterations induced by phytochemicals, such as phenolics and carotenoids. Butyrate, a short-chain fatty acid produced via bacterial fermentation in the colon, also shows a significantly beneficial effect in the maintenance of gut microbial homeostasis. However, the molecular mechanisms underlying the effects of diets and the interactions of the gut microorganisms remain poorly understood. The gut microbiome profile changes have been observed in chronic inflammation-induced diseases including colitis, Crohn's disease, immune dysfunction, colon cancer, obesity and diabetes. The anti-inflammatory effects of dietary phytochemicals against these diseases may be partially mediated by regulation of microbial profiles. Latest advances in biomedical technology such as the next-generation sequencing (NGS), and continuous cost reduction associated with these technologies, enabled researchers to perform ever-increasing number of large-scale, high-throughput computational analyses to elucidate the potential mechanism of phytochemical-microbiome interactions. Summary Information obtained from these studies may provide valuable insights to guide future clinical research for the development of therapeutics, botanicals and drug efficacy testing, many of which will be discussed in this review.
Collapse
|
|
13
|
Khandaker GM, Meyer U, Jones PB. From Infection to the Microbiome: An Evolving Role of Microbes in Schizophrenia. Curr Top Behav Neurosci 2019; 44:67-84. [PMID: 30847804 PMCID: PMC6732248 DOI: 10.1007/7854_2018_84] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The study of microorganisms such as bacteria, viruses, archaea, fungi, and protozoa in the context of psychiatric disorders may be surprising to some. This intersection of disciplines, however, has a rich history and is currently revitalized by newfound functions of the microbiome and the gut-brain axis in human diseases. Schizophrenia, in particular, fits this model as a disorder with gene and environmental roots that may be anchored in the immune system. In this context, the combination of a precisely timed pathogen exposure in a person with genetically encoded altered immunity may have especially destructive consequences for the central nervous system (CNS). Furthermore, significant components of immunity, such as the development of the immune response and the concept of immune tolerance, are largely dictated by the commensal residents of the microbiome. When this community of microbes is imbalanced, perhaps as the result of a pathogen invasion, stress, or immune gene deficiency, a pathological cycle of localized inflammation, endothelial barrier compromise, translocation of gut-derived products, and systemic inflammation may ensue. If these pathologies enable access of gut and microbial metabolites and immune molecules to the CNS across the blood-brain barrier (BBB), and studies of the gut-brain axis support this hypothesis, a worsening of cognitive deficits and psychiatric symptoms is predicted to occur in susceptible individuals with schizophrenia. In this chapter, we review the role of microbes in various stages of this model and how these organisms may contribute to documented phenotypes of schizophrenia. An increased understanding of the role of pathogens and the microbiome in psychiatric disorders will better guide the development of microbial and immune-based therapeutics for disease prevention and treatment.
Collapse
Affiliation(s)
- Golam M. Khandaker
- grid.5335.00000000121885934Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - Urs Meyer
- grid.5801.c0000 0001 2156 2780Verhaltensneurobiologie, ETH Zürich, Schwerzenbach, Switzerland
| | - Peter B. Jones
- grid.5335.00000000121885934Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK
| |
Collapse
|
|
14
|
Alam A, Neish A. Role of gut microbiota in intestinal wound healing and barrier function. Tissue Barriers 2018; 6:1539595. [PMID: 30404570 PMCID: PMC6389125 DOI: 10.1080/21688370.2018.1539595] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 09/30/2018] [Accepted: 10/11/2018] [Indexed: 12/19/2022] Open
Abstract
The mammalian intestine harbors a highly complex and abundant ensemble of bacteria that flourish in a nutrient-rich environment while profoundly influencing many aspects of host biology. The intestine coevolved with its resident microbes in a manner where the mucosa developed a barrier function to segregate the resident microbes from the rest of the body, and yet paradoxically, allowing integration of microbial signals for the host benefit. In this review, we provided a comprehensive overview of why the gut microbiota is key to the efficient development and maintenance of the intestinal barrier. We also highlighted how a destabilized equilibrium between gut microbiota and the host may eventuate in a wide range of intestinal diseases characterized by the disrupted intestinal barrier. Finally, the review delineated how microenvironmental changes in the injured mucosa result in an enrichment of a pro-regenerating consortium of bacteria, which augments mucosal wound repair and restoration of barrier functions.
Collapse
Affiliation(s)
- Ashfaqul Alam
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, USA
| | - Andrew Neish
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, USA
| |
Collapse
|
|
15
|
Laing B, Barnett MPG, Marlow G, Nasef NA, Ferguson LR. An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets. Expert Rev Gastroenterol Hepatol 2018; 12:969-983. [PMID: 30052094 DOI: 10.1080/17474124.2018.1505497] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.
Collapse
Affiliation(s)
- Bobbi Laing
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,b School of Nursing, Faculty of Medical and Health Sciences , The University of Auckland , Auckland , New Zealand
| | - Matthew P G Barnett
- c Food Nutrition & Health Team, Food & Bio-Based Products Group , AgResearch Limited , Palmerston North , New Zealand.,d Liggins Institute , The High-Value Nutrition National Science Challenge , Auckland , New Zealand.,e Riddet Institute , Massey University , Palmerston North , New Zealand
| | - Gareth Marlow
- f Institute of Medical Genetics , Cardiff University , Cardiff , Wales , UK
| | - Noha Ahmed Nasef
- e Riddet Institute , Massey University , Palmerston North , New Zealand.,g College of Health, Massey Institute of Food Science and Technology , Palmerston North , New Zealand
| | - Lynnette R Ferguson
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,h Auckland Cancer Research Society, Faculty of Medical and Health Sciences, Grafton Campus , The University of Auckland , Auckland , New Zealand
| |
Collapse
|
|
16
|
Jones RM, Mulle JG, Pacifici R. Osteomicrobiology: The influence of gut microbiota on bone in health and disease. Bone 2018; 115:59-67. [PMID: 28433758 DOI: 10.1016/j.bone.2017.04.009] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 04/18/2017] [Accepted: 04/18/2017] [Indexed: 12/22/2022]
Affiliation(s)
- Rheinallt M Jones
- Department of Pediatrics, Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Jennifer G Mulle
- Department of Human Genetics, Emory University School of Medicine, United States
| | - Roberto Pacifici
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, United States; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, United States.
| |
Collapse
|
|
17
|
Abstract
Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia. At the forefront of this investigative effort is the immune system and its many components, pathways and phenotypes, which are now known to actively engage the brain. Studies in schizophrenia reveal an intricate association of environmentally-driven immune activation in concert with a disrupted genetic template. A consistent conduit through this gene-environmental milieu is the gut-brain axis, which when dysregulated can generate pathological autoimmunity. In this review, we present epidemiological and biochemical evidence in support of an autoimmune component in schizophrenia and depict gut processes and a dysbiotic microbiome as a source and perpetuator of autoimmune dysfunction in the brain. Within this framework, we review the role of infectious agents, inflammation, gut dysbioses and autoantibody propagation on CNS pathologies such as neurotransmitter receptor hypofunction and complement pathway-mediated synaptic pruning. We then review the new pharmacotherapeutic horizon and novel agents directed to impact these pathological conditions. At the core of this discourse is the understanding that schizophrenia is etiologically and pathophysiologically heterogeneous and thus its treatment requires individualized attention with disease state variants diagnosed with objective biomarkers.
Collapse
Affiliation(s)
| | | | - Robert H Yolken
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
18
|
KOLINSKA J, ZAKOSTELECKA M, ZEMANOVA Z, LISA V, GOLIAS J, KOZAKOVA H, DVORAK B. Cellular Differentiation of Non-Transformed Intestinal Epithelial Cells Is Regulated by Lactobacillus rhamnosus and L. casei Strains. Physiol Res 2018; 67:261-273. [DOI: 10.33549/physiolres.933643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The aim of this study was to characterize an in vitro modulating effect of three commensal Lactobacillus strains on cellular differentiation of non-transformed crypt-like rat small intestinal cell line IEC-18. IEC-18 was grown on extracellular matrix, with or without presence of Lactobacillus strains. Gene expression of IEC-18 bacterial detection system – such as Toll-like receptors TLR-2, TLR-4, signal adapter MyD88, cytoplasmic NOD2 receptor, inflammatory cytokines IL-18, IL-1β, chemokine IL-8 and enzyme caspase-1 – was evaluated using real-time PCR. Expression and localization of TLR-2, TLR-4, IL-18 and caspase-1 proteins was demonstrated by Western blotting and immunofluorescent staining. Secretion of IL-18 to apical and basolateral surfaces was assayed by ELISA. Our results suggested that L. casei LOCK0919 accelerated differentiation of IEC-18 by stimulating TLR-2, TLR-4, MyD88, IL-18, caspase-1 mRNAs and proteins. L. casei LOCK0919 increased expression and transfer of villin and β-catenin from cytoplasm to cell membrane. Presence of L. rhamnosus LOCK0900 resulted in detachment of IEC-18 layer from extracellular matrix leading to induction of IL-1β, of TLR-2 and IL-8 mRNAs and stimulation of MyD88, caspase-1 and cytosolic receptor NOD2 mRNAs. L. rhamnosus LOCK0908 was not recognized by TLR-2 or TLR-4 receptors. Lactobacilli-IEC-18 crosstalk enhanced immune and barrier mucosal functions.
Collapse
Affiliation(s)
- J. KOLINSKA
- Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
| | | | | | | | | | | | | |
Collapse
|
|
19
|
Abstract
Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the microbiome. The gastrointestinal tract harbors the greatest numbers of these microorganisms, which regulate human nutrition, metabolism, and immune system function. Moreover, the intestinal microbiota contains pro- and anti-inflammatory products that modulate immune responses and may play a role in maintaining gut barrier function. Therefore, the community composition of the microbiota has profound effects on the immune status of the host and impacts the development and/or progression of inflammatory diseases. Accordingly, numerous studies have shown differences in the microbiota of patients with and without a given inflammatory condition. There is now strong evidence that the gut microbiome regulates bone homeostasis in health and disease, and that prebiotic and probiotics protect against bone loss. Herein, the evidence supporting the role of the microbiota and the effects of prebiotic and probiotics will be reviewed.
Collapse
Affiliation(s)
- Roberto Pacifici
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, Georgia 30322
| |
Collapse
|
|
20
|
Role of intestinal Hsp70 in barrier maintenance: contribution of milk to the induction of Hsp70.2. Pediatr Surg Int 2018; 34:323-330. [PMID: 29196880 DOI: 10.1007/s00383-017-4211-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/05/2017] [Indexed: 10/18/2022]
Abstract
BACKGROUND Necrotizing enterocolitis (NEC) is a gastrointestinal disease of complex etiology resulting in devastating systemic inflammation and often death in premature newborns. We previously demonstrated that formula feeding inhibits ileal expression of heat shock protein-70 (Hsp70), a critical stress protein within the intestine. Barrier function for the premature intestine is critical. We sought to determine whether reduced Hsp70 protein expression increases neonatal intestinal permeability. METHODS Young adult mouse colon cells (YAMC) were utilized to evaluate barrier function as well as intestine from Hsp70-/- pups (KO). Sections of intestine were analyzed by Western blot, immunohistochemistry, and real time PCR. YAMC cells were sub-lethally heated or treated with expressed milk (EM) to induce Hsp70. RESULTS Immunostaining demonstrates co-localized Hsp70 and tight junction protein zona occludens-1 (ZO-1), suggesting physical interaction to protect tight junction function. The permeability of YAMC monolayers increases following oxidant injury and is partially blocked by Hsp70 induction either by prior heat stress or EM. RT-PCR analysis demonstrated that the Hsp70 isoforms, 70.1 and 70.3, predominate in WT pup; however, Hsp70.2 predominates in the KO pups. While Hsp70 is present in WT milk, it is not present in KO EM. Hsp70 associates with ZO-1 to maintain epithelial barrier function. CONCLUSION Both induction of Hsp70 and exposure to EM prevent stress-induced increased permeability. Hsp70.2 is present in both WT and KO neonatal intestine, suggesting a crucial role in epithelial integrity. Induction of the Hsp70.2 isoform appears to be mediated by mother's milk. These results suggest that mother's milk feeding modulates Hsp70.2 expression and could attenuate injury leading to NEC. LEVEL OF EVIDENCE Level III.
Collapse
|
|
21
|
Severance EG, Tveiten D, Lindström LH, Yolken RH, Reichelt KL. The Gut Microbiota and the Emergence of Autoimmunity: Relevance to Major Psychiatric Disorders. Curr Pharm Des 2017; 22:6076-6086. [PMID: 27634185 DOI: 10.2174/1381612822666160914183804] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 08/30/2016] [Accepted: 09/06/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Autoimmune phenotypes are prevalent in major psychiatric disorders. Disequilibria of cellular processes occurring in the gastrointestinal (GI) tract likely contribute to immune dysfunction in psychiatric disorders. As the venue of a complex community of resident microbes, the gut in a homeostatic state equates with a functional digestive system, cellular barrier stability and properly regulated recognition of self and non-self antigens. When gut processes become disrupted as a result of environmental or genetic factors, autoimmunity may ensue. METHODS Here, we review the issues pertinent to autoimmunity and the microbiome in psychiatric disorders and show that many of the reported immune risk factors for the development of these brain disorders are in fact related and consistent with dysfunctions occurring in the gut. We review the few human microbiome studies that have been done in people with psychiatric disorders and supplement this information with mechanistic data gleaned from experimental rodent studies. RESULTS These investigations demonstrate changes in behavior and brain biochemistry directly attributable to alterations in the gut microbiome. We present a model by which autoantigens are produced by extrinsicallyderived food and microbial factors bound to intrinsic components of the gut including receptors present in the enteric nervous system. CONCLUSION This new focus on examining activities outside of the CNS for relevance to the etiology and pathophysiology of psychiatric disorders may require new modalities or a re-evaluation of pharmaceutical targets found in peripheral systems.
Collapse
Affiliation(s)
- Emily G Severance
- Stanley Division of Developmental Neurovirology; Department of Pediatrics; Johns Hopkins University School of Medicine; 600 North Wolfe Street; Blalock 1105; Baltimore, MD 21287, USA
| | | | | | | | | |
Collapse
|
|
22
|
Abstract
Obesity and metabolic syndrome is a multisystemic disorder, that is characterized by excess caloric intake and spillover lipotoxicity caused by ectopic lipid accumulation in non-adipose tissues. Low grade chronic inflammation and insulin resistance are the hallmarks of the disorder, which further aggravate the condition. Gut microbiota constitutes an indispensible part of human superorganism's energy harvesting apparatus. The dynamic composition of microbiota changes with age, life style and host metabolic background. The wealth of genetic repertoire provided by these microorganism enables to extend host's substrate processing and harvesting capability. Some of these compounds including short chain fatty acids and indole act as signalling molecules on mammalian cells and modulate their behaviour. Nonetheless, this symbiotic style of interaction is restrained by immune system. The role of chronic low grade inflammation in metabolic syndrome is well established. Treg cells are the key players that sense and reshape the composition of microbiota. In this regard, any disturbance in Treg functionality may aggravate the inflammation and shift the symbiotic balance towards dysbiosis, which is characterized by autoimmunity and insulin resistance. Thus, immune system is responsible for the modulation of host and microbiota metabolisms and Treg cells act as a bridge in between.
Collapse
|
|
23
|
|
|
24
|
Jones RM, Neish AS. Redox signaling mediated by the gut microbiota. Free Radic Biol Med 2017; 105:41-47. [PMID: 27989756 DOI: 10.1016/j.freeradbiomed.2016.10.495] [Citation(s) in RCA: 126] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 10/17/2016] [Accepted: 10/21/2016] [Indexed: 12/27/2022]
Abstract
The microbiota that inhabits the mammalian intestine can influence a range of physiological functions, including the modulation of immune responses, enhancement epithelial barrier function, and the stimulation of cell proliferation. While the mechanisms by which commensal prokaryotes stimulate immune signaling networks are well-characterized, less is known about the mechanistic control over homeostatic pathways within tissues. Recent reports by our research group have demonstrated that contact between the gut epithelia and some groups of enteric commensal bacteria prompts the rapid generation of reactive oxygen species (ROS) within host cells. Whereas the bacterial-induced production of ROS in phagocytes in response to ligand binding to Formyl Peptide Receptors (FPRs) and ensuing activation of NADPH oxidase 2 (Nox2) is a well-defined mechanism, ROS generated by other cell types such as intestinal epithelia in response to microbial signals via FPRs and the NADPH oxidase 1 (Nox1) is less appreciated. Importantly, enzymatically generated ROS have been shown to function as second messengers in many signal transduction pathways via the transient oxidative activity on sensor proteins bearing oxidant-sensitive thiol groups. Examples of redox sensitive proteins include tyrosine phosphatases that serve as regulators of MAPK pathways, focal adhesion kinase, as well as components involved NF-kB activation. Here, we review the leading edge discoveries gleaned from investigations that focus on microbial-induced generation of ROS and their functional effects on host physiology. These studies identify the functional molecular elements and mechanistic events that mediate the established effects of the normal microbiota on intestinal physiology.
Collapse
Affiliation(s)
- Rheinallt M Jones
- Department of Pediatrics, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michaels St, Room 105-L, Atlanta, GA 30322, United States
| | - Andrew S Neish
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michaels St, Room 105-L, Atlanta, GA 30322, United States.
| |
Collapse
|
|
25
|
Abstract
The large number of intestinal microorganisms, which exceeds the total number of human cells by ten folds, alludes to a significant contribution to human health. This is vivid in enteric and some systemic diseases emanating from disruption of the microbiota. As life style keeps shifting towards disruption of the microbiota in most societies worldwide, interest in the contribution of the microbiota to gut health has grown enormously. Many studies have been conducted to elucidate the exact contribution of the microbiota to human health. The knowledge gained from these studies indicates that the microbiota interacts with the intestinal milieu to maintain gut health. In this review, the crosstalk of microbiota with the intestinal physicochemical barrier pivotal to the gut innate immunity is highlighted. In particular, the review focuses on the role of the microbiota on competitive exclusion of pathogens, intestinal pH, epithelial mechanical barrier integrity, apical actin cytoskeleton, antimicrobial peptides, and the mucus layer. Understanding this microbe-host relationship will provide useful insight into overcoming some diseases related to the disruption of the host microbiota.
Collapse
Affiliation(s)
- J J Malago
- Department of Veterinary Pathology, Faculty of Veterinary Medicine, Sokoine University of Agriculture, P.O. Box 3203, Chuo Kikuu, Morogoro, Tanzania
| |
Collapse
|
|
26
|
Role of intestinal microbiota in the development of multiple sclerosis. Neurologia 2015; 32:175-184. [PMID: 26383059 DOI: 10.1016/j.nrl.2015.07.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 07/07/2015] [Accepted: 07/28/2015] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. DEVELOPMENT We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. CONCLUSIONS Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us.
Collapse
|
|
27
|
Abstract
Genetic and environmental studies implicate immune pathologies in schizophrenia. The body's largest immune organ is the gastrointestinal (GI) tract. Historical associations of GI conditions with mental illnesses predate the introduction of antipsychotics. Current studies of antipsychotic-naïve patients support that gut dysfunction may be inherent to the schizophrenia disease process. Risk factors for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure, cellular barrier defects) are part of biological pathways that intersect those operant in the gut. Central to GI function is a homeostatic microbial community, and early reports show that it is disrupted in schizophrenia. Bioactive and toxic products derived from digestion and microbial dysbiosis activate adaptive and innate immunity. Complement C1q, a brain-active systemic immune component, interacts with gut-related schizophrenia risk factors in clinical and experimental animal models. With accumulating evidence supporting newly discovered gut-brain physiological pathways, treatments to ameliorate brain symptoms of schizophrenia should be supplemented with therapies to correct GI dysfunction.
Collapse
Affiliation(s)
- Emily G Severance
- Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD, 21287-4933, USA,
| | | | | | | |
Collapse
|
|
28
|
Kaur K, Saxena A, Larsen B, Truman S, Biyani N, Fletcher E, Baliga MS, Ponemone V, Hegde S, Chanda A, Fayad R. Mucus mediated protection against acute colitis in adiponectin deficient mice. JOURNAL OF INFLAMMATION-LONDON 2015; 12:35. [PMID: 25949213 PMCID: PMC4422601 DOI: 10.1186/s12950-015-0079-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 04/15/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acute ulcerative colitis is an inflammation-driven condition of the bowel. It hampers the general homeostasis of gut, resulting in decreased mucus production and epithelial cell renewal. Adiponectin (APN), an adipocytokine, is secreted by the adipose tissue and has been debated both as a pro-inflammatory or anti-inflammatory protein depending on the disease condition and microenvironment. The present study delineates the role of APN depletion in mucus modulation in a model of acute colitis. METHODS APNKO and C57BL/6 (WT) male mice were given 2% DSS ad libidum for 5 days in drinking water, followed by normal drinking water for the next 5 days. Hematoxyline-eosin and Alcian Blue staining was used to observe the general colonic morphology and goblet cell quantification respectively. Protein expression levels were quantified by Western blot for MATH1, Hes1, MUC2 and MUC4. ELISA was used to study the levels of TNF-α, IL-6 and IL-1β. RESULTS APNKO mice showed significantly higher goblet to epithelial cell ratios, lower pro-inflammatory cytokines and higher MUC2 levels as compared to the WT mice. The protein expression levels for the mucin MUC2 supported the histopathological findings. An increase in colon tissue-secreted levels of pro-inflammatory with a reduction in anti-inflammatory cytokines in presence of APN support the pro-inflammatory role of APN during acute inflammation. CONCLUSION Absence of APN is protective against DSS-induced acute colonic inflammation by means of reducing colon tissue-secreted pro-inflammatory cytokines, modulating goblet and epithelial cell expressions, and increasing the levels of secretory mucin MUC2.
Collapse
Affiliation(s)
- Kamaljeet Kaur
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA.,Arnold School of Public Health, Applied Physiology Division, University of South Carolina, 921 Assembly St. room 303B, Columbia, SC 29208 USA
| | - Arpit Saxena
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA
| | - Bianca Larsen
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA
| | - Samantha Truman
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA
| | - Nathan Biyani
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA
| | - Emma Fletcher
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA
| | | | | | - Shweta Hegde
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA
| | - Anindya Chanda
- Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208 USA.,Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208 USA
| | - Raja Fayad
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208 USA.,Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208 USA
| |
Collapse
|
|
29
|
Biedermann L, Rogler G. The intestinal microbiota: its role in health and disease. Eur J Pediatr 2015; 174:151-67. [PMID: 25563215 DOI: 10.1007/s00431-014-2476-2] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Revised: 12/08/2014] [Accepted: 12/10/2014] [Indexed: 12/13/2022]
Abstract
UNLABELLED The intestinal microbiota (previously referred to as "intestinal flora") has entered the focus of research interest not only in microbiology but also in medicine. Huge progress has been made with respect to the analysis of composition and functions of the human microbiota. An "imbalance" of the microbiota, frequently also called a "dysbiosis," has been associated with different diseases in recent years. Crohn's disease and ulcerative colitis as two major forms of inflammatory bowel disease, irritable bowel syndrome (IBS) and some infectious intestinal diseases such as Clostridium difficile colitis feature a dysbiosis of the intestinal flora. Whereas this is somehow expected or less surprising, an imbalance of the microbiota or an enrichment of specific bacterial strains in the flora has been associated with an increasing number of other diseases such as diabetes, metabolic syndrome, non-alcoholic fatty liver disease or steatohepatitis and even psychiatric disorders such as depression or multiple sclerosis. It is important to understand the different aspects of potential contributions of the microbiota to pathophysiology of the mentioned diseases. CONCLUSION With the present manuscript, we aim to summarize the current knowledge and provide an overview of the different concepts on how bacteria contribute to health and disease in animal models and-more importantly-humans. In addition, it has to be borne in mind that we are only at the very beginning to understand the complex mechanisms of host-microbial interactions.
Collapse
Affiliation(s)
- Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, 8091, Zürich, Switzerland,
| | | |
Collapse
|
|
30
|
Yoon MY, Yoon MY, Lee K, Yoon SS. Protective role of gut commensal microbes against intestinal infections. J Microbiol 2014; 52:983-9. [PMID: 25467115 DOI: 10.1007/s12275-014-4655-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 11/19/2014] [Accepted: 11/19/2014] [Indexed: 01/06/2023]
Abstract
The human gastrointestinal tract is colonized by multitudes of microorganisms that exert beneficial effects on human health. Mounting evidence suggests that intestinal microbiota contributes to host resistance against enteropathogenic bacterial infection. However, molecular details that account for such an important role has just begun to be understood. The commensal microbes in the intestine regulate gut homeostasis through activating the development of host innate immunity and producing molecules with antimicrobial activities that directly inhibit propagation of pathogenic bacteria. Understanding the protective roles of gut microbiota will provide a better insight into the molecular basis that underlies complicated interaction among host-pathogen-symbiont. In this review, we highlighted recent findings that help us broaden our knowledge of the intestinal ecosystem and thereby come up with a better strategy for combating enteropathogenic infection.
Collapse
Affiliation(s)
- Mi Young Yoon
- Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea
| | - My Young Yoon
- Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea
| | | | | |
Collapse
|
|
31
|
Ramonaite R, Skieceviciene J, Juzenas S, Salteniene V, Kupcinskas J, Matusevicius P, Borutaite V, Kupcinskas L. Protective action of NADPH oxidase inhibitors and role of NADPH oxidase in pathogenesis of colon inflammation in mice. World J Gastroenterol 2014; 20:12533-12541. [PMID: 25253955 PMCID: PMC4168088 DOI: 10.3748/wjg.v20.i35.12533] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 02/11/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in colon epithelial cells in the pathogenesis of acute and chronic colon inflammation in a mouse model of dextran sulphate sodium (DSS)-induced colitis.
METHODS: Balb/c mice were divided into three groups: 8 mice with acute DSS-induced colitis (3.5% DSS solution; 7 d), 8 mice with chronic DSS-induced colitis (3.5% DSS solution for 5 d + water for 6 d; 4 cycles; total: 44 d) and 12 mice without DSS supplementation as a control group. Primary colonic epithelial cells were isolated using chelation method. The cells were cultivated in the presence of mediators (lipopolysaccharide (LPS), apocynin or diphenyleneiodonium). Viability of cells was assessed by fluorescent microscopy. Production of reactive oxygen species (ROS) by the cells was measured fluorometrically using Amplex Red. Production of tumour necrosis factor-alpha (TNF-α) by the colonic epithelial cells was analysed by ELISA. Nox1 gene expression was assessed by real-time PCR.
RESULTS: Our study showed that TNF-α level was increased in unstimulated primary colonic cells both in the acute and chronic colitis groups, whereas decreased viability, increased ROS production, and expression of Nox1 was characteristic only for chronic DSS colitis mice when compared to the controls. The stimulation by LPS increased ROS generation via NADPH oxidase and decreased cell viability in mice with acute colitis. Treatment with NADPH oxidase inhibitors increased cell viability and decreased the levels of ROS and TNF-α in the LPS-treated cells isolated from mice of both acute and chronic colitis groups.
CONCLUSION: Our study revealed the importance of NADPH oxidase in the pathogenesis of both acute and chronic inflammation of the colon.
Collapse
|
|
32
|
Establishment of a Primary Culture Method for Mouse Intestinal Epithelial Cells by Organ Culture of Fetal Small Intestine. Biosci Biotechnol Biochem 2014; 73:1849-55. [DOI: 10.1271/bbb.90246] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
|
|
33
|
McAdam TG, Burnes BS. A pilot study of the effects of environmental and physiological stress on the conjunctival bacteria of college student contact wearers. ACTA ACUST UNITED AC 2014. [DOI: 10.1893/0005-3155-85.2.86] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
|
|
34
|
Barzegari A, Saeedi N, Saei AA. Shrinkage of the human core microbiome and a proposal for launching microbiome biobanks. Future Microbiol 2014; 9:639-56. [DOI: 10.2217/fmb.14.22] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
ABSTRACT: The Human Microbiome Project (HMP) revealed the significance of the gut microbiome in promoting health. Disruptions in microbiome composition are associated with the pathogenesis of numerous diseases. The indigenous microflora has co-evolved with humans for millions of years and humans have preserved the inherited microbiomes through consumption of fermented foods and interactions with environmental microbes. Through modernization, traditional foods were abandoned, native food starters were substituted with industrial products, vaccines and antibiotics were used, extreme hygiene measures were taken, the rate of cesarean section increased, and breast feeding changed into formula. These factors have reduced human exposure to microbial symbionts and led to shrinkage of the core microbiome. Reduction in microbiome biodiversity can compromise the human immune system and predispose individuals to several modern diseases. This article suggests launching microbiome biobanks for archiving native microbiomes, supervising antibiotic use, probiotic design and native starter production, as well as advertising a revisit to native lifestyles.
Collapse
Affiliation(s)
- Abolfazl Barzegari
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- The School of Advanced Biomedical Sciences (SABS), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nazli Saeedi
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Ata Saei
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
35
|
Abstract
The microbiota that populates the intestinal tract affects many physiological processes, such as cell proliferation, epithelial barrier function, and immune responses. However, the molecular mechanisms by which the microbiota influences these events remain unknown. It was recently reported by our research group that specific taxa of intestinal bacteria induce the rapid and transient enzymatic production of reactive oxygen species (ROS) within enterocytes. Whereas NADPH oxidase 2 (Nox2) catalyzed ROS generation in response to microbial perception by bone marrow-derived phagocytes is well-studied, the function of ROS generated by Nox1 in enterocytes in response to microbial signals is not fully understood. It is established that ROS can act as signaling molecules in diverse transduction pathways by the rapid and transient oxidation of oxidant-sensitive thiol groups harbored within sensor regulatory proteins. Because commensal-bacterial-stimulated ROS generation in enterocytes has been shown to induce a wide range of physiological processes, in our recent manuscript, we proposed a paradigm wherein the influence of the microbiota on intestinal physiology is mediated in part by redox-dependant signaling.
Collapse
|
|
36
|
Abstract
The microbiota that occupies the mammalian intestine can modulate a range of physiological functions, including control over immune responses, epithelial barrier function, and cellular proliferation. While commensal prokaryotic organisms are well known to stimulate inflammatory signaling networks, less is known about control over homeostatic pathways. Recent work has shown that gut epithelia contacted by enteric commensal bacteria rapidly generate reactive oxygen species (ROS). While the induced production of ROS in professional phagocytes via stimulation of formyl peptide receptors (FPRs) and activation of NADPH oxidase 2 (Nox2) is a well-studied process, ROS are also similarly elicited in other cell types, including intestinal epithelia, in response to microbial signals via FPRs and the epithelial NADPH oxidase 1 (Nox1). ROS generated by Nox enzymes have been shown to function as critical second messengers in multiple signal transduction pathways via the rapid and transient oxidative inactivation of a distinct class of sensor proteins bearing oxidant-sensitive thiol groups. These redox-sensitive proteins include tyrosine phosphatases that serve as regulators of MAP kinase pathways, focal adhesion kinase, as well as components involved in NF-κB activation. As microbe-elicited ROS has been shown to stimulate cellular proliferation and motility, and to modulate innate immune signaling, we hypothesize that many of the established effects of the normal microbiota on intestinal physiology may be at least partially mediated by this ROS-dependent mechanism.
Collapse
Affiliation(s)
- Andrew S Neish
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA , USA
| |
Collapse
|
|
37
|
Herfel TM, Jacobi SK, Lin X, Jouni ZE, Chichlowski M, Stahl CH, Odle J. Dietary supplementation of Bifidobacterium longum strain AH1206 increases its cecal abundance and elevates intestinal interleukin-10 expression in the neonatal piglet. Food Chem Toxicol 2013; 60:116-22. [PMID: 23872134 DOI: 10.1016/j.fct.2013.07.020] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2013] [Revised: 06/25/2013] [Accepted: 07/09/2013] [Indexed: 11/15/2022]
Abstract
Intestinal microbiota of infants differ in response to gestational age, delivery mode and feeding regimen. Dietary supplementation of probiotic bacteria is one method of promoting healthy populations. We examined the impact of a novel probiotic strain of Bifidobacterium longum (AH1206) on the health, growth and development of neonatal pigs as a model for infants. Day-old pigs were fed milk-based formula containing AH1206 at 0, 10⁹, or 10¹¹ CFU/d for 18 d (n=10/treatment). Differences were not detected in growth, organ weights or body temperatures (P>0.1); however pigs fed the high dose showed a small (2%) reduction in feed intake. Bacterial translocation was not affected as indicated by total anaerobic and aerobic counts (CFU) in samples of spleen, liver and mesenteric lymph nodes (P>0.1). Feeding AH1206 had no effects on fecal consistency, but increased the density of B. longum in the cecum. Ileal TNF expression tended to increase (P=0.08) while IL-10 expression increased linearly (P=0.01) with supplementation. Based upon findings in the suckling piglet model, we suggest that dietary supplementation with B. longum (AH1206) may be safe for human infants based on a lack of growth, development or deleterious immune-related effects observed in piglets.
Collapse
Affiliation(s)
- Tina M Herfel
- Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC 27695-7621, United States.
| | | | | | | | | | | | | |
Collapse
|
|
38
|
Günther C, Neumann H, Neurath MF, Becker C. Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut 2013; 62:1062-71. [PMID: 22689519 DOI: 10.1136/gutjnl-2011-301364] [Citation(s) in RCA: 338] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Intestinal epithelial cells (IEC) are organised as a single cell layer which covers the intestine. Their primary task is to absorb nutrients present in the intestinal lumen. However, IEC also play an important role in the immune defence of our body by building a barrier that separates the bowel wall from potentially hazardous bacteria present in the gut lumen. The life cycle of IEC is determined by the time span in which cells migrate from their place of origin at the crypt base to the villus tip, from where they are shed into the lumen. Cell death in the intestinal epithelium has to be tightly regulated and irregularities might cause pathologies. Excessive cell death has been associated with chronic inflammation as seen in patients with Crohn's disease and ulcerative colitis. While until recently apoptosis was discussed as being essential for epithelial turnover and tissue homeostasis in the intestinal epithelium, recent data using gene deficient mice have challenged this concept. Moreover, an apoptosis-independent mode of programmed cell death, termed necroptosis, has been identified and described in the intestinal epithelium. The following article reviews previous studies on cell death regulation in IEC and a potential role of necroptosis for gut homeostasis.
Collapse
Affiliation(s)
- Claudia Günther
- Department of Medicine, University of Erlangen-Nuremberg, Hartmannstrasse 14, 91 054 Erlangen, Germany
| | | | | | | |
Collapse
|
|
39
|
Chen K, Liu M, Liu Y, Yoshimura T, Shen W, Le Y, Durum S, Gong W, Wang C, Gao JL, Murphy PM, Wang JM. Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis. J Clin Invest 2013; 123:1694-704. [PMID: 23454745 PMCID: PMC3613917 DOI: 10.1172/jci65569] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Accepted: 01/11/2013] [Indexed: 01/24/2023] Open
Abstract
Commensal bacteria and their products provide beneficial effects to the mammalian gut by stimulating epithelial cell turnover and enhancing wound healing, without activating overt inflammation. We hypothesized that N-formylpeptide receptors, which bind bacterial N-formylpeptides and are expressed by intestinal epithelial cells, may contribute to these processes. Here we report that formylpeptide receptor-2 (FPR2), which we show is expressed on the apical and lateral membranes of colonic crypt epithelial cells, mediates N-formylpeptide-dependent epithelial cell proliferation and renewal. Colonic epithelial cells in FPR2-deficient mice displayed defects in commensal bacterium-dependent homeostasis as shown by the absence of responses to N-formylpeptide stimulation, shortened colonic crypts, reduced acute inflammatory responses to dextran sulfate sodium (DSS) challenge, delayed mucosal restoration after injury, and increased azoxymethane-induced tumorigenesis. These results indicate that FPR2 is critical in mediating homeostasis, inflammation, and epithelial repair processes in the colon.
Collapse
Affiliation(s)
- Keqiang Chen
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Mingyong Liu
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Ying Liu
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Teizo Yoshimura
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Wei Shen
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Yingying Le
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Scott Durum
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Wanghua Gong
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Chunyan Wang
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Ji-Liang Gao
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Philip M. Murphy
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| | - Ji Ming Wang
- Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
SAIC-Frederick, Frederick, Maryland, USA.
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
| |
Collapse
|
|
40
|
Adhesive properties of predominant bacteria in raw cow’s milk to bovine mammary gland epithelial cells. Folia Microbiol (Praha) 2013; 58:515-22. [DOI: 10.1007/s12223-013-0240-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Accepted: 03/12/2013] [Indexed: 12/31/2022]
|
|
41
|
Xu X, Xu P, Ma C, Tang J, Zhang X. Gut microbiota, host health, and polysaccharides. Biotechnol Adv 2012; 31:318-37. [PMID: 23280014 DOI: 10.1016/j.biotechadv.2012.12.009] [Citation(s) in RCA: 182] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2012] [Revised: 12/20/2012] [Accepted: 12/21/2012] [Indexed: 02/07/2023]
Abstract
The intestinal microbiota is a complicated ecosystem that influences many aspects of host physiology (i.e. diet, disease development, drug metabolism, and regulation of the immune system). It also exhibits spatial patterning and temporal dynamics. In this review, the effects of internal and external (environmental) factors on intestinal microbiota are discussed. We describe the roles of the gut microbiota in maintaining intestinal and immune system homeostasis and the relationship between gut microbiota and diseases. In particular, the contributions of polysaccharides, as the most abundant diet components in intestinal microbiota and host health are presented. Finally, perspectives for research avenues relating to gut microbiota are also discussed.
Collapse
Affiliation(s)
- Xiaofei Xu
- College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, China
| | | | | | | | | |
Collapse
|
|
42
|
Jones RM, Mercante JW, Neish AS. Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications. Curr Med Chem 2012; 19:1519-29. [PMID: 22360484 DOI: 10.2174/092986712799828283] [Citation(s) in RCA: 174] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2011] [Revised: 12/22/2011] [Accepted: 12/26/2011] [Indexed: 12/18/2022]
Abstract
The resident prokaryotic microbiota of the mammalian intestine influences diverse homeostatic functions, including regulation of cellular growth, maintenance of barrier function, and modulation of immune responses. However, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. Recent data has demonstrated that gut epithelia contacted by enteric commensal bacteria rapidly generate reactive oxygen species (ROS). While the induced generation of ROS via stimulation of formyl peptide receptors is a cardinal feature of the cellular response of phagocytes to pathogenic or commensal bacteria, evidence is accumulating that ROS are also similarly elicited in other cell types, including intestinal epithelia, in response to microbial signals. Additionally, ROS have been shown to serve as critical second messengers in multiple signal transduction pathways stimulated by proinflammatory cytokines and growth factors. This physiologically-generated ROS is known to participate in cellular signaling via the rapid and transient oxidative inactivation of a defined class of sensor proteins bearing oxidant-sensitive thiol groups. These proteins include tyrosine phosphatases that serve as regulators of MAP kinase pathways, cytoskeletal dynamics, as well as components involved in control of ubiquitination-mediated NF-κB activation. Consistently, microbial-elicited ROS has been shown to mediate increased cellular proliferation and motility and to modulate innate immune signaling. These results demonstrate how enteric microbiota influence regulatory networks of the mammalian intestinal epithelia. We hypothesize that many of the known effects of the normal microbiota on intestinal physiology, and potential beneficial effects of candidate probiotic bacteria, may be at least partially mediated by this ROS-dependent mechanism.
Collapse
Affiliation(s)
- R M Jones
- Emory University School of Medicine, Atlanta, GA 30322, USA
| | | | | |
Collapse
|
|
43
|
Thomson ABR, Chopra A, Clandinin MT, Freeman H. Recent advances in small bowel diseases: Part I. World J Gastroenterol 2012; 18:3336-52. [PMID: 22807604 PMCID: PMC3396187 DOI: 10.3748/wjg.v18.i26.3336] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Revised: 04/05/2012] [Accepted: 04/13/2012] [Indexed: 02/06/2023] Open
Abstract
As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician.
Collapse
|
|
44
|
Sahu U, Kar S. Outsider to insider: resetting the natural host niche of commensal E. coli K-12. Bioeng Bugs 2012; 3:133-7. [PMID: 22539026 DOI: 10.4161/bbug.19686] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The status of E. coli K-12 as an exclusively non-invasive, non-pathogenic bacterium has almost been incontrovertible. Our recent finding that a mutation in one of its main architectural protein, HU, converts E. coli K-12 to an actively invasive form suggests that gaining host cell entry might be an expedient survival tactic for traditional commensals during certain altered host conditions. The mutant E. coli (SK3842) exhibits properties usually associated with pathogenic bacteria: host cell invasion, phagosomal disruption and intracellular replication. However, unlike the situation with some pathogens, internalized SK3842 imparts anti-apoptotic and cyto-protective effects rather than lethality on the host cell, both in vitro and in vivo. Here, we show that SK3842 also provides colonization resistance against other invasive pathogens--a trait not shared by the parental commensal strain. Thus, the altered lifestyle of SK3842 encompasses characteristics both from traditional pathogens as well as beneficial probiotic strains.
Collapse
Affiliation(s)
- Upasana Sahu
- Institute of Molecular Medicine, New Delhi, India
| | | |
Collapse
|
|
45
|
Lactobacillus acidophilus induces cytokine and chemokine production via NF-κB and p38 mitogen-activated protein kinase signaling pathways in intestinal epithelial cells. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2012; 19:603-8. [PMID: 22357649 DOI: 10.1128/cvi.05617-11] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Intestinal epithelial cells can respond to certain bacteria by producing an array of cytokines and chemokines which are associated with host immune responses. Lactobacillus acidophilus NCFM is a characterized probiotic, originally isolated from human feces. This study aimed to test the ability of L. acidophilus NCFM to stimulate cytokine and chemokine production in intestinal epithelial cells and to elucidate the mechanisms involved in their upregulation. In experiments using intestinal epithelial cell lines and mouse models, we observed that L. acidophilus NCFM could rapidly but transiently upregulate a number of effector genes encoding cytokines and chemokines such as interleukin 1α (IL-1α), IL-1β, CCL2, and CCL20 and that cytokines showed lower expression levels with L. acidophilus NCFM treatment than chemokines. Moreover, L. acidophilus NCFM could activate a pathogen-associated molecular pattern receptor, Toll-like receptor 2 (TLR2), in intestinal epithelial cell lines. The phosphorylation of NF-κB p65 and p38 mitogen-activated protein kinase (MAPK) in intestinal epithelial cell lines was also enhanced by L. acidophilus NCFM. Furthermore, inhibitors of NF-κB (pyrrolidine dithiocarbamate [PDTC]) and p38 MAPK (SB203580) significantly reduced cytokine and chemokine production in the intestinal epithelial cell lines stimulated by L. acidophilus NCFM, suggesting that both NF-κB and p38 MAPK signaling pathways were important for the production of cytokines and chemokines induced by L. acidophilus NCFM.
Collapse
|
|
46
|
Herfel TM, Jacobi SK, Lin X, Fellner V, Walker DC, Jouni ZE, Odle J. Polydextrose enrichment of infant formula demonstrates prebiotic characteristics by altering intestinal microbiota, organic acid concentrations, and cytokine expression in suckling piglets. J Nutr 2011; 141:2139-45. [PMID: 22013198 DOI: 10.3945/jn.111.143727] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Oligosaccharides, the 3rd-most abundant component in human milk, are virtually absent from infant formulas and from the cow milk on which most are based. In breast-fed infants, human milk oligosaccharides (HMO) act as both receptor analogs, interfering with pathogen adhesion, and as prebiotics, stimulating the growth of certain commensal bacteria (e.g. bifidobacteria) and supporting the innate immunity. To further align the functional properties of infant formula with those of human milk, polydextrose (PDX) is proposed as a substitute for HMO. To determine the prebiotic functionality of PDX, 1-d-old pigs were fed a cow milk-based formula supplemented with increasing concentrations of PDX (0, 1.7, 4.3, 8.5, or 17 g/L) for 18 d (n = 13). Additional reference groups included pigs sampled at d 0 and sow-reared pigs sampled at d 18 (n = 12). Ileal Lactobacilli CFU, but not Bifidobacteria, increased linearly with increasing PDX (P = 0.02). The propionic acid concentration in digesta linearly increased with the PDX level (P = 0.045) and lactic acid increased linearly by 5-fold with increasing PDX (P = 0.001). Accordingly, digesta pH decreased linearly (P < 0.05) as PDX increased, with a maximal reduction approaching 0.5 pH units in pigs fed 17 g/L. Expression of TNFα, IL-1β, and IL-8 showed a negative quadratic pattern in response to PDX supplementation, declining at intermediate concentrations and rebounding at higher concentrations of PDX. In summary, PDX enrichment of infant formula resulted in a prebiotic effect by increasing ileal lactobacilli and propionic and lactic acid concentrations and decreasing pH with associated alterations in ileal cytokine expression.
Collapse
Affiliation(s)
- Tina M Herfel
- Laboratory of Developmental Nutrition, Department of Animal Sciences, North Carolina State University, Raleigh, NC, USA
| | | | | | | | | | | | | |
Collapse
|
|
47
|
Liedel JL, Guo Y, Yu Y, Shiou SR, Chen S, Petrof EO, Hu S, Musch MW, Claud EC. Mother's milk-induced Hsp70 expression preserves intestinal epithelial barrier function in an immature rat pup model. Pediatr Res 2011; 69:395-400. [PMID: 21263375 PMCID: PMC3088164 DOI: 10.1203/pdr.0b013e3182114ec9] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Preterm infants face many challenges in transitioning from the in utero to extrauterine environment while still immature. Failure of the preterm gut to successfully mature to accommodate bacteria and food substrate leads to significant morbidity such as neonatal necrotizing enterocolitis. The intestinal epithelial barrier plays a critical role in gut protection. Heat shock protein 70 (Hsp70) is an inducible cytoprotective molecule shown to protect the intestinal epithelium in adult models. To investigate the hypothesis that Hsp70 may be important for early protection of the immature intestine, Hsp70 expression was evaluated in intestine of immature rat pups. Data demonstrate that Hsp70 is induced by exposure to mother's milk. Hsp70 is found in mother's milk, and increased Hsp70 transcription is induced by mother's milk. This Hsp70 colocalizes with the tight junction protein ZO-1. Mother's milk-induced Hsp70 may contribute to maintenance of barrier function in the face of oxidant stress. Further understanding of the means by which mother's milk increases Hsp70 in the ileum will allow potential means of strengthening the intestinal barrier in at-risk preterm infants.
Collapse
Affiliation(s)
- Jennifer L Liedel
- Department of Pediatrics, The University of Chicago, Chicago, Illinois 60637, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol 2011; 31 Suppl 1:S29-34. [PMID: 21448201 DOI: 10.1038/jp.2010.172] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The intestinal microbiota normally exists in a commensal and/or symbiotic relationship with the host. In the past few years, emerging technologies derived largely from the Human Genome Project have been applied to evaluating the intestinal microbiota and new discoveries using these techniques have prompted new initiatives such as the Human Microbiome Roadmap designed to evaluate the role of the intestinal microbiome in health and disease. In this review, we wish to focus on some new developments in this area and discuss some of the effects of medical manipulations such as antibiotics, probiotics, prebiotics and C-section versus vaginal delivery on the intestinal microbiota.
Collapse
Affiliation(s)
- R Murgas Torrazza
- Division of Neonatology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA
| | | |
Collapse
|
|
49
|
Forsythe P, Bienenstock J. Immunomodulation by commensal and probiotic bacteria. Immunol Invest 2010; 39:429-48. [PMID: 20450286 DOI: 10.3109/08820131003667978] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Over the past decade there has been an increasing awareness of the role played by commensal bacteria in modulating mucosal immune responses and as a consequence there is now great interest in the therapeutic potential of probiotics and other bacteria based strategies for a range of immune disorders. Here we review current understanding of the mechanisms underlying the immunomodulatory actions of commensal and probiotic bacteria and probiotic organisms. We discuss prominent cell types involved in transducing signals from these bacteria, including epithelial cells, dendritic cells and T regulatory cells. We also draw attention to emerging data indicating interplay between the gut microbiota, enteric neurons and the immune system. There is a focus on the specific aspects of bacteria-host interactions that may influence the ability of a specific organism to confer potentially beneficial changes in immune responses. It is clear that there is still much to learn regarding the determinants of the diverse immune responses elicited by different bacterial strains by building on our current knowledge in these areas it may be possible to design clinically effective, bacteria based strategies to maintain and promote health.
Collapse
Affiliation(s)
- Paul Forsythe
- The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada
| | | |
Collapse
|
|
50
|
Molecular modulation of intestinal epithelial barrier: contribution of microbiota. J Biomed Biotechnol 2010; 2010:305879. [PMID: 20150966 PMCID: PMC2817557 DOI: 10.1155/2010/305879] [Citation(s) in RCA: 125] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2009] [Accepted: 10/28/2009] [Indexed: 12/16/2022] Open
Abstract
The daunting task required of the gut-barrier to prevent luminal pathogens and harmful substances from entering into the internal milieu and yet promoting digestion and absorption of nutrients requires an exquisite degree of coordination between the different architectural units of this barrier. The complex integration and execution of these functions are superbly carried out by the intestinal mucosal (IM) surface. Exposed to trillions of luminal microbes, the IM averts threats by signaling to the innate immune system, through pattern recognition receptors (PRR), to respond to the commensal bacteria by developing tolerance (hyporesponsiveness) towards them. This system also acts by protecting against pathogens by elaborating and releasing protective peptides, cytokines, chemokines, and phagocytic cells. The IM is constantly sampling luminal contents and making molecular adjustments at its frontier. This article describes the topography of the IM and the mechanisms of molecular adjustments that protect the internal milieu, and also describes the role of the microbiota in achieving this goal.
Collapse
|