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Shi M, Lu Y, Wu J, Zheng Z, Lv C, Ye J, Qin S, Zeng C. Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome. Int J Mol Sci 2022; 23:7595. [PMID: 35886943 PMCID: PMC9317877 DOI: 10.3390/ijms23147595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/02/2022] [Accepted: 07/06/2022] [Indexed: 02/04/2023] Open
Abstract
In recent years, many natural foods and herbs rich in phytochemicals have been proposed as health supplements for patients with metabolic syndrome (MetS). Theaflavins (TFs) are a polyphenol hydroxyl substance with the structure of diphenol ketone, and they have the potential to prevent and treat a wide range of MetS. However, the stability and bioavailability of TFs are poor. TFs have the marvelous ability to alleviate MetS through antiobesity and lipid-lowering (AMPK-FoxO3A-MnSOD, PPAR, AMPK, PI3K/Akt), hypoglycemic (IRS-1/Akt/GLUT4, Ca2+/CaMKK2-AMPK, SGLT1), and uric-acid-lowering (XO, GLUT9, OAT) effects, and the modulation of the gut microbiota (increasing beneficial gut microbiota such as Akkermansia and Prevotella). This paper summarizes and updates the bioavailability of TFs, and the available signaling pathways and molecular evidence on the functionalities of TFs against metabolic abnormalities in vitro and in vivo, representing a promising opportunity to prevent MetS in the future with the utilization of TFs.
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Affiliation(s)
- Meng Shi
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
| | - Yuting Lu
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
| | - Junling Wu
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
| | - Zhibing Zheng
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
| | - Chenghao Lv
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
| | - Jianhui Ye
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China;
| | - Si Qin
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
| | - Chaoxi Zeng
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; (M.S.); (Y.L.); (J.W.); (Z.Z.); (C.L.)
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Ishida T, Jobu K, Kawada K, Morisawa S, Kawazoe T, Shiraishi H, Fujita H, Nishimura S, Kanno H, Nishiyama M, Ogawa K, Morita Y, Hanazaki K, Miyamura M. Impact of Gut Microbiota on the Pharmacokinetics of Glycyrrhizic Acid in Yokukansan, a Kampo Medicine. Biol Pharm Bull 2022; 45:104-113. [PMID: 34980772 DOI: 10.1248/bpb.b21-00658] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Individual differences in gut microbiota can affect the pharmacokinetics of drugs. Yokukansan is a traditional Japanese kampo medicine used to treat peripheral symptoms of dementia and delirium. A study examining the pharmacokinetics of the components of yokukansan reported large individual differences in the pharmacokinetics of glycyrrhizic acid (GL). It is known that GL is metabolized by intestinal bacteria to glycyrrhetinic acid (GA), which is absorbed in the gastrointestinal tract. Thus, the gut microbiota may affect GL pharmacokinetics. We aimed to clarify the relationship between the gut microbiota composition and pharmacokinetics of GL in yokukansan. Mice were orally administered yokukansan, following the administration of various antibiotics, and the plasma concentration of GA and composition of gut microbiota were measured. The GA plasma concentration was low in mice treated with amoxicillin and vancomycin. The composition of gut microbiota revealed a different pattern from that of the control group. Mice with low plasma levels of GA had lower levels of the phylum Bacteroides and Firmicutes. Additionally, bacteria, such as those belonging to the genera Parabaceroides, Bacteroides, Ruminococcus and an unknown genus in families Lachnospiraceae and Ruminococcaceae, exerted positive correlations between the gene copies and plasma GA levels. These bacteria may contribute to the absorption of GA in the gastrointestinal tract, and multiple bacteria may be involved in GL pharmacokinetics. The pharmacokinetics of GL may be predicted by evaluating the composition of gut bacteria, rather than by evaluating the amount of a single bacterium.
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Affiliation(s)
| | - Kohei Jobu
- Department of Pharmacy, Kochi Medical School Hospital
| | - Kei Kawada
- Department of Pharmacy, Kochi Medical School Hospital.,Graduate school of Integrated Arts and Sciences, Kochi University
| | - Shumpei Morisawa
- Department of Pharmacy, Kochi Medical School Hospital.,Graduate school of Integrated Arts and Sciences, Kochi University
| | - Tetsushi Kawazoe
- Department of Pharmacy, Kochi Medical School Hospital.,Graduate school of Integrated Arts and Sciences, Kochi University
| | | | - Hiroko Fujita
- Department of Pharmacy, Kochi Medical School Hospital
| | | | - Hitomi Kanno
- Tsumura Advanced Technology Research Laboratories, Tsumura & Co
| | | | - Kazuo Ogawa
- Tsumura Advanced Technology Research Laboratories, Tsumura & Co
| | - Yasuyo Morita
- Department of Pharmacy, Kochi Medical School Hospital
| | | | - Mitsuhiko Miyamura
- Department of Pharmacy, Kochi Medical School Hospital.,Graduate school of Integrated Arts and Sciences, Kochi University
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3
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Wei HX, Wang B, Li B. IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology. Front Immunol 2020; 11:1315. [PMID: 32670290 PMCID: PMC7332769 DOI: 10.3389/fimmu.2020.01315] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 05/26/2020] [Indexed: 12/12/2022] Open
Abstract
The barrier surfaces of the gastrointestinal tract are in constant contact with various microorganisms. Cytokines orchestrate the mucosal adaptive and innate immune cells in the defense against pathogens. IL-10 and IL-22 are the best studied members of the IL-10 family and play essential roles in maintaining mucosal homeostasis. IL-10 serves as an important regulator in preventing pro-inflammatory responses while IL-22 plays a protective role in tissue damage and contributes to pathology in certain settings. In this review, we focus on these two cytokines in the development of gastrointestinal diseases, including inflammatory bowel diseases (IBD) and colitis-associated cancer (CAC). We summarize the recent studies and try to gain a better understanding on how they regulate immune responses to maintain equilibrium under inflammatory conditions.
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Affiliation(s)
- Hua-Xing Wei
- Division of Life Sciences and Medicine, Department of Laboratory Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Baolong Wang
- Division of Life Sciences and Medicine, Department of Laboratory Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Bofeng Li
- Division of Life Sciences and Medicine, Department of Medical Oncology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
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Chang CW, Chen MJ, Shih SC, Chang CW, Chiau JSC, Lee HC, Lin YS, Lin WC, Wang HY. Bacillus coagulans (PROBACI) in treating constipation-dominant functional bowel disorders. Medicine (Baltimore) 2020; 99:e20098. [PMID: 32384482 PMCID: PMC7440341 DOI: 10.1097/md.0000000000020098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 03/15/2020] [Accepted: 03/31/2020] [Indexed: 12/28/2022] Open
Abstract
Bacillus coagulans (PROBACI) bacteria have been examined for efficacy against infectious or inflammatory bowel diseases. The aim of this observational and cross-sectional study was to evaluate the effects of PROBACI against various functional bowel symptoms.Thirty-eight enrolled patients (36.5 ± 12.6 years) with functional bowel disorders in a gastrointestinal clinic were administered PROBACI (300-mg formulation containing 1 × 10 colony-forming units of B coagulans) twice/day over a 4-week period. Abdominal pain, abdominal distention, and global assessment were evaluated using a 5-point visual analog scale. The defecation characteristics, discomfort level, and effort required for defecation were recorded. The gut-microbiota composition in terms of the Firmicutes/Bacteroidetes ratio was analyzed by 16S-ribosomal RNA gene sequencing with stool samples at days 0, 14, and 28 post-treatment.The 38 patients achieved significant improvements in abdominal pain (2.8 ± 0.5 to 3.3 ± 0.7, P = .0009), abdominal distention (2.5 ± 0.7 to 3.2 ± 0.8, P = .0002), and global assessment (2.7 ± 0.6 to 3.6 ± 0.7, P = .0001) from days 0 to 14. Compared with the diarrhea group, the constipation group achieved greater improvements in terms of discomfort during defecation (2.5 ± 0.7 to 3.1 ± 0.7, P = .02) and normalization of defecation style (50% vs 7.1%, P = .007) by day 28. A difference was observed in the Firmicutes/Bacteroidetes ratio between the constipation-dominant group (118.0) and diarrhea-dominant group (319.2), but this difference was not significant.PROBACI provided control of abdominal pain, less discomfort during defecation, and a more normalized defecation style, especially in the constipation-dominant group.
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Affiliation(s)
- Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Junior College of Medicine, Nursing and Management
- MacKay Medical College, New Taipei City
| | - Ming-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Junior College of Medicine, Nursing and Management
- MacKay Medical College, New Taipei City
| | - Shou-Chuan Shih
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Medical College, New Taipei City
| | - Ching-Wei Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Junior College of Medicine, Nursing and Management
- MacKay Medical College, New Taipei City
- Institute of Traditional Medicine, National Yang-Ming University, Taipei
| | | | - Hung-Chang Lee
- Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Memorial Hospital, Hsinchu Campus
- Department of Pediatrics, Taipei Medical University, Taipei, Taiwan
| | - Yang-Sheng Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Junior College of Medicine, Nursing and Management
- MacKay Medical College, New Taipei City
| | - Wei-Chen Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Junior College of Medicine, Nursing and Management
- MacKay Medical College, New Taipei City
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus
- MacKay Junior College of Medicine, Nursing and Management
- MacKay Medical College, New Taipei City
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5
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Górska S, Sandstrőm C, Wojas-Turek J, Rossowska J, Pajtasz-Piasecka E, Brzozowska E, Gamian A. Structural and immunomodulatory differences among lactobacilli exopolysaccharides isolated from intestines of mice with experimentally induced inflammatory bowel disease. Sci Rep 2016; 6:37613. [PMID: 27869188 PMCID: PMC5116648 DOI: 10.1038/srep37613] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 11/01/2016] [Indexed: 01/01/2023] Open
Abstract
Characteristic changes in the microbiota biostructure and a decreased tolerance to intestinal bacteria have been associated with inflammatory bowel disease (IBD). However, few studies have examined the constituents of the intestinal microbiota, including the surface molecules of the bacteria, in healthy and IBD subsets. Here, we compare the chemical structures and immunomodulatory properties of the exopolysaccharides (EPS) of lactobacilli isolated from mice with induced IBD (IBD "+") versus those of healthy mice (IBD "-"). Classical structural analyses were performed using nuclear magnetic resonance spectroscopy and mass spectrometry. Immunomodulatory properties were assessed by stimulation of dendritic cells derived from mouse bone marrow or human peripheral mononuclear blood cells. Our results revealed that EPS produced by IBD "+" species are structurally different from those isolated from IBD "-". Moreover, the structurally different EPS generate different immune responses by dendritic cells. We speculate that resident strains could, upon gut inflammation, switch to producing EPS with specific motifs that are absent from lactobacilli IBD "-", and/or that bacteria with a particular EPS structure might inhabit the inflamed intestinal mucosa. This study may shed light on the role of EPS in IBD and help the development of a specific probiotic therapy for this disease.
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Affiliation(s)
- Sabina Górska
- L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
| | - Corine Sandstrőm
- Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, P. O. Box 7015, SE-750 07, Uppsala, Sweden
| | - Justyna Wojas-Turek
- L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
| | - Joanna Rossowska
- L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
| | - Elżbieta Pajtasz-Piasecka
- L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
| | - Ewa Brzozowska
- L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
| | - Andrzej Gamian
- L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
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Therapeutic effects of biobran, modified arabinoxylan rice bran, in improving symptoms of diarrhea predominant or mixed type irritable bowel syndrome: a pilot, randomized controlled study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:828137. [PMID: 25161692 PMCID: PMC4139075 DOI: 10.1155/2014/828137] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 07/05/2014] [Accepted: 07/16/2014] [Indexed: 12/15/2022]
Abstract
Background. Recently, it was revealed that low grade mucosal inflammation and/or immune imbalance of the lower digestive tract is one of the mechanisms involved in symptom generation in patients with irritable bowel syndrome (IBS). Biobran, arabinoxylan compound derived from rice bran, has been reported to have several biological actions such as anti-inflammatory and immune modulatory effects. So we investigated the therapeutic effects of Biobran in patients with IBS. Method. Forty patients with diarrhea predominant or mixed type IBS were randomly assigned to either a Biobran group for treatment with Biobran or a placebo group. Therapeutic efficacy and IBS symptoms were assessed subjectively by the patients after 4 weeks of administration. Results. The global assessment was effective in 63.2% of the Biobran group and in 30% of the placebo group (P < 0.05, Biobran group versus placebo group). Biobran group showed a significant decrease in the score of diarrhea and constipation and in CRP value. However, no significant changes were observed in the placebo group. Conclusion. The administration of Biobran improved IBS symptoms. It is likely that anti-inflammatory and/or immune modulatory effects of Biobran might be useful in IBS patients.
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7
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Oral Delivery of Glucagon Like Peptide-1 by a Recombinant Lactococcus lactis. Pharm Res 2014; 31:3404-14. [DOI: 10.1007/s11095-014-1430-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Accepted: 06/03/2014] [Indexed: 11/26/2022]
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8
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Effects of probiotic yoghurt on symptoms and intestinal microbiota in patients with irritable bowel syndrome. INT J DAIRY TECHNOL 2013. [DOI: 10.1111/1471-0307.12028] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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9
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Quigley EMM. Probiotics in the management of functional bowel disorders: promise fulfilled? Gastroenterol Clin North Am 2012; 41:805-19. [PMID: 23101688 DOI: 10.1016/j.gtc.2012.08.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Irritable bowel syndrome (IBS) and chronic constipation (CC) are common problems worldwide and are associated with significant impact on activities of daily living and quality of life. Recent interest, in IBS in particular, has focused on the potential roles of the microbiota and its interaction with the host's immune system. Recently, high-quality clinical trials have been performed on prebiotics and probiotics in IBS or CC. Although strategies that seek to modify the microbiota, such as the use of probiotics, offer much promise in IBS and CC, more high-quality trials and, studies of longer duration are required.
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Affiliation(s)
- Eamonn M M Quigley
- Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
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10
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Beena Divya J, Kulangara Varsha K, Madhavan Nampoothiri K, Ismail B, Pandey A. Probiotic fermented foods for health benefits. Eng Life Sci 2012. [DOI: 10.1002/elsc.201100179] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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11
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Jiang H, Lu Y, Yuan L, Liu J. Regulation of interleukin-10 receptor ubiquitination and stability by beta-TrCP-containing ubiquitin E3 ligase. PLoS One 2011; 6:e27464. [PMID: 22087322 PMCID: PMC3210801 DOI: 10.1371/journal.pone.0027464] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Accepted: 10/17/2011] [Indexed: 12/03/2022] Open
Abstract
Interleukin-10 (IL-10) initiates potent anti-inflammatory effects via activating its cell surface receptor, composed of IL-10R1 and IL-10R2 subunits. The level of IL-10R1 is a major determinant of the cells' responsiveness to IL-10. Here, via a series of biochemical analyses using 293T cells reconstituted with IL-10R1, we identify the latter as a novel substrate of βTrCP-containing ubiquitin E3 ligase. Within the intracellular tail of IL-10R1, a canonical (318DpSGFGpS) and a slightly deviated (369DpSGICLQEP) βTrCP recognition motif can additively recruit βTrCP in a phosphorylation-dependent manner. βTrCP recruitment leads to ubiquitination, endocytosis and degradation of IL-10R1, subsequently reducing the cellular responsiveness to IL-10. Our study uncovers a novel negative regulatory mechanism that may potentially affect IL-10 function in target cells under physiological or pathological conditions.
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Affiliation(s)
- Hui Jiang
- MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University and National Resource Center for Mutant Mice, Nanjing, China
| | - Yi Lu
- MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University and National Resource Center for Mutant Mice, Nanjing, China
| | - Liang Yuan
- MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University and National Resource Center for Mutant Mice, Nanjing, China
| | - Jianghuai Liu
- MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University and National Resource Center for Mutant Mice, Nanjing, China
- Zhejiang Key Lab for Technology & Application of Model Organisms, School of Life Science, Wenzhou Medical College, Wenzhou, China
- * E-mail:
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12
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Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation. Cell 2011; 147:629-40. [DOI: 10.1016/j.cell.2011.09.025] [Citation(s) in RCA: 583] [Impact Index Per Article: 41.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2011] [Revised: 08/15/2011] [Accepted: 09/16/2011] [Indexed: 12/11/2022]
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Faghfoori Z, Navai L, Shakerhosseini R, Somi MH, Nikniaz Z, Norouzi MF. Effects of an oral supplementation of germinated barley foodstuff on serum tumour necrosis factor-alpha, interleukin-6 and -8 in patients with ulcerative colitis. Ann Clin Biochem 2011; 48:233-7. [PMID: 21367884 DOI: 10.1258/acb.2010.010093] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The efficacy of germinated barley foodstuff (GBF) on tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and -8 (IL-8) in patients with ulcerative colitis (UC) has not yet been examined. The aim of the present study was to determine the effect of administration of GBF on serum TNF-α, IL-6 and -8 levels in UC patients in remission. METHODS Forty-one patients with UC were divided into two groups, namely control and GBF group. Twenty-one patients in the control group received standard treatment while 20 patients in the GBF group received 30 g of GBF daily by oral administration during two months of the study along with standard drug therapy. RESULTS Levels of TNF-α, IL-6 and -8 all decreased in the GBF group compared with baseline during the two-month study, while in the control group all values rose. For IL-6 and -8 this effect was significant, P = 0.034 and 0.013, respectively. CONCLUSIONS The results of the present study showed that the consumption of GBF may reduce the level of serum TNF-α, IL-6 and -8 in patients with UC. This investigation was designed as a pilot study and the results may provide a basis for more future clinical trials.
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Affiliation(s)
- Zeinab Faghfoori
- Department of Clinical Nutrition and Dietetics, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran
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Bahrami B, Macfarlane S, Macfarlane GT. Induction of cytokine formation by human intestinal bacteria in gut epithelial cell lines. J Appl Microbiol 2010; 110:353-63. [PMID: 21070518 DOI: 10.1111/j.1365-2672.2010.04889.x] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
AIMS To investigate the effects of human gut micro-organisms on cytokine production by human intestinal cell lines. METHODS AND RESULTS Quantitative real-time PCR assays were developed to measure the production of pro-inflammatory (IL-1α, IL-6, IL-18 and TNFα) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-4 and IL-10) cytokines in HT-29 and Caco-2 cell lines. They were co-cultured with a range of mucosal bacteria isolated from ulcerative colitis patients, together with lactobacilli and bifidobacteria obtained from healthy people. HT-29 cells were also co-cultured with Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli and Salmonella typhimurium. The majority of commensal bacteria tested suppressed the expression of anti-inflammatory cytokine mRNA, increased IL-18, reduced IL-1α, and with the exception of nonpathogenic E. coli, reduced TNF-α. All overtly pathogenic species increased both pro-inflammatory and anti-inflammatory cytokine mRNA. CONCLUSION Commensal and pathogenic species induced fundamentally different cytokine responses in human intestinal epithelial cell lines. SIGNIFICANCE AND IMPACT OF THE STUDY Interactions between commensal bacteria tested in this study and the innate immune system were shown to be anti-inflammatory in nature, in contrast to the pathogenic organisms investigated. These data contribute towards our understanding of how potential probiotic species can be used to suppress the pro-inflammatory response in inflammatory bowel disease.
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Affiliation(s)
- B Bahrami
- Microbiology and Gut Biology Group, University of Dundee, Dundee, UK
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Tzortzis G. Development and functional properties of Bimuno®: a second-generation prebiotic mixture. ACTA ACUST UNITED AC 2010. [DOI: 10.1616/1476-2137.15818] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Collins JK, Dunne C, Murphy L, Morrissey D, O'Mahony L, O'Sullivan E, Fitzgerald G, Kiely B, O'Sullivan GC, Daly C, Marteau P, Shanahan F. A Randomised Controlled Trial of a Probiotic Lactobacillus Strain in Healthy Adults: Assessment of its Delivery, Transit and Influence on Microbial Flora and Enteric Immunity. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2009. [DOI: 10.1080/08910600260081720] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- J. Kevin Collins
- Departments of Microbiology, Medicine and Surgery, Cork Cancer Research Centre, National Food Biotechnology Centre, University College Cork, National University of Ireland, Cork, Ireland and
| | | | | | | | | | | | | | | | | | | | - Philippe Marteau
- Service dHepato-Gastroente rologie et Endoscopies Digestives, Hopital Europe en Georges Pompidou, Paris, France
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Silk DBA, Davis A, Vulevic J, Tzortzis G, Gibson GR. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 2009; 29:508-18. [PMID: 19053980 DOI: 10.1111/j.1365-2036.2008.03911.x] [Citation(s) in RCA: 378] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). AIM To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. METHODS In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. RESULTS The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). CONCLUSION The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.
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Affiliation(s)
- D B A Silk
- Department of Academic Surgery, Imperial College Healthcare NHS Trust, London, UK.
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Eutamene H, Lamine F, Chabo C, Theodorou V, Rochat F, Bergonzelli GE, Corthésy-Theulaz I, Fioramonti J, Bueno L. Synergy between Lactobacillus paracasei and its bacterial products to counteract stress-induced gut permeability and sensitivity increase in rats. J Nutr 2007; 137:1901-7. [PMID: 17634262 DOI: 10.1093/jn/137.8.1901] [Citation(s) in RCA: 109] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Stressful events result in the alteration of gut permeability and sensitivity. Lactobacillus paracasei NCC2461 (Lpa) therapy prevents antibiotic-induced visceral hyperalgesia in mice. This study aimed at evaluating the influence of 3 probiotic strains: Bifidobacterium lactis NCC362, Lactobacillus johnsonii NCC533, and Lpa on stress-mediated alterations of colorectal hyperalgesia, on gut paracellular permeability and whether bacteria and/or bacterial products present in the spent culture medium (SCM) were involved in the antinociceptive properties of the effective strain. Rat pups were separated from their mothers 3 h/d during postnatal d 2-14. At wk 13, gut paracellular permeability was determined as a percentage of urinary excreted (51)Cr-EDTA and visceral sensitivity to colorectal distension (CRD), assessed by abdominal muscle electromyography. Visceral sensitivity was also analyzed in adults rats subjected to partial restraint stress (PRS, 2 h restriction of body movements). Rats received either the probiotics resuspended in SCM or fresh growth medium as control for 2 wk. Maternal deprivation significantly increased colonic sensitivity in response to CRD and enhanced gut paracellular permeability compared with control rats. Only Lpa treatment significantly improved stress-induced visceral pain and restored normal gut permeability. Similarly, among the 3 probiotics tested, only Lpa prevented PRS-mediated visceral hyperalgesia. Both bacteria and bacterial products present in Lpa SCM were required for the antinociceptive properties against PRS. This study illustrates strain-specific effects and suggests a synergistic interplay between L. paracasei bacteria and bacterial products generated during fermentation and growth that confers the ability to suppress PRS-induced hypersensitivity in rats.
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Affiliation(s)
- Hélène Eutamene
- Neuro-Gastroenterology and Nutrition Unit, UMR 1054 INRA/ EI-Purpan, Toulouse, France
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19
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Hayes M, Ross RP, Fitzgerald GF, Stanton C. Putting microbes to work: Dairy fermentation, cell factories and bioactive peptides. Part I: Overview. Biotechnol J 2007; 2:426-34. [PMID: 17407210 DOI: 10.1002/biot.200600246] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
A variety of milk-derived biologically active peptides have been shown to exert both functional and physiological roles in vitro and in vivo, and because of this are of particular interest for food science and nutrition applications. Biological activities associated with such peptides include immunomodulatory, antibacterial, anti-hypertensive and opioid-like properties. Milk proteins are recognized as a primary source of bioactive peptides, which can be encrypted within the amino acid sequence of dairy proteins, requiring proteolysis for release and activation. Fermentation of milk proteins using the proteolytic systems of lactic acid bacteria (LAB) is an attractive approach for generation of functional foods enriched in bioactive peptides given the low cost and positive nutritional image associated with fermented milk drinks and yoghurt. In this review, we discuss the exploitation of such fermentation towards the development of functional foods conferring specific health benefits to the consumer beyond basic nutrition. In particular, in Part I, we focus on the release of encrypted bioactive peptides from a range of food protein sources, as well as the use of LAB as cell factories for the de novo generation of bioactivities.
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Affiliation(s)
- Maria Hayes
- Teagasc, Moorepark Food Research Centre, Fermoy, Co. Cork, Ireland.
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20
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Abstract
Neonatal necrotizing enterocolitis is the second most common cause of morbidity in premature infants and requires intensive care over an extended period. Despite advances in medical and surgical techniques, the mortality and long-term morbidity due to necrotizing enterocolitis remain very high. Recent advances have shifted the attention of researchers from the classic triad (ischemia, bacteria, and the introduction of a metabolic substrate into the intestine) of necrotizing enterocolitis, to gut maturation, feeding practices, and inflammation. The focus on inflammation includes proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-18, and platelet-activating factor. Research related to the etiology of necrotizing enterocolitis has moved quickly from clostridial toxin to bacterial and other infectious agents. More recently, the pattern of bacterial colonization has been given emphasis rather than the particular species or strain of bacteria or their virulence. Gram-negative bacteria that form part of the normal flora are now speculated as important factors in triggering the injury process in a setting where there is a severe paucity of bacterial species and possible lack of protective Gram-positive organisms. Although the incidence of necrotizing enterocolitis has increased because of the survival of low birthweight infants, clinicians are more vigilant in their detection of the early gastrointestinal symptoms of necrotizing enterocolitis; however, radiographic demonstration of pneumatosis intestinalis remains the hallmark of necrotizing enterocolitis. With prompt diagnosis, a large proportion of infants with necrotizing enterocolitis are now able to be managed medically with intravenous fluid and nutrition, nasogastric suction, antibacterials, and close monitoring of physiologic parameters. In the advanced cases that require surgery, clinicians tend to opt for either simple peritoneal drainage (for very small and sick infants) or laparotomy and resection of the affected part. Intestinal transplantation later in life is available as a viable option for those who undergo resection of large segments of the intestine. It is becoming more evident that treatment of this devastating disease is expensive and comes with the toll of significant long-term sequelae. This has resulted in renewed interest in designing alternative strategies to prevent this serious gastrointestinal disease. Simple trophic feeding and the use of L-glutamine and arginine are novel avenues that have been examined. The use of probiotics ('friendly' bacterial flora) has been introduced as a promising tool for establishing healthy bacterial flora in the newborn gut to block the injury process that may ultimately lead to necrotizing enterocolitis.
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Affiliation(s)
- Pinaki Panigrahi
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA.
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21
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Keohane J, Sibartie S, Shanahan F. Probiotics in Inflammatory Bowel Disease. SEMINARS IN COLON AND RECTAL SURGERY 2006. [DOI: 10.1053/j.scrs.2006.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Kanauchi O, Fukuda M, Matsumoto Y, Ishii S, Ozawa T, Shimizu M, Mitsuyama K, Andoh A. Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity. World J Gastroenterol 2006; 12:1071-7. [PMID: 16534848 PMCID: PMC4087899 DOI: 10.3748/wjg.v12.i7.1071] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To examine the effect of Eubacterium limosum (E.limosum) on colonic epithelial cell line in vitro, and to evaluate the effect of E.limosum on experimental colitis.
METHODS: E.limosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E.limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 (TLR4) was evaluated by real time PCR. Colitis was induced by feeding BALB/C mice with 2.0% dextran sodium sulfate. These mice received either 5% lyophilized E.limosum (n = 7) or control diet (n = 7). Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.
RESULTS: The E.limosum produced butyrate, acetate, propionate, and lactate at 0.25, 1.0, 0.025 and 0.07 mmol/L, respectively in medium. At this concentration, each acid had no growth stimulating activity on T84 cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1 mmol/L. In addition, under TNF-α stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E.limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.
CONCLUSION: E.limosum can ameliorate experimental colonic inflammation. In part, the metabolite of E.limosum, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.
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Affiliation(s)
- Osamu Kanauchi
- Kirin Brewery Co. Ltd., 10-1-2 Shinkawa Chuo-ku, Tokyo 104-8288, Japan.
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23
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Affiliation(s)
- Eamonn M M Quigley
- Alimentary Pharmabiotic Center, National University of Ireland, Department of Medicine, Cork University Hospital, Clinical Sciences Building, Cork, Ireland.
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24
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de Vos WM. Lipotechoic acid in lactobacilli: D-alanine makes the difference. Proc Natl Acad Sci U S A 2005; 102:10763-4. [PMID: 16046536 PMCID: PMC1182463 DOI: 10.1073/pnas.0504966102] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Willem M de Vos
- Laboratory of Microbiology and Wageningen Centre for Food Sciences, Hesselink van Suchtelenweg 4, 6703 CT Wageningen, The Netherlands
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25
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Candela M, Seibold G, Vitali B, Lachenmaier S, Eikmanns BJ, Brigidi P. Real-time PCR quantification of bacterial adhesion to Caco-2 cells: competition between bifidobacteria and enteropathogens. Res Microbiol 2005; 156:887-95. [PMID: 16024231 DOI: 10.1016/j.resmic.2005.04.006] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2005] [Revised: 04/14/2005] [Accepted: 04/26/2005] [Indexed: 11/15/2022]
Abstract
Probiotic bacteria play an important role in protecting the host from intestinal colonization of pathogenic bacteria. We have developed a new analytical approach based on a real-time PCR technique for quantifying Bifidobacterium adhesion to intestinal epithelial cells. Real-time PCR analysis showed that adhesion to enterocyte-like Caco-2 cells represented a variable phenotype in the genus Bifidobacterium, enabling classification of three adhesion behaviors: high adhesiveness (>40 bifidobacterial cells/Caco-2 cell); adhesiveness (5-40 bifidobacterial cells/Caco-2 cell); no adhesiveness (<5 bifidobacterial cells/Caco-2 cell). This molecular methodology was successfully used in competition studies in enteropathogens. All bifidobacterial strains examined evidenced displacement activity towards important enteropathogens (S. typhimurium, Y. enterocolitica and E. coli EPEC). Real-time PCR is a rapid, accurate and sensitive method for detecting and quantifying different bacterial genera and species simultaneously adhering to a epithelial cell monolayer.
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Affiliation(s)
- Marco Candela
- Department of Pharmaceutical Sciences, CIRB-Center for Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy
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26
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Kesisoglou F, Zimmermann EM. Novel drug delivery strategies for the treatment of inflammatory bowel disease. Expert Opin Drug Deliv 2005; 2:451-63. [PMID: 16296767 DOI: 10.1517/17425247.2.3.451] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Inflammatory bowel disease (IBD) encompasses two idiopathic inflammatory diseases of the intestinal tract: Crohn's disease and ulcerative colitis. Existing therapy for IBD consists mainly of orally or rectally administered small drug molecules, such as 5-aminosalicylates and corticosteroids, or potent systemic immune suppressants. IBD presents a challenging target for drug delivery, particularly by the oral route, as, contrary to most therapeutic regimens, minimal systemic absorption and maximal intestinal wall drug levels are desired. Several delivery strategies are employed to achieve this goal, including the chemical modification of the drug molecules, the use of controlled- and delayed-release formulations and the use of bioadhesive particles. The goal of this review is to summarise existing IBD therapy and examine novel approaches in intestinal drug delivery.
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Affiliation(s)
- Filippos Kesisoglou
- University of Michigan Department of Pharmaceutical Sciences, College of Pharmacy, Ann Arbor, MI 48109-1065, USA
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27
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Thompson-Chagoyán OC, Maldonado J, Gil A. Aetiology of inflammatory bowel disease (IBD): role of intestinal microbiota and gut-associated lymphoid tissue immune response. Clin Nutr 2005; 24:339-52. [PMID: 15896420 DOI: 10.1016/j.clnu.2005.02.009] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2005] [Accepted: 02/21/2005] [Indexed: 01/01/2023]
Abstract
The aetiology of inflammatory bowel disease (IBD) probably involves a combination of genetic predisposition and environmental factors that may be channelled through an abnormality in gut-barrier function, with a loss of antigen tolerance. Some genetic markers that predispose to inflammatory disease have been identified (alleles DR2, DRB1*0103, DRB1*12 and mutations in the NOD2/CARD15 gene on chromosome 16). Alterations in the pattern of cytokine production by T cell subclasses leading to loss of tolerance to oral antigens have been documented. Moreover, a number of environmental factors (cigarette smoking, use of non-steroid anti-inflammatory drugs, psychological stress and the presence of the caecal appendix) have been postulated as a trigger of IBD. It has also been suggested that the gut microbiota plays a major role in the development and persistence of IBD, and numerous modifications of intestinal microbiota composition have been identified. As a result, manipulation of the microbiota with antibiotics is a current therapeutic strategy; more recently, however, a number of studies have reported promising results when using probiotic organisms to manipulate gut microbiota composition in order to restore tolerance to microbial antigens of the host's own microbiota.
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Affiliation(s)
- Oscar C Thompson-Chagoyán
- Department of Paediatrics, Los Venados General Hospital, Mexican Institute of Social Security, México City, México
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28
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Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling. Infect Immun 2005. [PMID: 15731043 DOI: 10.1128/iai.73.3.1452-1465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor alpha, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis.
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29
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Sturm A, Rilling K, Baumgart DC, Gargas K, Abou-Ghazalé T, Raupach B, Eckert J, Schumann RR, Enders C, Sonnenborn U, Wiedenmann B, Dignass AU. Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling. Infect Immun 2005; 73:1452-65. [PMID: 15731043 PMCID: PMC1064918 DOI: 10.1128/iai.73.3.1452-1465.2005] [Citation(s) in RCA: 101] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor alpha, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis.
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Affiliation(s)
- Andreas Sturm
- Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
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30
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O'Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, O'Sullivan GC, Kiely B, Collins JK, Shanahan F, Quigley EMM. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005; 128:541-51. [PMID: 15765388 DOI: 10.1053/j.gastro.2004.11.050] [Citation(s) in RCA: 953] [Impact Index Per Article: 47.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome (IBS) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain. METHODS Seventy-seven subjects with IBS were randomized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624, each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink, or the malted milk drink alone as placebo for 8 weeks. The cardinal symptoms of IBS were recorded on a daily basis and assessed each week. Quality of life assessment, stool microbiologic studies, and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase. RESULTS For all symptoms, with the exception of bowel movement frequency and consistency, those randomized to B infantis 35624 experienced a greater reduction in symptom scores; composite and individual scores for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty were significantly lower than for placebo for those randomized to B infantis 35624 for most weeks of the treatment phase. At baseline, patients with IBS demonstrated an abnormal IL-10/IL-12 ratio, indicative of a proinflammatory, Th-1 state. This ratio was normalized by B infantis 35624 feeding alone. CONCLUSIONS B infantis 35624 alleviates symptoms in IBS; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine, suggesting an immune-modulating role for this organism, in this disorder.
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Affiliation(s)
- Liam O'Mahony
- Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
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31
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Reid G. When microbe meets human. Clin Infect Dis 2004; 39:827-30. [PMID: 15472815 DOI: 10.1086/423387] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2004] [Accepted: 05/11/2004] [Indexed: 11/03/2022] Open
Abstract
Microbes make up a significant component of the human body, yet relatively little is known about how they influence health and disease. They colonize after birth by chance and circumstance, yet play a major role in immunity, digestion, and protection against disease. In relatively recent times, basic science and clinical studies have clearly shown the potential impact of indigenous and exogenous microbes on human health and well-being. Yet regulatory bodies, research funding agencies, and health care practitioners, perhaps disillusioned by too many unreliable, overhyped products that are marketed under the guise of probiotics or natural therapeutics, have lagged far behind in embracing this avenue of enquiry. As more scientifically proven probiotic products differentiate themselves from untested and unproven cure-alls, and as multidisciplinary research groups piece together the diverse components of the puzzle, humans will slowly begin to understand how best to optimize their coexistence with microbial organisms, thus perhaps prolonging and enhancing life.
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Affiliation(s)
- Gregor Reid
- Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, London, Ontario, Canada.
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Affiliation(s)
- Fergus Shanahan
- Alimentary Pharmabiotic Centre and Department of Medicine, National University of Ireland. Cork
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Shanahan F. Probiotics in inflammatory bowel disease--therapeutic rationale and role. Adv Drug Deliv Rev 2004; 56:809-18. [PMID: 15063591 DOI: 10.1016/j.addr.2003.11.003] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2003] [Accepted: 11/03/2003] [Indexed: 12/13/2022]
Abstract
The intestinal flora has a conditioning effect on intestinal homeostasis, delivering regulatory signals to the epithelium, the mucosal immune system and to the neuromuscular activity of the gut. Beneficial metabolic activities of the enteric flora include nutrient production, metabolism of dietary carcinogens, conversion of prodrugs to active drugs. However, increasing evidence suggests that some components of the enteric flora are essential ingredients in the pathogenesis of inflammatory bowel disease (IBD); this has prompted interest in therapeutic manipulation of the flora with probiotics. Probiotics are biologic control agents-described as live microbial food supplements which confer a health benefit beyond inherent basic nutrition. Multiple potential beneficial effects have been attributed to the probiotic use of lactic acid bacteria, bifidobacteria and other non-pathogenic commensals. At present, much of the promise of probiotics remains outside the realm of evidence-based medicine and awaits the results of prospective trials, now underway. No reliable in vitro predictors of in vivo efficacy of putative probiotics have been identified. Rigorous comparisons of probiotic performance have not been performed and the suitability of a given probiotic for different individuals is largely unexplored. Notwithstanding, an improved understanding of the normal commensal flora and host-flora interactions has the potential to open up new therapeutic strategies for inflammatory disorders of the gut.
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Affiliation(s)
- Fergus Shanahan
- Alimentary Pharmabiotic Centre, Department of Medicine, Clinical Science Building, Cork University Hospital, University College Cork, National University of Ireland, Wilton, Cork, Ireland.
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Zuleta A, Sarchi MI, Rio ME, Sambucetti ME. Fermented milk-starch and milk-inulin products as vehicles for lactic acid bacteria. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2004; 59:155-160. [PMID: 15678724 DOI: 10.1007/s11130-004-0048-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Formulations using cassava starch or inulin plus milk were fermented with three different lactic acid bacteria (LAB) strains: Lactobacillus plantarum D34, Lactobacillus sp. SLH6, and Streptococcus thermophilus ST4. Growth and acidification were followed in 3% powdered milk (M3), 3% milk-6% starch (M3-S6), and 3% milk-6% inulin (M3-In6). D34 and SLH6 growth was enhanced by starch in M3-S6, when compared to the count (CFU/ml) obtained in M3. Growth of all strains was promoted by inulin. All fermented products showed LAB counts of 8.0 log or higher. Carbohydrate utilization was in agreement with growth and acidification results. The highest increase in CFU in rat feces was observed in M3-S6 fermented with ST4; the D34 fermented product also increased CFU but SLH6 did not, either with starch or inulin. This suggests that ST4 and D34 strains provide a good choice to ferment the proposed formulations in order to obtain a marked improvement of natural intestinal flora.
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Affiliation(s)
- Angela Zuleta
- Facultad de Farmacía y Bioquímica, Universidad de Buenos Aires, Junin 956, (1113) Buenos Aires, Argentina
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Abstract
Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. There is now mounting evidence that selected probiotic strains can provide health benefits to their human hosts. Numerous clinical trials show that certain strains can improve the outcome of intestinal infections by reducing the duration of diarrhea. Further investigations have shown benefits in reducing the recurrence of urogenital infections in women, while promising studies in cancer and allergies require research into the mechanisms of activity for particular strains and better-designed trials. At present, only a small percentage of physicians either know of probiotics or understand their potential applicability to patient care. Thus, probiotics are not yet part of the clinical arsenal for prevention and treatment of disease or maintenance of health. The establishment of accepted standards and guidelines, proposed by the Food and Agriculture Organization of the United Nations and the World Health Organization, represents a key step in ensuring that reliable products with suitable, informative health claims become available. Based upon the evidence to date, future advances with single- and multiple-strain therapies are on the horizon for the management of a number of debilitating and even fatal conditions.
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Affiliation(s)
- Gregor Reid
- Canadian Research and Development Centre for Probiotics, The Lawson Health Research Institute, London, Ontario N6A 4V2, Canada.
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36
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Marteau P, Shanahan F. Basic aspects and pharmacology of probiotics: an overview of pharmacokinetics, mechanisms of action and side-effects. Best Pract Res Clin Gastroenterol 2003; 17:725-40. [PMID: 14507584 DOI: 10.1016/s1521-6918(03)00055-6] [Citation(s) in RCA: 107] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Probiotics have been defined as non-pathogenic micro-organisms that, when ingested, exert a positive influence on host health or physiology. Their pharmacology is more complex than that of inert drugs but is now being studied in detail. Some strains have a high survival capacity until they reach the faeces, whereas others are rapidly killed by acid and bile (a characteristic that can be used for the delivery of active intracellular components). Potential translocation and permanent colonization are rare but possible events; and should come under closer scrutiny. Mechanisms of action can be direct or indirect through modifications of the endogenous flora or through immunomodulation. The active components are poorly known but include bacterial formylated peptides, peptidoglycan cell wall constituents and nucleotides. Although the safety of commercial probiotics is excellent, this aspect should be studied in more detail, especially in immunocompromised hosts.
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Affiliation(s)
- Philippe Marteau
- Department of Gastroenterology, European Hospital Georges Pompidou, Assistance Publique des Hôpitaux de Paris and Paris V University, France.
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37
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Lammers KM, Brigidi P, Vitali B, Gionchetti P, Rizzello F, Caramelli E, Matteuzzi D, Campieri M. Immunomodulatory effects of probiotic bacteria DNA: IL-1 and IL-10 response in human peripheral blood mononuclear cells. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 2003; 38:165-72. [PMID: 13129651 DOI: 10.1016/s0928-8244(03)00144-5] [Citation(s) in RCA: 186] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
A new therapeutic approach for inflammatory bowel diseases is based on the administration of probiotic bacteria. Prokaryotic DNA contains unmethylated CpG motifs which can activate immune responses, but it is unknown whether bacterial DNA is involved in the beneficial effects obtained by probiotic treatment. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with pure DNA of eight probiotic strains and with total bacterial DNA from human feces collected before and after probiotic ingestion. Cytokine production was analyzed in culture supernatants. Modification of human microflora after probiotic administration was proven by polymerase chain reaction analysis. Here we show that Bifidobacterium genomic DNA induced secretion of the antiinflammatory interleukin-10 by PBMC. Total bacterial DNA from feces collected after probiotic administration modulated the immune response by a decrease of interleukin-1 beta and an increase of interleukin-10.
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Affiliation(s)
- Karen Manon Lammers
- Department of Internal Medicine and Gastroenterology, University of Bologna, Policlinic S. Orsola, Via Massarenti 9, 40138 Bologna, Italy.
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38
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Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, Ogura Y, Kawasaki A, Fukase K, Kusumoto S, Valvano MA, Foster SJ, Mak TW, Nuñez G, Inohara N. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 2003; 4:702-7. [PMID: 12796777 DOI: 10.1038/ni945] [Citation(s) in RCA: 943] [Impact Index Per Article: 42.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2003] [Accepted: 05/22/2003] [Indexed: 12/29/2022]
Abstract
Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan.
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Affiliation(s)
- Mathias Chamaillard
- Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
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Abstract
We urgently need animal models to study infectious disease. Mice are susceptible to a similar range of microbial infections as humans. Marked differences between inbred strains of mice in their response to pathogen infection can be exploited to analyse the genetic basis of infections. In addition, the genetic tools that are available in the laboratory mouse, and new techniques to monitor the expression of bacterial genes in vivo, make it the principal experimental animal model for studying mechanisms of infection and immunity.
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Affiliation(s)
- Jan Buer
- German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany
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40
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Glück U, Gebbers JO. Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic streptococci). Am J Clin Nutr 2003; 77:517-20. [PMID: 12540416 DOI: 10.1093/ajcn/77.2.517] [Citation(s) in RCA: 118] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND As a bacterial reservoir, the nose may harbor potentially pathogenic bacteria (PPB: Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci, and Haemophilus influenzae). In patients carrying PPB, antiseptic regimens could be crucial for infection control after major operations on or injuries of the head, nasal sinuses, or lungs. Such regimens may also be important for diabetic patients and persons receiving hemodialysis, in intensive care units, or with impaired immunity due to various other causes. OBJECTIVE We tested a possible effect of the ingestion of probiotics on the bacterial flora of the nose. DESIGN In an open, prospective trial, 209 volunteers were randomly assigned to consume either a probiotic, fermented milk drink [65 mL with Lactobacillus GG (ATCC 53103), Bifidobacterium sp B420, Lactobacillus acidophilus 145, and Streptococcus thermophilus; n = 108] or standard yogurt (180 g; n = 101) daily for 3 wk. Nasal microbial flora were analyzed on days 1, 21, and 28. The microbial examination was blinded to the source of the samples. RESULTS We found a significant reduction (19%; P < 0.001) in the occurrence of nasal PPB in the group who consumed the probiotic drink but not in the group who consumed yogurt. The effect was mainly on gram-positive bacteria, which decreased significantly (P < 0.05). CONCLUSIONS The results indicate that regular intake of probiotics can reduce PPB in the upper respiratory tract. The results also indicate a linkage of the lymphoid tissue between the gut and the upper respiratory tract.
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Affiliation(s)
- Ulrich Glück
- Suva, Swiss National Accident Insurance Institute, Division of Occupational Medicine, Lucerne, Switzerland.
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Marteau P, Seksik P, Shanahan F. Manipulation of the bacterial flora in inflammatory bowel disease. Best Pract Res Clin Gastroenterol 2003; 17:47-61. [PMID: 12617882 DOI: 10.1053/bega.2002.0344] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
In this chapter we summarize the clinical and experimental data which indicate that bacteria, especially from the endogenous microflora, play a role in the pathogenesis of Crohn's disease, ulcerative colitis and pouchitis. We review the clinical trials, focusing on randomized controlled trials which used antibiotics or probiotics to treat situations of IBD or prevent recurrence, and we discuss the future of this approach.
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Affiliation(s)
- Philippe Marteau
- Gastroenterology Department, European Hospital Georges Pompidou, AP-HP & Paris V University, France
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Schultz M, Schölmerich J, Rath HC. Rationale for probiotic and antibiotic treatment strategies in inflammatory bowel diseases. Dig Dis 2003; 21:105-28. [PMID: 14571109 DOI: 10.1159/000073243] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Inflammatory bowel diseases (IBD), commonly referred to as Crohn's disease and ulcerative colitis are chronic aggressive disorders which share many similarities concerning pathomechanism and clinical course, but have very distinct features. Both entities are mainly located in areas with high bacterial concentrations, such as the terminal ileum and cecum in Crohn's disease and the rectum in ulcerative colitis. In recent years, overwhelming evidence accumulated, supporting the hypothesis that IBD are characterized by a genetically determined, overly aggressive immune response towards ubiquitous luminal antigens, especially commensal bacteria and their products. Trials in both human IBD and experimental colitis have demonstrated that broad-spectrum antibiotics may influence the course of ulcerative colitis and Crohn's disease and antibiotics with narrow activity against the anaerobic fraction of the flora can prevent relapse in Crohn's disease after surgically induced remission. Since relevant antibiotic strategies can be associated with some side effects, the ongoing research recently focused on alternative methods to modify the intestinal flora in patients with IBD. Clinical observations including few controlled trials, basic research, and animal studies have suggested a potential role for probiotic bacteria within the treatment regimens for IBD. However, the mode of action of these organisms is still largely unclear and in vitro studies are inconclusive. This review summarizes recent in vitro and in vivo data regarding the role of the intestinal microflora in the pathogenesis of chronic intestinal inflammation and possible therapeutic mechanisms of probiotic bacteria relevant to IBD. Furthermore, we will review clinical trials examining the efficacy of antibiotic and probiotic treatment strategies in IBD.
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Affiliation(s)
- Michael Schultz
- Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
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43
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Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem 2002; 277:50959-65. [PMID: 12393915 PMCID: PMC4006994 DOI: 10.1074/jbc.m207050200] [Citation(s) in RCA: 377] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Probiotic bacteria are microorganisms that benefit the host by preventing or ameliorating disease. However, little information is known regarding the scientific rationale for using probiotics as alternative medicine. The purpose of this paper is to investigate the mechanisms of probiotic beneficial effects on intestinal cell homeostasis. We now report that one such probiotic, Lactobacillus rhamnosus GG (LGG), prevents cytokine-induced apoptosis in two different intestinal epithelial cell models. Culture of LGG with either mouse or human colon cells activates the anti-apoptotic Akt/protein kinase B. This model probiotic also inhibits activation of the pro-apoptotic p38/mitogen-activated protein kinase by tumor necrosis factor, interleukin-1alpha, or gamma-interferon. Furthermore, products recovered from LGG culture broth supernatant show concentration-dependent activation of Akt and inhibition of cytokine-induced apoptosis. These observations suggest a novel mechanism of communication between probiotic microorganisms and epithelia that increases survival of intestinal cells normally found in an environment of pro-apoptotic cytokines.
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Affiliation(s)
- Fang Yan
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| | - D. Brent Polk
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Department of Cell and Developmental Biology, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- To whom correspondence should be addressed: Pediatric Gastroenterology, Hepatology, and Nutrition, S4322 MCN, 21st and Garland Ave., Nashville, TN 37232-2576. Tel.: 615-322-7449; Fax: 615-343-8915;
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44
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Abstract
Colonization with bacteria is critical for the normal structural and functional development and optimal function of the mucosal immune system. Unrestrained mucosal immune activation in response to bacterial signals from the lumen is, however, a risk factor for inflammatory bowel disease. Therefore, mucosal immune responses to indigenous flora require precise control and an immunosensory capacity for distinguishing commensals from pathogens. The use of germ-free animal models with selective colonization strategies combined with modern molecular techniques promises to clarify the molecular signals responsible for host-flora interactions in health and disease. At least half of the resident flora cannot be cultured by conventional techniques but are identifiable by molecular methods. Collectively, the resident flora represent a virtual organ with a metabolic activity in excess of the liver and a microbiome in excess of the human genome. An improved understanding of this hidden organ holds secrets relevant to several infectious, inflammatory and neoplastic disease mechanisms.
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Affiliation(s)
- Fergus Shanahan
- Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland
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45
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Mitsuyama K, Toyonaga A, Sata M. Intestinal microflora as a therapeutic target in inflammatory bowel disease. J Gastroenterol 2002; 37 Suppl 14:73-7. [PMID: 12572870 DOI: 10.1007/bf03326418] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Although the causes of inflammatory bowel disease (IBD) remain incompletely understood, increasing evidence implicates intestinal microflora in the pathogenesis of these disorders. Alteration of intestinal flora therefore may offer a plausible therapeutic approach. Although recent data support a potential therapeutic role for probiotics and prebiotics in patients with IBD, such treatments need to be further assessed by large, double-blind controlled trials. A better understanding of the intestinal microflora and the mechanisms of their action may help us to develop more effective treatment for IBD.
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Affiliation(s)
- Keiichi Mitsuyama
- Second Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
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46
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Reid G, Charbonneau D, Erb J, Poehner R, Gonzalez S, Gardiner G, Bruce AW. Ability of Lactobacillus GR-1 and RC-14 to Stimulate Host Defences and Reduce Gut Translocation and Infectivity of Salmonella typhimurium. Prev Nutr Food Sci 2002. [DOI: 10.3746/jfn.2002.7.2.168] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Abstract
An unsolved puzzle in IBD research is whether germs, genes, or a combination of the two with excessive immune responses to gut-associated bacteria explains the pathogenesis of UC and CD. Whatever the answer, there is little doubt that microbial factors are involved intimately in IBD pathogenesis. Although a long search has failed to confirm a direct pathogenic role for a specific infectious agent, compelling evidence suggests that commensal enteric bacteria and their products provide a local environmental trigger that initiates and perpetuates IBD, reactivates quiescent disease, results in the frequent septic complications of CD, and contributes to the development of several extraintesinal manifestations. The most compelling evidence for involvement of the enteric flora in the pathogenesis of IBD has been generated from studies of animal models, which collectively support the view that IBD is due to genetically determined dysregulation of the mucosal immune response to luminal antigens derived from the normal bacterial flora. Although removing or dampening the dominant antigenic stimuli with antibiotics or probiotics is conceptually superior to the current array of immunosuppressive and anti-inflammatory agents that nonspecifically block the inflammatory cascade, more definitive, rigorously designed, controlled trials of treatments directed at the microflora are needed. Future research investigating mechanisms of tolerance to luminal bacteria and an understanding of how probiotics can manipulate the intestinal flora beneficially will bring clinicians closer to identifying potential therapeutic targets and unraveling the bacterial connection to IBD pathogenesis.
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Affiliation(s)
- Richard J Farrell
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Dana 501, 330 Brookline Avenue, Boston, MA 02115, USA.
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48
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Abstract
Crohn's disease is a disorder mediated by T lymphocytes which arises in genetically susceptible individuals as a result of a breakdown in the regulatory constraints on mucosal immune responses to enteric bacteria. Regulation of immune reactivity to enteric antigens has improved understanding of the pathophysiological mechanisms of Crohn's disease, and has expanded therapeutic options for patients with this disorder. Disease heterogeneity is probable, with various underlying defects associated with a similar pathophysiological outcome. Although most conventional drug treatments are directed at modification of host response, therapeutic manipulation of the enteric flora is becoming a realistic option.
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Affiliation(s)
- Fergus Shanahan
- Department of Medicine, Clinical Sciences Building, Cork University Hospital, Cork, Ireland.
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Christensen HR, Frøkiaer H, Pestka JJ. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2002; 168:171-8. [PMID: 11751960 DOI: 10.4049/jimmunol.168.1.171] [Citation(s) in RCA: 620] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Dendritic cells (DC) play a pivotal immunoregulatory role in the Th1, Th2, and Th3 cell balance and are present throughout the gastrointestinal tract. Thus, DC may be targets for modulation by gut microbes, including ingested probiotics. In the present study, we tested the hypothesis that species of Lactobacillus, important members of the gut flora, differentially activate DC. Bone marrow-derived murine DC were exposed to various lethally irradiated Lactobacillus spp. and resultant culture supernatants were analyzed for IL-6, IL-10, IL-12, and TNF-alpha. Substantial differences were found among strains in the capacity to induce IL-12 and TNF-alpha production in the DC. Similar but less pronounced differences were observed among lactobacilli in the induction of IL-6 and IL-10. Although all strains up-regulated surface MHC class II and B7-2 (CD86), which is indicative of DC maturation, those lactobacilli with greatest capacity to induce IL-12 were most effective. Remarkably, Lactobacillus reuteri DSM12246, a poor IL-12 inducer, inhibited IL-12, IL-6, and TNF-alpha induction by the otherwise strong cytokine inducer L. casei CHCC3139, while IL-10 production remained unaltered. In analogous fashion, L. reuteri reduced L. casei-induced up-regulation of B7-2. These results suggest that different species of Lactobacillus exert very different DC activation patterns and, furthermore, at least one species may be capable of inhibiting activities of other species in the genus. Thus, the potential exists for Th1/Th2/Th3-driving capacities of the gut DC to be modulated according to composition of gut microflora, including ingested probiotics.
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Affiliation(s)
- Hanne R Christensen
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA
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50
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