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Oh HN, Shin SY, Kim JH, Baek J, Kim HJ, Lee KM, Park SJ, Kim SY, Choi HK, Kim W, Sul WJ, Choi CH. Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets. Gut Pathog 2024; 16:44. [PMID: 39187879 PMCID: PMC11346184 DOI: 10.1186/s13099-024-00637-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 08/16/2024] [Indexed: 08/28/2024] Open
Abstract
BACKGROUND While significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC). RESULTS The microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851). CONCLUSIONS The gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.
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Affiliation(s)
- Han Na Oh
- Department of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea
- Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, Republic of Korea
| | - Seung Yong Shin
- Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-Ro, Dongjak-Gu, Seoul, Republic of Korea, 06973
| | - Jong-Hwa Kim
- Department of Microbiology, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Jihye Baek
- Department of Microbiology, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Hyo Jong Kim
- Department of Gastroenterology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Kang-Moon Lee
- Department of Gastroenterology, The Catholic University of Korea St. Vincent's Hospital, Suwon, Republic of Korea
| | - Soo Jung Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seok-Young Kim
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - Hyung-Kyoon Choi
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - Wonyong Kim
- Department of Microbiology, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Woo Jun Sul
- Department of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea.
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-Ro, Dongjak-Gu, Seoul, Republic of Korea, 06973.
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Ryu HM, Islam SMS, Riaz B, Sayeed HM, Choi B, Sohn S. Immunomodulatory Effects of a Probiotic Mixture: Alleviating Colitis in a Mouse Model through Modulation of Cell Activation Markers and the Gut Microbiota. Int J Mol Sci 2024; 25:8571. [PMID: 39201260 PMCID: PMC11354276 DOI: 10.3390/ijms25168571] [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: 07/12/2024] [Revised: 08/02/2024] [Accepted: 08/02/2024] [Indexed: 09/02/2024] Open
Abstract
Ulcerative colitis (UC) is a persistent inflammatory intestinal disease that consistently affects the colon and rectum. Its exact cause remains unknown. UC causes a considerable challenge in healthcare, prompting research for novel therapeutic strategies. Although probiotics have gained popularity as possible candidates for managing UC, studies are still ongoing to identify the best probiotics or probiotic mixtures for clinical applications. This study aimed to determine the efficacy of a multi-strain probiotic mixture in mitigating intestinal inflammation in a colitis mouse model induced by dextran sulfate sodium. Specifically, a multi-strain probiotic mixture consisting of Tetragenococcus halophilus and Eubacterium rectale was used to study its impact on colitis symptoms. Anti-inflammatory effects were evaluated using ELISA and flow cytometry. The configuration of gut microbial communities was determined using 16S rRNA metagenomic analysis. According to this study, colitis mice treated with the probiotic mixture experienced reduced weight loss and significantly less colonic shortening compared to untreated mice. Additionally, the treated mice exhibited increased levels of forkhead box P3 (Foxp3) and interleukin 10, along with decreased expression of dendritic cell activation markers, such as CD40+, CD80+, and CD83+, in peripheral blood leukocytes and intraepithelial lymphocytes. Furthermore, there was a significant decrease in the frequencies of CD8+N.K1.1+ cells and CD11b+Ly6G+ cells. In terms of the gut microbiota, probiotic-mixture treatment of colitis mice significantly increased the abundance of the phyla Actinobacteria and Verrucomicrobia (p < 0.05). These results provide valuable insights into the therapeutic promise of multi-strain probiotics, shedding light on their potential to alleviate colitis symptoms. This research contributes to the ongoing exploration of effective probiotic interventions for managing inflammatory bowel disease.
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Affiliation(s)
- Hye-Myung Ryu
- Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea;
| | - S. M. Shamsul Islam
- Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea; (S.M.S.I.); (B.R.); (H.M.S.)
| | - Bushra Riaz
- Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea; (S.M.S.I.); (B.R.); (H.M.S.)
| | - Hasan M. Sayeed
- Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea; (S.M.S.I.); (B.R.); (H.M.S.)
| | - Bunsoon Choi
- Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, Republic of Korea;
| | - Seonghyang Sohn
- Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea;
- Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea; (S.M.S.I.); (B.R.); (H.M.S.)
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Yoon KN, Lee SJ, Keum GB, Song KY, Park JH, Song BS, Yu SY, Cho JH, Kim ES, Doo H, Kwak J, Kim S, Eun JB, Lee JH, Kim HB, Lee JH, Kim JK. Characteristics of Lactococcus petauri GB97 lysate isolated from porcine feces and its in vitro and in vivo effects on inflammation, intestinal barrier function, and gut microbiota composition in mice. Microbiol Spectr 2024; 12:e0133423. [PMID: 38019021 PMCID: PMC10782967 DOI: 10.1128/spectrum.01334-23] [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: 03/28/2023] [Accepted: 10/06/2023] [Indexed: 11/30/2023] Open
Abstract
IMPORTANCE Weaning is a crucial step in piglet management to improve pork production. During the weaning phase, disruption of epithelial barrier function and intestinal inflammation can lead to decreased absorption of nutrients and diarrhea. Therefore, maintaining a healthy intestine, epithelial barrier function, and gut microbiota composition in this crucial phase is strategic for optimal weaning in pigs. We isolated a lysate of Lactococcus petauri GB97 (LPL97) from healthy porcine feces and evaluated its anti-inflammatory activities, barrier integrity, and gut microbial changes in LPS-induced murine macrophages and DSS-induced colitis mice. We found that LPL97 regulated the immune response by downregulating the TLR4/NF-κB/MAPK signaling pathway both in vitro and in vivo. Furthermore, LPL97 alleviated the disruption of intestinal epithelial integrity and gut microbiota dysbiosis in colitis mice. This study indicates that LPL97 has the potential to be developed as an alternative feed additive to antibiotics for the swine industry.
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Affiliation(s)
- Ki-Nam Yoon
- Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, South Korea
- Department of Food Science and Technology, Graduate School of Chonnam National University, Gwangju, South Korea
| | - Soo-Jeong Lee
- Department of Food and Animal Biotechnology, Seoul National University, Seoul, South Korea
- Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea
- Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
- Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea
| | - Gi Beom Keum
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Ki-Young Song
- Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, South Korea
| | - Jong-Heum Park
- Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, South Korea
| | - Beom-Seok Song
- Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, South Korea
| | - Seung Yeob Yu
- Korean Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, South Korea
| | - Jae Hyoung Cho
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Eun Sol Kim
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Hyunok Doo
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Jinok Kwak
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Sheena Kim
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Jong-Bang Eun
- Department of Food Science and Technology, Graduate School of Chonnam National University, Gwangju, South Korea
| | - Ju Huck Lee
- Korean Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, South Korea
| | - Hyeun Bum Kim
- Department of Animal Resources Science, Dankook University, Cheonan, South Korea
| | - Ju-Hoon Lee
- Department of Food and Animal Biotechnology, Seoul National University, Seoul, South Korea
- Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea
- Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
- Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea
| | - Jae-Kyung Kim
- Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, South Korea
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Jin W, Ai H, Huang Q, Li C, He X, Jin Z, Zuo Y. Preclinical evidence of probiotics in ulcerative colitis: a systematic review and network meta-analysis. Front Pharmacol 2023; 14:1187911. [PMID: 37361217 PMCID: PMC10288114 DOI: 10.3389/fphar.2023.1187911] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
The imbalance of gastrointestinal microbial composition has been identified as the main factor of chronic inflammatory diseases. At present, probiotics have a beneficial effect on the microbial composition of the human gastrointestinal tract, but it is still controversial and the specific mechanism is unknown. The purpose of this network meta-analysis is to compare the mechanism of different probiotics on ulcerative colitis. PubMed, Embase, and Web of Science were searched till 16 November 2022. The SYRCLE risk bias assessment tool was used to assess the quality of the research studies. A total of 42 studies, 839 ulcerative colitis models, and 24 kinds of probiotics were finally included. The results showed that L. rhamnosus has the best effect in relieving weight loss and improving the Shannon index in the ulcerative colitis model. E. faecium has the best effect in reducing colon injury; L. reuteri has the best effect in reducing the DAI; L. acidophilus has the best effect in reducing the HIS index and increasing the expression of tight junction protein ZO-1; and L. coryniformis has the best effect in reducing the content of serum pro-inflammatory factor TNF-α. It indicated that probiotics can improve ulcerative colitis by improving histopathological manifestations, reducing inflammatory reaction, and repairing the mucosal barrier, and different probiotics showed different effects. However, considering the limitations of this study, preclinical studies that require more large samples and high-quality and more reliable and rigorous experimental designs and reports need to be conducted in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#record details, identifier CRD42022383383.
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Affiliation(s)
- Wenqin Jin
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huangping Ai
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qingqing Huang
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuncai Li
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiang He
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhao Jin
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuling Zuo
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Hasan N, Yang H. Evaluation of microbial and vancomycin treatments in ulcerative colitis in murine models. PLoS One 2023; 18:e0285613. [PMID: 37167242 PMCID: PMC10174502 DOI: 10.1371/journal.pone.0285613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 04/26/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. METHODS Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. RESULTS After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. CONCLUSION Our results concluded that treatment duration and preparation methods affect the microbial therapies' efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.
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Affiliation(s)
- Nihal Hasan
- Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, People’s Republic of China
- Faculty of Health Science, Al-Baath University, Homs, Syria
| | - Hongyi Yang
- Department of Microbiology, Northeast Forestry University, Harbin, Heilongjiang, People’s Republic of China
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Huang Z, Gong L, Jin Y, Stanton C, Ross RP, Zhao J, Yang B, Chen W. Different Effects of Different Lactobacillus acidophilus Strains on DSS-Induced Colitis. Int J Mol Sci 2022; 23:ijms232314841. [PMID: 36499169 PMCID: PMC9738729 DOI: 10.3390/ijms232314841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 12/05/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a worldwide chronic intestinal inflammatory immune-related disease. In this study, mice with dextran sulfate sodium (DSS)-induced colitis were used to evaluate the effect of Lactobacillus acidophilus on colitis. The results revealed that L. acidophilus CCFM137 and FAHWH11L56 show potential for relieving colitis symptoms, while L. acidophilus FGSYC48L79 did not show a protective effect. Moreover, L. acidophilus NCFM and FAHWH11L56 showed similar effects on various indicators of DSS-induced colitis, increasing the IL-10 and IL-17 in the colon, and modifying the CCL2/CCR2 axis and CCL3/CCR1 axis. For L. acidophilus CCFM137, its effects on colitis were different from the above two strains. Moreover, L. acidophilus FGSYC48L79 had negative effects on colitis by increasing the abundance of harmful bacteria in the gut microbiota and may promote the signaling of chemokines and their receptors. This may be related to its special genome compared to the other strains.
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Affiliation(s)
- Zheng Huang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Lei Gong
- Department of Gastroenterology, The Affiliated Wuxi Second People’s Hospital of Nanjing Medical University, Wuxi 214122, China
- Correspondence: (L.G.); (B.Y.); Tel.: +86-510-8591-2155 (B.Y.)
| | - Yan Jin
- Department of Gastroenterology, The Affiliated Wuxi Second People’s Hospital of Nanjing Medical University, Wuxi 214122, China
| | - Catherine Stanton
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi 214122, China
- APC Microbiome Ireland, University College Cork, T12 K8AF Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996 Co. Cork, Ireland
| | - Reynolds Paul Ross
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi 214122, China
- APC Microbiome Ireland, University College Cork, T12 K8AF Cork, Ireland
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi 214122, China
- Correspondence: (L.G.); (B.Y.); Tel.: +86-510-8591-2155 (B.Y.)
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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Song S, Jeong A, Lim J, Kim B, Park D, Oh S. Lactiplantibacillus plantarum
L67
probiotics vs paraprobiotics for reducing pro‐inflammatory responses in colitis mice. INT J DAIRY TECHNOL 2022. [DOI: 10.1111/1471-0307.12918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Sooyeon Song
- Department of Animal Science Jeonbuk National University 587 Baekje‐Daero, Deojin‐Gu Jeonju‐Si Jellabuk‐Do 54896 South Korea
- Agricultural Convergence Technology Jeonbuk National University 587 Baekje‐Daero, Deojin‐Gu Jeonju‐Si Jellabuk‐Do 54896 South Korea
| | - Anna Jeong
- Division of Animal Science Chonnam National University 77 Yongbong‐Ro, Buk‐Gu Gwang‐Ju 61186 South Korea
| | - Jina Lim
- Division of Animal Science Chonnam National University 77 Yongbong‐Ro, Buk‐Gu Gwang‐Ju 61186 South Korea
- Department of Animal Biotechnology and Environment Animal Genomics and Bioinformatics National Institute of Animal Science 1500 Kongjwipatjwi‐ro Jellabuk‐do 55365 South Korea
| | - Bum‐Keun Kim
- Korea Food Research Institute 245, Nongsaengmyeong‐ro Jeollabuk‐do 55365 South Korea
| | - Dong‐June Park
- Korea Food Research Institute 245, Nongsaengmyeong‐ro Jeollabuk‐do 55365 South Korea
| | - Sejong Oh
- Division of Animal Science Chonnam National University 77 Yongbong‐Ro, Buk‐Gu Gwang‐Ju 61186 South Korea
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Liu Y, Xiao W, Yu L, Tian F, Wang G, Lu W, Narbad A, Chen W, Zhai Q. Evidence from comparative genomic analyses indicating that Lactobacillus-mediated irritable bowel syndrome alleviation is mediated by conjugated linoleic acid synthesis. Food Funct 2021; 12:1121-1134. [PMID: 33427835 DOI: 10.1039/d0fo02616f] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic intestinal disorder accompanied by low-grade inflammation, visceral hypersensitivity, and gut microbiota dysbiosis. Several studies have indicated that Lactobacillus supplementation can help to alleviate IBS symptoms and that these effects are strain-specific. Therefore, this study aimed to investigate the key physiological characteristics and functional genes contributing to the IBS-alleviating effects of Lactobacillus. An IBS model was established by subjecting C57BL/6 mice to Citrobacter rodentium ingestion and water avoidance stress. Lactobacillus strains with different physiological characteristics were administered to mice intragastrically for 4 weeks (5 × 109 CFU/0.2 mL per mouse per day). Indicators of colonic inflammation, visceral hypersensitivity, and gut microbiota were also evaluated. Finally, differences in functional genes between Lactobacillus strains were analyzed by a comparative genomic analysis, and the relationships between the physiological characteristics, functional genes, and IBS-alleviating effects of the strains were quantified using correlation analysis. Among the eight tested Lactobacillus strains, only Lactobacillus plantarum CCFM8610 significantly inhibited the expression of IL-1β, IL-6, PAR-2, and mast cell tryptase. L. plantarum CCFM8610 also significantly increased the intestinal barrier function, inhibited visceral hypersensitivity symptoms, and modulated the gut microbiota diversity and composition. The correlation analysis of factors associated with the IBS-alleviating effects of Lactobacillus revealed the ability to synthesize conjugated linoleic acid as the most strongly associated physiological characteristic and COG1028-related genes as the most strongly associated functional genes. In conclusion, these findings can facilitate the rapid screening of Lactobacillus strains with IBS-alleviating effects and lay a foundation for studies of the related mechanisms.
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Affiliation(s)
- Yang Liu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Wei Xiao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, Jiangsu 214122, China and (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China and (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Arjan Narbad
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, Jiangsu 214122, China and Gut Health and Food Safety Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China and Beijing Innovation Center of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. and International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, Jiangsu 214122, China
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Ding S, Yan W, Fang J, Jiang H, Liu G. Potential role of Lactobacillus plantarum in colitis induced by dextran sulfate sodium through altering gut microbiota and host metabolism in murine model. SCIENCE CHINA-LIFE SCIENCES 2021; 64:1906-1916. [DOI: 10.1007/s11427-020-1835-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023]
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10
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Protective Effect of Prunus mume Fermented with Mixed Lactic Acid Bacteria in Dextran Sodium Sulfate-Induced Colitis. Foods 2020; 10:foods10010058. [PMID: 33383792 PMCID: PMC7823353 DOI: 10.3390/foods10010058] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/18/2020] [Accepted: 12/26/2020] [Indexed: 02/07/2023] Open
Abstract
The fruit of Prunus mume (PM) is widely cultivated in East Asia, and it has been used as a folk medication for gastrointestinal disorders, e.g., diarrhea, stomach ache and ulceration. In this study, the pectinase-treated PM juice (PJ) was fermented with Lactobacillus strains containing fundamental organic acids and free amino acids. The PJ fermented with Lactobacillus plantarum and L. casei (FP) was investigated for its protective effect in dextran sodium sulfate (DSS)-induced colitis mice model. The administration of FP reduced lipid peroxidation and histopathological colitis symptoms, e.g., shortening of the colon length, depletion of mucin, epithelial injury and ulceration, in colonic tissues. The FP-supplemented group showed the alleviation of pro-inflammatory cytokines. Compared with the DSS control group, the supplementation of FP significantly reduced the levels of serum interferon-γ (IFN-γ), interleukin (IL)-1β, IL-6, IL-12 and IL-17 as well as colonic tumor necrosis factor-α, IFN-γ, IL-12 and IL-17. Furthermore, the DSS-induced TUNEL-positive area was significantly reduced by the FP supplementation. These results show that the supplementation of FP fermented with mixed lactic acid bacteria, L. plantarum and L. casei, elucidated the protective effect in DSS-induced colitis mice. Hence, this study suggests that FP can be utilized as a natural therapeutic agent for colitis and intestinal inflammation.
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Kang M, Choe D, Kim K, Cho BK, Cho S. Synthetic Biology Approaches in The Development of Engineered Therapeutic Microbes. Int J Mol Sci 2020; 21:ijms21228744. [PMID: 33228099 PMCID: PMC7699352 DOI: 10.3390/ijms21228744] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/11/2020] [Accepted: 11/17/2020] [Indexed: 12/24/2022] Open
Abstract
Since the intimate relationship between microbes and human health has been uncovered, microbes have been in the spotlight as therapeutic targets for several diseases. Microbes contribute to a wide range of diseases, such as gastrointestinal disorders, diabetes and cancer. However, as host-microbiome interactions have not been fully elucidated, treatments such as probiotic administration and fecal transplantations that are used to modulate the microbial community often cause nonspecific results with serious safety concerns. As an alternative, synthetic biology can be used to rewire microbial networks such that the microbes can function as therapeutic agents. Genetic sensors can be transformed to detect biomarkers associated with disease occurrence and progression. Moreover, microbes can be reprogrammed to produce various therapeutic molecules from the host and bacterial proteins, such as cytokines, enzymes and signaling molecules, in response to a disturbed physiological state of the host. These therapeutic treatment systems are composed of several genetic parts, either identified in bacterial endogenous regulation systems or developed through synthetic design. Such genetic components are connected to form complex genetic logic circuits for sophisticated therapy. In this review, we discussed the synthetic biology strategies that can be used to construct engineered therapeutic microbes for improved microbiome-based treatment.
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Affiliation(s)
- Minjeong Kang
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; (M.K.); (D.C.); (K.K.)
| | - Donghui Choe
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; (M.K.); (D.C.); (K.K.)
| | - Kangsan Kim
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; (M.K.); (D.C.); (K.K.)
| | - Byung-Kwan Cho
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; (M.K.); (D.C.); (K.K.)
- Innovative Biomaterials Research Center, KI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
- Intelligent Synthetic Biology Center, Daejeon 34141, Korea
- Correspondence: (B.-K.C.); (S.C.)
| | - Suhyung Cho
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; (M.K.); (D.C.); (K.K.)
- Innovative Biomaterials Research Center, KI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
- Correspondence: (B.-K.C.); (S.C.)
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12
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Heumann A, Assifaoui A, Da Silva Barreira D, Thomas C, Briandet R, Laurent J, Beney L, Lapaquette P, Guzzo J, Rieu A. Intestinal release of biofilm-like microcolonies encased in calcium-pectinate beads increases probiotic properties of Lacticaseibacillus paracasei. NPJ Biofilms Microbiomes 2020; 6:44. [PMID: 33116127 PMCID: PMC7595111 DOI: 10.1038/s41522-020-00159-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 10/06/2020] [Indexed: 12/15/2022] Open
Abstract
In this study, we show that calcium pectinate beads (CPB) allow the formation of 20 µm spherical microcolonies of the probiotic bacteria Lacticaseibacillus paracasei (formerly designated as Lactobacillus paracasei) ATCC334 with a high cell density, reaching more than 10 log (CFU/g). The bacteria within these microcolonies are well structured and adhere to a three-dimensional network made of calcium-pectinate through the synthesis of extracellular polymeric substances (EPS) and thus display a biofilm-like phenotype, an attractive property for their use as probiotics. During bacterial development in the CPB, a coalescence phenomenon arises between neighboring microcolonies accompanied by their peripheral spatialization within the bead. Moreover, the cells of L. paracasei ATCC334 encased in these pectinate beads exhibit increased resistance to acidic stress (pH 1.5), osmotic stress (4.5 M NaCl), the freeze-drying process and combined stresses, simulating the harsh conditions encountered in the gastrointestinal (GI) tract. In vivo, the oral administration of CPB-formulated L. paracasei ATCC334 in mice demonstrated that biofilm-like microcolonies are successfully released from the CPB matrix in the colonic environment. In addition, these CPB-formulated probiotic bacteria display the ability to reduce the severity of a DSS-induced colitis mouse model, with a decrease in colonic mucosal injuries, less inflammation, and reduced weight loss compared to DSS control mice. To conclude, this work paves the way for a new form of probiotic administration in the form of biofilm-like microcolonies with enhanced functionalities.
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Affiliation(s)
- Arnaud Heumann
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France
| | - Ali Assifaoui
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France.
| | - David Da Silva Barreira
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France
| | - Charles Thomas
- Université de Bourgogne Franche-Comté (UBFC), LNC UMR 1231, F-21000 Dijon, France; INSERM, LNC UMR 1231, F-21000, Dijon, France
- Université de Bourgogne Franche-Comté (UBFC), LipSTIC LabEx, F-21000, Dijon, France
| | - Romain Briandet
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France
| | - Julie Laurent
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France
| | - Laurent Beney
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France
| | - Pierre Lapaquette
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France
| | - Jean Guzzo
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France
| | - Aurélie Rieu
- Université de Bourgogne Franche-Comté (UBFC), AgroSup Dijon, UMR PAM A 02.102, F-21000, Dijon, France.
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13
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Sato N, Garcia-Castillo V, Yuzawa M, Islam MA, Albarracin L, Tomokiyo M, Ikeda-Ohtsubo W, Garcia-Cancino A, Takahashi H, Villena J, Kitazawa H. Immunobiotic Lactobacillus jensenii TL2937 Alleviates Dextran Sodium Sulfate-Induced Colitis by Differentially Modulating the Transcriptomic Response of Intestinal Epithelial Cells. Front Immunol 2020; 11:2174. [PMID: 33042131 PMCID: PMC7527445 DOI: 10.3389/fimmu.2020.02174] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 08/10/2020] [Indexed: 12/11/2022] Open
Abstract
Immunobiotics have emerged as a promising intervention to alleviate intestinal damage in inflammatory bowel disease (IBD). However, the beneficial properties of immunobiotics are strain dependent and, therefore, each strain has to be evaluated in order to demonstrate its potential application in IBD. Our previous in vitro and in vivo studies demonstrated that Lactobacillus jensenii TL2937 attenuates gut acute inflammatory response triggered by Toll-like receptor 4 activation. However, its effect on colitis has not been evaluated before. In this work, we studied whether the TL2937 strain was able to protect against the development of colitis in a dextran sodium sulfate (DSS)-induced mouse model and we delved into the mechanisms of action by evaluating the effect of the immunobiotic bacteria on the transcriptomic response of DSS-challenged intestinal epithelial cells. L. jensenii TL2937 was administered to adult BALB/c mice before the induction of colitis by the administration of DSS. Colitis and the associated inflammatory response were evaluated for 14 days. Mice fed with L. jensenii TL2937 had lower disease activity index and alterations of colon length when compared to control mice. Reduced myeloperoxidase activity, lower production of pro-inflammatory (TNF-α, IL-1, CXCL1, MCP-1, IL-15, and IL-17), and higher levels of immunoregulatory (IL-10 and IL-27) cytokines were found in the colon of TL2937-treated mice. In addition, the treatment of porcine intestinal epithelial (PIE) cells with L. jensenii TL2937 before the challenge with DSS differentially regulated the activation of the JNK pathway, leading to an increase in epithelial cell integrity and to a differential immunotranscriptomic response. TL2937-treated PIE cells had a significant reduction in the expression of inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6, IL-15), chemokines (CCL2, CCL4, CCL8, CXCL4, CXCL5, CXCL9, CXCL10), adhesion molecules (SELE, SELL, EPCAM), and other immune factors (NCF1, NCF2, NOS2, SAA2) when compared to control cells after the challenge with DSS. The findings of this work indicate that (a) L. jensenii TL2937 is able to alleviate DSS-induced colitis suggesting a potential novel application for this immunobiotic strain, (b) the modulation of the transcriptomic response of intestinal epithelial cells would play a key role in the beneficial effects of the TL2937 strain on colitis, and (c) the in vitro PIE cell immunoassay system could be of value for the screening and selection of new immunobiotic strains for their application in IBD.
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Affiliation(s)
- Nana Sato
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Valeria Garcia-Castillo
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile
| | - Mao Yuzawa
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Md. Aminul Islam
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Department of Medicine, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Leonardo Albarracin
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Laboratory of Immunobiotechnology, Reference Center for Lactobacilli (CERELA-National Council for Scientific and Technological Research), San Miguel de Tucumán, Argentina
- Laboratory of Computing Science, Faculty of Exact Sciences and Technology, Tucuman University, San Miguel de Tucumán, Argentina
| | - Mikado Tomokiyo
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Wakako Ikeda-Ohtsubo
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Apolinaria Garcia-Cancino
- Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile
| | - Hideki Takahashi
- Laboratory of Plant Pathology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Plant Immunology Unit, International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Julio Villena
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Department of Medicine, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
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Jin J, Wu S, Xie Y, Liu H, Gao X, Zhang H. Live and heat-killed cells of Lactobacillus plantarum Zhang-LL ease symptoms of chronic ulcerative colitis induced by dextran sulfate sodium in rats. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.103994] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
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15
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Hasannejad-Bibalan M, Mojtahedi A, Eshaghi M, Rohani M, Pourshafie MR, Talebi M. The effect of selected Lactobacillus strains on dextran sulfate sodium-induced mouse colitis model. Acta Microbiol Immunol Hung 2020; 67:138-142. [PMID: 32554841 DOI: 10.1556/030.2020.00834] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 05/28/2019] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) comprises two major illnesses: Crohn's disease (CD) and ulcerative colitis (UC). Dextran sulfate sodium (DSS) mouse colitis model has been used in understanding the mechanism of IBD. This study was conducted to examine selected Lactobacillus spp. as potential IBD treatment in the DSS-induced animal model. Balb/c mice were used and colitis was induced by adding 5% dextran sodium sulfate into the drinking water for 8 days. Colon length, disease activity index (DAI) and histological analysis were measured as markers of inflammation in DSS colitis mice. The majority of the Lactobacillus species significantly prevented the shortening of the colon length compared with the DSS group. The DAI scores of mice were significantly reduced following usage of four Lactobacillus strains included: Lactobacillus plantarum 03 and 06, Lactobacillus brevis 02 and Lactobacillus rhamnosus 01. The histological analysis exhibited that oral administration of Lactobacillus strains had therapeutic effects on mice colitis. L. plantarum and L. brevis showed better therapeutic effect against DSS-induced acute colitis mice. The probiotic activities of these three isolates indicated that the probiotic effects were strain specific and none of these useful bacteria could exhibit all of the valued probiotic properties simultaneously.
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Affiliation(s)
| | - Ali Mojtahedi
- 1Department of Microbiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Morteza Eshaghi
- 2Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Rohani
- 3Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | | | - Malihe Talebi
- 2Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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16
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Komaki S, Haque A, Miyazaki H, Matsumoto T, Nakamura S. Unexpected effect of probiotics by Lactococcus lactis subsp. lactis against colitis induced by dextran sulfate sodium in mice. J Infect Chemother 2020; 26:549-553. [PMID: 32122783 DOI: 10.1016/j.jiac.2020.01.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 01/15/2020] [Accepted: 01/22/2020] [Indexed: 02/08/2023]
Abstract
Ulcerative colitis (UC) is a representative intestinal chronic inflammatory disease whose incidence is rapidly increasing worldwide. It was previously shown that some specific probiotics help to guard against UC. In this study, we analyzed the effect of Lactococcus lactis subsp. lactis JCM5805 (L. lactis), which has been put to practical use as a probiotic, on the pathogenesis of UC using a dextran sulfate sodium-induced colitis mouse model. Survival rate, length, and histopathological parameters of the colon were elucidated. Further, the concentrations of inflammatory cytokines in serum were measured. As a result, the oral administration of high-dose L. lactis showed significant decreases in survival rate and colon length. Histopathological analysis showed that a bleeding appearance was observed in the L. lactis group, and the histology scores in the L. lactis group were significantly higher than those in the normal saline group. Furthermore, the levels of interferon gamma, tumor necrosis factor alpha, and interleukin-6 were significantly elevated in the L. lactis group. These results support that high-dose administration of L. lactis deteriorates intestinal inflammation and suggest that the careful selection of probiotics strains and administration dose is important for improving colitis including UC.
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Affiliation(s)
- Shinichirou Komaki
- Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
| | - Anwarul Haque
- International University of Health and Welfare, School of Medicine, Kozunomori 4-3, Narita City, Chiba, 286-8686, Japan
| | - Haruko Miyazaki
- Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan
| | - Tetsuya Matsumoto
- International University of Health and Welfare, School of Medicine, Kozunomori 4-3, Narita City, Chiba, 286-8686, Japan
| | - Shigeki Nakamura
- Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan
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17
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Grosu IA, Pistol GC, Marin DE, Cişmileanu A, Palade LM, Ţăranu I. Effects of Dietary Grape Seed Meal Bioactive Compounds on the Colonic Microbiota of Weaned Piglets With Dextran Sodium Sulfate-Induced Colitis Used as an Inflammatory Model. Front Vet Sci 2020; 7:31. [PMID: 32161762 PMCID: PMC7054226 DOI: 10.3389/fvets.2020.00031] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 01/14/2020] [Indexed: 12/18/2022] Open
Abstract
Microbiota affects host health and plays an important role in dysbiosis. The study examined the effect of diet including grape seed meal (GSM) with its mixture of bioactive compounds on the large intestine microbiota and short-chain fatty acid synthesis in weaned piglets treated with dextran sodium sulfate (DSS) as a model for inflammatory bowel diseases. Twenty-two piglets were included in four experimental groups based on their diet: control, DSS (1 g/kg/b.w.+control diet), GSM (8% grape seed meal inclusion in control diet), and DSS+GSM (1 g/kg/b.w., 8% grape seed meal in control diet). After 30 days, the colon content was isolated and used for microbiota sequencing on an Illumina MiSeq platform. QIIME 1.9.1 pipeline was used to process the raw sequences. Both GSM and DSS alone and in combination affected the diversity indices and Firmicutes:Bacteroidetes ratio, with significantly higher values in the DSS-afflicted piglets for Proteobacteria phylum, Roseburia, Megasphera and CF231 genus, and lower values for Lactobacillus. GSM with high-fiber, polyphenol and polyunsaturated fatty acid (PUFA) content increased the production of butyrate and isobutyrate, stimulated the growth of beneficial genera like Prevotella and Megasphaera, while countering the relative abundance of Roseburia, reducing it to half of the DSS value and contributing to the management of the DSS effects.
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Affiliation(s)
- Iulian A Grosu
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
| | - Gina C Pistol
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
| | - Daniela E Marin
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
| | - Ana Cişmileanu
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
| | - Laurenţiu M Palade
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
| | - Ionelia Ţăranu
- Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
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18
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George NS, Cheung L, Luthria DL, Santin M, Dawson HD, Bhagwat AA, Smith AD. Pomegranate peel extract alters the microbiome in mice and dysbiosis caused by Citrobacter rodentium infection. Food Sci Nutr 2019; 7:2565-2576. [PMID: 31428344 PMCID: PMC6694437 DOI: 10.1002/fsn3.1106] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 05/08/2019] [Indexed: 12/28/2022] Open
Abstract
Treatment of mice with a pomegranate peel extract (PPX) decreased the pathogenicity of Citrobacter rodentium (Cr) infections. Here, we investigate the effects of PPX on the microbiome of uninfected or Cr-infected C3H/HeNCr mice by 16S rRNA gene sequencing. Mice were treated with water or PPX for 14 days, feces were collected, and then, the mice were infected with Cr and feces collected again at day 6 postinfection. DNA was isolated from the fecal samples and subjected to 16S rRNA gene sequencing to determine the microbial composition. Differences in the composition of the microbiome were observed for untreated and PPX-treated mice with PPX mice having decreased diversity. PPX treatment decreased the Firmicutes/Bacteroidetes ratio by increasing Bacteroidetes and decreasing Firmicutes levels. The decrease in Firmicutes was driven by a large reduction in Lactobacillus. PPX treatment increased the abundance of Proteobacteria and Verrucomicrobiae and decreased Actinobacteria. The relative abundance of Cr reached 22% in water-treated but only 5% in PPX-treated infected mice. These results suggest that consumption of pomegranate polyphenols altered the microbiome, making it more resistant to displacement by infection with Cr, indicating that pomegranate polyphenols may mitigate the pathogenic effects of food-borne bacterial pathogens.
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Affiliation(s)
- Nadja S. George
- Environmental Microbial and Food Safety LabBeltsville Agricultural Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
| | - Lumei Cheung
- Diet Genomics and Immunology LabBeltsville Human Nutrition Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
| | - Devanand L. Luthria
- Composition Methods Development LabBeltsville Human Nutrition Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
| | - Monica Santin
- Environmental Microbial and Food Safety LabBeltsville Agricultural Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
| | - Harry D. Dawson
- Diet Genomics and Immunology LabBeltsville Human Nutrition Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
| | - Arvind A. Bhagwat
- Environmental Microbial and Food Safety LabBeltsville Agricultural Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
- Present address:
Central Chinmaya Mission TrustPowaiMumbaiIndia
| | - Allen D. Smith
- Diet Genomics and Immunology LabBeltsville Human Nutrition Research CenterAgricultural Research Service, Department of AgricultureBeltsvilleMaryland
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19
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WANG H, LI S, LI H, DU F, GUAN J, WU Y. Mechanism of Probiotic VSL#3 Inhibiting NF-κB and TNF-α on Colitis through TLR4-NF-κB Signal Pathway. IRANIAN JOURNAL OF PUBLIC HEALTH 2019; 48:1292-1300. [PMID: 31497551 PMCID: PMC6708536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND We aimed to investigate the effect of probiotic VSL#3 on NF-κB and TNF-α in rats with colitis and the correlation with TLR4-NF-κB signal pathway. METHODS Sixty Sprague Dawley (SD) rats were divided into the control, model and therapy groups (n=20) according to the random number table. Rats in the model and therapy groups were modeled for colitis, and rats in the therapy group were intragastrically administered with probiotic VSL#3. The expression of TLR4 and NF-κB protein, and the levels of NF-κB, TLR4, and TNF-α mRNA in the colon tissue were detected. The concentration of TNF-α in the serum after modeling but before intragastric administration (T0), 3d (T1) and 7d after intragastric administration (T2) was detected. RESULTS The expression of TLR4 and NF-κB p65 protein, and the levels of TLR4, NF-κB, and TNF-α mRAN in the therapy group decreased (P < 0.001). At T0, T1, and T2, the concentration of TNF-α in the model and control groups increased (P < 0.001). TLR4 and NF-κB in the therapy group were positively correlated with TNF-α mRAN (P < 0.050).Conclusion: In conclusion, probiotic VSL#3 inhibits the expression of NF-κB and TNF-α in rats with colitis through TLR4-NF-κB signal pathway, so it is expected to be a first choice drug for the treatment of colitis. CONCLUSION In conclusion, probiotic VSL#3 inhibits the expression of NF-κB and TNF-α in rats with colitis through TLR4-NF-κB signal pathway, so it is expected to be a first choice drug for the treatment of colitis.
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Affiliation(s)
- Hui WANG
- Department of Immunology, Qiqihar Medical University, Qiqihar 161000, P.R. China,Corresponding Author:
| | - Shuhua LI
- Department of Traditional Chinese Medicine, The First Hospital of Qiqihar, Qiqihar 161000, P.R. China
| | - Houzhong LI
- Department of Pharmacology, Mudanjiang Medical University, Mudanjiang 157011, P.R. China
| | - Fengxia DU
- Department of Pathogen Biology, Qiqihar Medical University, Qiqihar 161000, P.R. China
| | - Jie GUAN
- Department of Immunology, Qiqihar Medical University, Qiqihar 161000, P.R. China
| | - Yanmin WU
- Department of Immunology, Qiqihar Medical University, Qiqihar 161000, P.R. China
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21
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Wang G, Liu Y, Lu Z, Yang Y, Xia Y, Lai PFH, Ai L. The ameliorative effect of a Lactobacillus strain with good adhesion ability against dextran sulfate sodium-induced murine colitis. Food Funct 2019; 10:397-409. [DOI: 10.1039/c8fo01453a] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The objective of this study was to effectively screen out a Lactobacillus strain with excellent adhesion ability and ameliorative effect on the disease symptoms of a murine ulcerative colitis model.
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Affiliation(s)
- Guangqiang Wang
- Shanghai Engineering Research Center of Food Microbiology
- School of Medical Instrument and Food Engineering
- University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Yingnan Liu
- Shanghai Engineering Research Center of Food Microbiology
- School of Medical Instrument and Food Engineering
- University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Zhi Lu
- Infinitus (China) Company Ltd
- Guangzhou 510623
- China
| | - Yiting Yang
- Infinitus (China) Company Ltd
- Guangzhou 510623
- China
| | - Yongjun Xia
- Shanghai Engineering Research Center of Food Microbiology
- School of Medical Instrument and Food Engineering
- University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Phoency F.-H. Lai
- Shanghai Engineering Research Center of Food Microbiology
- School of Medical Instrument and Food Engineering
- University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Lianzhong Ai
- Shanghai Engineering Research Center of Food Microbiology
- School of Medical Instrument and Food Engineering
- University of Shanghai for Science and Technology
- Shanghai 200093
- China
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Martín R, Chain F, Miquel S, Motta JP, Vergnolle N, Sokol H, Langella P. Using murine colitis models to analyze probiotics-host interactions. FEMS Microbiol Rev 2018; 41:S49-S70. [PMID: 28830096 DOI: 10.1093/femsre/fux035] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 06/08/2017] [Indexed: 02/07/2023] Open
Abstract
Probiotics are defined as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. So, to consider a microorganism as a probiotic, a demonstrable beneficial effect on the health host should be shown as well as an adequate defined safety status and the capacity to survive transit through the gastrointestinal tract and to storage conditions. In this review, we present an overview of the murine colitis models currently employed to test the beneficial effect of the probiotic strains as well as an overview of the probiotics already tested. Our aim is to highlight both the importance of the adequate selection of the animal model to test the potential probiotic strains and of the value of the knowledge generated by these in vivo tests.
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Affiliation(s)
- Rebeca Martín
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Florian Chain
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Sylvie Miquel
- Laboratoire Microorganismes: Génome et Environnement (LMGE), UMR CNRS 6023, Université Clermont-Auvergne, 63000 Clermont-Ferrand, France
| | - Jean-Paul Motta
- Department of Biological Science, Inflammation Research Network, University of Calgary, AB T3E 4N1, Canada.,IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, F-31300 Toulouse, France
| | - Nathalie Vergnolle
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, F-31300 Toulouse, France
| | - Harry Sokol
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.,Sorbonne University - Université Pierre et Marie Curie (UPMC), 75252 Paris, France.,Institut National de la Santé et de la Recherche Médicale (INSERM) Equipe de Recherche Labélisée (ERL) 1157, Avenir Team Gut Microbiota and Immunity, 75012 Paris, France.,Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique - Hopitaux de Paris, UPMC, 75012 Paris, France
| | - Philippe Langella
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
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23
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de Silva PS, Hansen HH, Wehberg S, Friedman S, Nørgård BM. Risk of Ectopic Pregnancy in Women With Inflammatory Bowel Disease: A 22-Year Nationwide Cohort Study. Clin Gastroenterol Hepatol 2018; 16:83-89.e1. [PMID: 28694133 DOI: 10.1016/j.cgh.2017.06.054] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 06/12/2017] [Accepted: 06/27/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Few data are available on adverse events of pregnancy in women with inflammatory bowel diseases (IBD), such as ectopic pregnancy. We assessed the risk of ectopic pregnancy in pregnancies of women in Denmark with IBD compared with those without IBD over a 22-year period. We also examined the disease-specific risks of ectopic pregnancies in pregnancies of women with ulcerative colitis (UC) or Crohn's disease (CD) who underwent IBD-related surgical procedures. METHODS We performed a retrospective study of all women of child-bearing age (ages, 15-50 y) registered in the Danish National Patient Registry with at least 1 pregnancy during the period from January 1994 through December 31, 2015. We collected data on all women with an ectopic pregnancy, hydatidiform mole, miscarriages (spontaneous and other abortions, including abnormal pregnancy products, missed abortion, and pregnancy without a fetus), induced abortions, and births in women with and without IBD. Our study population included 7548 pregnancies in women with UC, 6731 pregnancies in women with CD, and 1,832,732 pregnancies in women without IBD. We controlled for multiple covariates, including pelvic and abdominal surgery. RESULTS Women with CD had a greater risk of ectopic pregnancy, per pregnancy, than women without IBD (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.01-1.49), whereas women with UC did not (OR, 0.98; 95% CI, 0.80-1.20). In pregnancies of women with CD and UC who underwent IBD-related surgery before pregnancy, there was a nonsignificant increase in risk of ectopic pregnancy compared with pregnancies in women with IBD who did not have surgery (OR, 1.49; 95% CI, 0.91-2.44 for CD, and OR, 1.17; 95% CI, 0.54-2.52 for UC). CONCLUSIONS We found a statistically significant increased risk of ectopic pregnancy in pregnancies of women with CD compared with pregnancies of women without IBD. Surgery for IBD before pregnancy increased the risk of ectopic pregnancy, although this increase was not statistically significant.
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Affiliation(s)
- Punyanganie S de Silva
- Center for Crohn's and Colitis, Division of Gastroenterology, Hepatology & Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Helene H Hansen
- Center for Clinical Epidemiology, Odense University Hospital, Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark
| | - Sonja Wehberg
- Center for Clinical Epidemiology, Odense University Hospital, Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Crohn's and Colitis, Division of Gastroenterology, Hepatology & Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Center for Clinical Epidemiology, Odense University Hospital, Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark
| | - Bente M Nørgård
- Center for Crohn's and Colitis, Division of Gastroenterology, Hepatology & Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Center for Clinical Epidemiology, Odense University Hospital, Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark
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24
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Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mähler A, Balogh A, Markó L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Frätzer C, Krannich A, Gollasch M, Grohme DA, Côrte-Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Müller DN. Salt-responsive gut commensal modulates T H17 axis and disease. Nature 2017; 551:585-589. [PMID: 29143823 PMCID: PMC6070150 DOI: 10.1038/nature24628] [Citation(s) in RCA: 903] [Impact Index Per Article: 112.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 10/10/2017] [Indexed: 12/12/2022]
Abstract
A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH17) cells, which can also contribute to hypertension. Induction of TH17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased TH17 cells and increased blood pressure. Our results connect high salt intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.
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Affiliation(s)
- Nicola Wilck
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Mariana G Matus
- Center for Microbiome Informatics and Therapeutics, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Sean M Kearney
- Center for Microbiome Informatics and Therapeutics, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Scott W Olesen
- Center for Microbiome Informatics and Therapeutics, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Kristoffer Forslund
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Hendrik Bartolomaeus
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
| | - Stefanie Haase
- Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany
| | - Anja Mähler
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - András Balogh
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Lajos Markó
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Olga Vvedenskaya
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- Integrative Proteomics and Metabolomics Platform, Berlin Institute for Medical Systems Biology BIMSB, 13125 Berlin, Germany
- Berlin School of Integrative Oncology, Charité University Medicine Berlin, Berlin, Germany
| | - Friedrich H Kleiner
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
| | - Dmitry Tsvetkov
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
| | - Lars Klug
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Paul I Costea
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Shinichi Sunagawa
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
- Institute of Microbiology, ETH Zurich, 8092 Zurich, Switzerland
| | - Lisa Maier
- European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany
| | - Natalia Rakova
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany
| | - Valentin Schatz
- Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany
| | - Patrick Neubert
- Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany
| | | | | | - Maik Gollasch
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
| | - Diana A Grohme
- Translational Immunology, Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, Technical University of Dresden, 01307 Dresden, Germany
| | - Beatriz F Côrte-Real
- VIB Laboratory of Translational Immunomodulation, VIB Center for Inflammation Research (IRC), Hasselt University, Campus Diepenbeek, 3590 Diepenbeek, Belgium
| | - Roman G Gerlach
- Project Group 5, Robert Koch Institute, 38855 Wernigerode, Germany
| | - Marijana Basic
- Hannover Medical School, Institute for Laboratory Animal Science and Central Animal Facility, 30625 Hannover, Germany
| | - Athanasios Typas
- European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany
| | - Chuan Wu
- Experimental Immunology Branch, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
| | - Jens M Titze
- Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Jonathan Jantsch
- Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany
| | - Michael Boschmann
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Ralf Dechend
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Markus Kleinewietfeld
- Translational Immunology, Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, Technical University of Dresden, 01307 Dresden, Germany
- VIB Laboratory of Translational Immunomodulation, VIB Center for Inflammation Research (IRC), Hasselt University, Campus Diepenbeek, 3590 Diepenbeek, Belgium
- Center for Regenerative Therapies Dresden (CRTD), 01307 Dresden, Germany
| | - Stefan Kempa
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
- Integrative Proteomics and Metabolomics Platform, Berlin Institute for Medical Systems Biology BIMSB, 13125 Berlin, Germany
| | - Peer Bork
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
- Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany
- Department of Bioinformatics, Biocenter, University of Würzburg, 97074 Würzburg, Germany
| | - Ralf A Linker
- Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany
| | - Eric J Alm
- Center for Microbiome Informatics and Therapeutics, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Dominik N Müller
- Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
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25
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Plaza-Díaz J, Ruiz-Ojeda FJ, Vilchez-Padial LM, Gil A. Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases. Nutrients 2017; 9:555. [PMID: 28555037 PMCID: PMC5490534 DOI: 10.3390/nu9060555] [Citation(s) in RCA: 272] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 05/18/2017] [Accepted: 05/24/2017] [Indexed: 12/11/2022] Open
Abstract
Probiotics and synbiotics are used to treat chronic diseases, principally due to their role in immune system modulation and the anti-inflammatory response. The present study reviewed the effects of probiotics and synbiotics on intestinal chronic diseases in in vitro, animal, and human studies, particularly in randomized clinical trials. The selected probiotics exhibit in vitro anti-inflammatory properties. Probiotic strains and cell-free supernatants reduced the expression of pro-inflammatory cytokines via action that is principally mediated by toll-like receptors. Probiotic administration improved the clinical symptoms, histological alterations, and mucus production in most of the evaluated animal studies, but some results suggest that caution should be taken when administering these agents in the relapse stages of IBD. In addition, no effects on chronic enteropathies were reported. Probiotic supplementation appears to be potentially well tolerated, effective, and safe in patients with IBD, in both CD and UC. Indeed, probiotics such as Bifidobacterium longum 536 improved the clinical symptoms in patients with mild to moderate active UC. Although it has been proposed that probiotics can provide benefits in certain conditions, the risks and benefits should be carefully assessed before initiating any therapy in patients with IBD. For this reason, further studies are required to understand the precise mechanism by which probiotics and synbiotics affect these diseases.
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Affiliation(s)
- Julio Plaza-Díaz
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada 18071, Spain.
- Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, Armilla, Granada 18016, Spain.
- Instituto de Investigación Biosanitaria ibs., GRANADA, Complejo Hospitalario Universitario de Granada, Granada 18014, Spain.
| | - Francisco Javier Ruiz-Ojeda
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada 18071, Spain.
- Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, Armilla, Granada 18016, Spain.
- Instituto de Investigación Biosanitaria ibs., GRANADA, Complejo Hospitalario Universitario de Granada, Granada 18014, Spain.
| | - Laura Maria Vilchez-Padial
- Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, Armilla, Granada 18016, Spain.
| | - Angel Gil
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada 18071, Spain.
- Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, Armilla, Granada 18016, Spain.
- Instituto de Investigación Biosanitaria ibs., GRANADA, Complejo Hospitalario Universitario de Granada, Granada 18014, Spain.
- CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.
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26
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Lu ZJ, Wu JJ, Jiang WL, Xiao JH, Tao KZ, Ma L, Zheng P, Wan R, Wang XP. MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression. World J Gastroenterol 2017; 23:976-985. [PMID: 28246471 PMCID: PMC5311107 DOI: 10.3748/wjg.v23.i6.976] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 11/27/2016] [Accepted: 12/19/2016] [Indexed: 02/06/2023] Open
Abstract
AIM
To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis.
METHODS
A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3’-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain- and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry.
RESULTS
MiR-155 directly bound to the 3’-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and pro-inflammatory secretions including IL-6, TNF-α, IL-1β, and IFN-γ, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and inflammatory response, were observed in the antagomiR-155-treated mice.
CONCLUSION
MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
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MESH Headings
- 3' Untranslated Regions
- Animals
- Antagomirs/administration & dosage
- Antagomirs/therapeutic use
- Blotting, Western
- Colitis, Ulcerative/chemically induced
- Colitis, Ulcerative/drug therapy
- Colitis, Ulcerative/metabolism
- Cytokines/metabolism
- Dextran Sulfate/toxicity
- Disease Models, Animal
- Down-Regulation
- Female
- Immunohistochemistry
- Mice
- Mice, Inbred BALB C
- MicroRNAs/metabolism
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/genetics
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/metabolism
- Primary Cell Culture
- Proto-Oncogene Proteins c-akt/metabolism
- RAW 264.7 Cells
- RNA Interference
- RNA, Small Interfering
- Signal Transduction
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27
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Di Luccia B, Manzo N, Baccigalupi L, Calabrò V, Crescenzi E, Ricca E, Pollice A. Lactobacillus gasseri SF1183 affects intestinal epithelial cell survival and growth. PLoS One 2013. [PMID: 23894414 DOI: 10.1016/j.jff.2017.12.049] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
It is now commonly accepted that the intestinal microbiota plays a crucial role in the gut physiology and homeostasis, and that both qualitative and quantitative alterations in the compositions of the gut flora exert profound effects on the host's intestinal cells. In spite of this, the details of the interaction between commensal bacteria and intestinal cells are still largely unknown and only in few cases the molecular mechanisms have been elucidated. Here we analyze the effects of molecules produced and secreted by Lactobacillus gasseri SF1183 on human intestinal HCT116 cells. L. gasseri is a well known species of lactic acid bacteria, commonly associated to the human intestine and SF1183 is a human strain previously isolated from an ileal biopsy of an healthy volunteer. SF1183 produces and secretes, in a growth phase-dependent way, molecule(s) able to drastically interfere with HCT116 cell proliferation. Although several attempts to purify and identify the bioactive molecule(s) have been so far unsuccessful, a partial characterization has indicated that it is smaller than 3 kDa, thermostable and of proteinaceous nature. L. gasseri molecule(s) stimulate a G1-phase arrest of the cell cycle by up-regulation of p21WAF1 rendering cells protected from intrinsic and extrinsic apoptosis. A L. gasseri-mediated reduction of apoptosis and of cell proliferation could be relevant in protecting epithelial barrier integrity and helping in reconstituting tissutal homeostasis.
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Affiliation(s)
- Blanda Di Luccia
- Department of Biology, University of Naples Federico II-MSA-Via Cinthia, Naples, Italy
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