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Li YR, Shen X, Zhu Y, Lyu Z, Yang L. The microbiota shapes the life trajectory of mucosal-associated invariant T cells. Trends Microbiol 2025:S0966-842X(25)00107-6. [PMID: 40280795 DOI: 10.1016/j.tim.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 03/21/2025] [Accepted: 03/25/2025] [Indexed: 04/29/2025]
Abstract
Mucosal-associated invariant T (MAIT) cells are innate-like T cells predominantly located in barrier tissues such as the lung, liver, skin, and colon. These cells recognize metabolites derived from the riboflavin biosynthetic pathway, which can rapidly traverse epithelial barriers and be presented during MAIT cell differentiation in the thymus and maturation in peripheral tissues. Furthermore, microbial metabolites significantly influence MAIT cell functions in various conditions, including cancer. This review summarizes how the microbiota shapes the life trajectory of MAIT cells and their antitumor reactivity. Additionally, we discuss the therapeutic implications of manipulating the microbiota as a 'bug-drug' strategy to enhance MAIT cell antitumor immunity, particularly in mucosal cancers, while emphasizing challenges and future directions for integrating microbiota considerations into MAIT cell-based therapies.
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Affiliation(s)
- Yan-Ruide Li
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
| | - Xinyuan Shen
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Yichen Zhu
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Zibai Lyu
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Lili Yang
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA; Goodman-Luskin Microbiome Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
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2
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Xiao Y, Yue X, Zhang X, Yang Y, Zhang Y, Sun L. The role of bacteriophage in inflammatory bowel disease and its therapeutic potential. Crit Rev Microbiol 2025:1-15. [PMID: 40219702 DOI: 10.1080/1040841x.2025.2492154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 03/25/2025] [Accepted: 04/07/2025] [Indexed: 04/14/2025]
Abstract
Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.
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Affiliation(s)
- Yuyang Xiao
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xinyu Yue
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xupeng Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yifei Yang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yibo Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Lang Sun
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
- Department of Microbiology, Xiangya School of the Basic Medical Science, Central South University, Changsha, Hunan Province, China
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3
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Zhao X, Xu J, Wu D, Chen N, Liu Y. Gut Microbiota in Different Treatment Response Types of Crohn's Disease Patients Treated with Biologics over a Long Disease Course. Biomedicines 2025; 13:708. [PMID: 40149684 PMCID: PMC11940770 DOI: 10.3390/biomedicines13030708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/06/2025] [Accepted: 03/11/2025] [Indexed: 03/29/2025] Open
Abstract
Background and Aims: Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with a globally increasing prevalence, partially driven by alterations in gut microbiota. Although biological therapy is the first-line treatment for CD, a significant proportion of patients experience a primary non-response or secondary loss of response over time. This study aimed to explore the differences in gut microbiota among CD patients with divergent long-term responses to biological therapy, focusing on a long disease course. Methods: Sixteen CD patients who applied the biological agents for a while were enrolled in this study and were followed for one year, during which fecal specimens were collected monthly. Metagenomic analysis was used to determine the microbiota profiles in fecal samples. The response to biological therapy was evaluated both endoscopically and clinically. Patients were categorized into three groups based on their response: R (long-term remission), mA (mild active), and R2A group (remission to active). The differences in the gut microbiota among the groups were analyzed. Results: Significant differences in fecal bacterial composition were observed between the groups. The R2A group exhibited a notable decline in gut microbial diversity compared to the other two groups (p < 0.05). Patients in the R group had higher abundances of Akkermansia muciniphila, Bifidobacterium adolescentis, and Megasphaera elsdenii. In contrast, Veillonella parvula, Veillonella atypica, and Klebsiella pneumoniae were higher in the R2A group. Conclusions: Gut microbial diversity and specific bacterial significantly differed among groups, reflecting distinct characteristics between responders and non-responders.
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Affiliation(s)
- Xiaolei Zhao
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China;
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Jun Xu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China;
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Dong Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing 100730, China;
| | - Ning Chen
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China;
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China;
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
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Sharma B, Agriantonis G, Twelker K, Ebelle D, Kiernan S, Siddiqui M, Soni A, Cheerasarn S, Simon W, Jiang W, Cardona A, Chapelet J, Agathis AZ, Gamboa A, Dave J, Mestre J, Bhatia ND, Shaefee Z, Whittington J. Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD). Int J Mol Sci 2025; 26:2503. [PMID: 40141145 PMCID: PMC11942158 DOI: 10.3390/ijms26062503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/03/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, and microbial factors. Recent evidence highlights the gut microbiota as a pivotal biomarker and modulator in IBD pathogenesis. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. A consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) and secondary bile acids, critical for gut homeostasis, alongside elevated pro-inflammatory metabolites. The gut microbiota interacts with host immune pathways, influencing morphogens, glycosylation, and podoplanin (PDPN) expression. The disruption of glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, microbial alterations contribute to oxidative stress, further destabilizing intestinal barriers. These molecular and cellular disruptions underscore the role of the microbiome in IBD pathophysiology. Emerging therapeutic strategies, including probiotics, prebiotics, and dietary interventions, aim to restore microbial balance and mitigate inflammation. Advanced studies on microbiota-targeted therapies reveal their potential to reduce disease severity and improve patient outcomes. Nevertheless, further research is needed to elucidate the bidirectional interactions between the gut microbiome and host immune responses and to translate these insights into clinical applications. This review consolidates current findings on the gut microbiota's role in IBD, emphasizing its diagnostic and therapeutic implications, and advocates for the continued exploration of microbiome-based interventions to combat this debilitating disease.
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Affiliation(s)
- Bharti Sharma
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - George Agriantonis
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Kate Twelker
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Danielle Ebelle
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Samantha Kiernan
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
| | - Maham Siddiqui
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Aditi Soni
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Sittha Cheerasarn
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
| | - Whenzdjyny Simon
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Winston Jiang
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Angie Cardona
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
| | - Jessica Chapelet
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Alexandra Z. Agathis
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Alejandro Gamboa
- Department of Medicine, Medical University of the Americas, Devens, MA 01434, USA;
| | - Jasmine Dave
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Juan Mestre
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Navin D. Bhatia
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Zahra Shaefee
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Jennifer Whittington
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
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El Mouzan M, Al Mofarreh M, Alsaleem B, Al Sarkhy A, Alanazi A, Khormi M, Almasoud A, Assiri A. Bacterial dysbiosis in newly diagnosed treatment naïve pediatric ulcerative colitis in Saudi Arabia. Saudi J Gastroenterol 2025; 31:14-21. [PMID: 38708883 PMCID: PMC11804967 DOI: 10.4103/sjg.sjg_66_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 03/29/2024] [Accepted: 04/01/2024] [Indexed: 05/07/2024] Open
Abstract
BACKGROUND The role of microbiota in the pathogenesis of ulcerative colitis (UC) has been increasingly recognized. However, most of the reports are from Western populations. In Middle Eastern countries, including Saudi Arabia, little is known about the role of microbiota. Therefore, our aim was to describe the bacterial microbiota profile and signature in pediatric UC in Saudi Arabia. METHODS Twenty children with UC and 20 healthy controls enrolled in the study gave stool samples. Twenty rectal mucosal samples were taken from UC and 20 from non-UC controls. Inclusion criteria included newly diagnosed and untreated children and lack of antibiotic exposure for at least 6 months before stool collection was required for children with UC and controls. Bacterial deoxyribonucleic acid was extracted and sequenced using shotgun metagenomic analysis. Statistical analysis included Shannon alpha diversity metrics, Bray-Curtis dissimilarity, DESeq2, and biomarker discovery. RESULTS The demographic characteristics were similar in children with UC and controls. There was a significant reduction in alpha diversity ( P = 0.037) and beta diversity in samples from children with UC ( P = 0.001). Many taxa were identified with log2 abundance analysis, revealing 110 and 102 species significantly depleted and enriched in UC, respectively. Eleven bacterial species' signatures were identified. CONCLUSIONS In Saudi Arabian children with UC, we demonstrate a dysbiosis similar to reports from Western populations, possibly related to changes of lifestyle. Microbial signature discovery in this report is an important contribution to research, leading to the development of adjunctive non-invasive diagnostic options in unusual cases of UC.
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Affiliation(s)
- Mohammad El Mouzan
- Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | | | - Badr Alsaleem
- King Fahad Medical City, Intestinal Failure Program, Riyadh, Saudi Arabia
| | - Ahmed Al Sarkhy
- Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Aziz Alanazi
- King Abdullah Specialized Children Hospital, Gastroenterology Unit, National Guard, Riyadh, Saudi Arabia
| | - Musa Khormi
- Pediatric Gastroenterology, King Saud Medical City, Riyadh-1 Health Cluster, Riyadh, Saudi Arabia
| | - Abdullah Almasoud
- Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Asaad Assiri
- Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Makdoumi K, Ayoub L, Bryngelsson IL, Graff P, Wiebert P, Vihlborg P. The risk for ophthalmological conditions in ulcerative colitis: A population-based case-control study. Is silica dust-exposure associated with inflammatory eye disease? Acta Ophthalmol 2024; 102:828-835. [PMID: 38738471 DOI: 10.1111/aos.16708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 04/30/2024] [Indexed: 05/14/2024]
Abstract
PURPOSE To study the risk for eye diseases in individuals with Ulcerative Colitis (UC), and to assess whether silica dust-exposure could contribute to the development of inflammatory eye diseases. METHODS A case-control study was conducted using a patient register processed by the National Board of Health and Welfare (NBHW) and Statistics Sweden. Cases were diagnosed with UC between 2007 and 2016. Matching was done with two random controls having the same age, sex and county of residence, without a systemic inflammatory disease. Using a job-exposure matrix, cases and controls were assessed for work-related silica dust exposure. The risk for eye disease was estimated by Cox regression analysis with calculation of Hazard Ratio (HR). RESULTS A total of 58 989 individuals were included, comprising 19 663 cases and 39 326 controls. The sex distribution was similar. Overall, individuals with UC had an increased risk for eye disease, specified in ICD 10 chapter VII (H00-H59) with HR 1.25 (CI 1.20-1.32). The highest HR on block-level for cases was 1.52 (CI 1.36-1.70), (H15-H22), which includes episcleritis, keratitis and anterior uveitis. The risk for ocular disease was higher in silica dust-exposed than non-exposed with a HR of 1.44 (CI 1.16-1.78) and 1.25 (CI 1.19-1.31), respectively. Among cases, the risk for iridocyclitis (H20) was further elevated by silica dust exposure, with HR of 3.84 (CI 1.64-8.97) in exposed compared to 1.94 (1.57-2.41) in non-exposed. CONCLUSION UC is associated with an increased risk for eye diseases, including inflammatory conditions. Our findings highlight that silica dust-exposure may be of importance in the pathogenesis of uveitis.
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Affiliation(s)
- Karim Makdoumi
- Department of Ophthalmology, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
| | - Lucyn Ayoub
- School of Medical Sciences, Orebro University, Orebro, Sweden
| | - Ing-Liss Bryngelsson
- Department of Ophthalmology, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
- Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
| | - Pål Graff
- National Institute of Occupational Health (STAMI), Oslo, Norway
| | - Pernilla Wiebert
- Unit of Occupational Medicine, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Center for Occupational and Environmental Medicine, Stockholm, Sweden
| | - Per Vihlborg
- Department of Geriatrics, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
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7
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Naito Y, Takagi T. Role of gut microbiota in inflammatory bowel disease pathogenesis. J Clin Biochem Nutr 2024; 75:175-177. [PMID: 39583974 PMCID: PMC11579855 DOI: 10.3164/jcbn.24-112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 08/30/2024] [Indexed: 11/26/2024] Open
Abstract
The role of the gut microbiota, especially bacterial flora, in the pathogenesis of inflammatory bowel disease (IBD) is becoming clearer. Advances in gut microbiota analysis and the use of gnotobiotics models have underscored the importance of gut bacteria and their metabolites in the progression of IBD. Fecal microbiota transplantation has shown promise in clinical trials for ulcerative colitis started as Advanced Medical Care B in Japan, raising expectations for its outcomes. This review explores the gut microbiota's role in IBD, encompassing both current knowledge and future prospects.
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Affiliation(s)
- Yuji Naito
- Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Tomohisa Takagi
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
- Department for Medical Innovation Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
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8
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Zhao Y, Chen Z, Dong R, Liu Y, Zhang Y, Guo Y, Yu M, Li X, Wang J. Multiomics analysis reveals the potential mechanism of high-fat diet in dextran sulfate sodium-induced colitis mice model. Food Sci Nutr 2024; 12:8309-8323. [PMID: 39479684 PMCID: PMC11521715 DOI: 10.1002/fsn3.4426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 11/02/2024] Open
Abstract
A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA-sequencing and RNA-seq technology. Results indicated that HFD-treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS-induced colitis, and HFD + DSS-treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6. These results provide valuable insights for determining potential therapeutic targets for addressing HFD-induced IBD.
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Affiliation(s)
- Yuyang Zhao
- Department of GastroenterologyChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
| | - Zhimin Chen
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Ruiyi Dong
- College of Physical Education, Hunan Normal UniversityChangshaChina
| | - Yufan Liu
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Yixin Zhang
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Yan Guo
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Meiyi Yu
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Xiang Li
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Jiangbin Wang
- Department of GastroenterologyChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
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9
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Urbauer E, Aguanno D, Mindermann N, Omer H, Metwaly A, Krammel T, Faro T, Remke M, Reitmeier S, Bärthel S, Kersting J, Huang Z, Xian F, Schmidt M, Saur D, Huber S, Stecher B, List M, Gómez-Varela D, Steiger K, Allez M, Rath E, Haller D. Mitochondrial perturbation in the intestine causes microbiota-dependent injury and gene signatures discriminative of inflammatory disease. Cell Host Microbe 2024; 32:1347-1364.e10. [PMID: 39013472 DOI: 10.1016/j.chom.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 05/13/2024] [Accepted: 06/20/2024] [Indexed: 07/18/2024]
Abstract
Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBDs). To understand how microbial-metabolic circuits contribute to intestinal injury, we disrupt mitochondrial function in the epithelium by deleting the mitochondrial chaperone, heat shock protein 60 (Hsp60Δ/ΔIEC). This metabolic perturbation causes self-resolving tissue injury. Regeneration is disrupted in the absence of the aryl hydrocarbon receptor (Hsp60Δ/ΔIEC;AhR-/-) involved in intestinal homeostasis or inflammatory regulator interleukin (IL)-10 (Hsp60Δ/ΔIEC;Il10-/-), causing IBD-like pathology. Injury is absent in the distal colon of germ-free (GF) Hsp60Δ/ΔIEC mice, highlighting bacterial control of metabolic injury. Colonizing GF Hsp60Δ/ΔIEC mice with the synthetic community OMM12 reveals expansion of metabolically flexible Bacteroides, and B. caecimuris mono-colonization recapitulates the injury. Transcriptional profiling of the metabolically impaired epithelium reveals gene signatures involved in oxidative stress (Ido1, Nos2, Duox2). These signatures are observed in samples from Crohn's disease patients, distinguishing active from inactive inflammation. Thus, mitochondrial perturbation of the epithelium causes microbiota-dependent injury with discriminative inflammatory gene profiles relevant for IBD.
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Affiliation(s)
- Elisabeth Urbauer
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Doriane Aguanno
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Nora Mindermann
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Hélène Omer
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Amira Metwaly
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Tina Krammel
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Tim Faro
- Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, 80337 Munich, Germany
| | - Marianne Remke
- Institute of Pathology, Technical University of Munich, 81675 Munich, Germany
| | - Sandra Reitmeier
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Stefanie Bärthel
- Division of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, 69120 Heidelberg, Germany; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 81675 Munich, Germany; Institute of Experimental Cancer Therapy, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany
| | - Johannes Kersting
- Data Science in Systems Biology, TUM School of Life Sciences, Technical University of Munich, Maximus-von-Imhof Forum 3, 85354 Freising, Germany
| | - Zihua Huang
- Data Science in Systems Biology, TUM School of Life Sciences, Technical University of Munich, Maximus-von-Imhof Forum 3, 85354 Freising, Germany
| | - Feng Xian
- Systems Biology of Pain, Division of Pharmacology & Toxicology, Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria
| | - Manuela Schmidt
- Systems Biology of Pain, Division of Pharmacology & Toxicology, Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria
| | - Dieter Saur
- Division of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, 69120 Heidelberg, Germany; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 81675 Munich, Germany; Institute of Experimental Cancer Therapy, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany
| | - Samuel Huber
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Bärbel Stecher
- Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig-Maximilians University of Munich, 80336 Munich, Germany; German Center for Infection Research, Partner site LMU Munich, 80336 Munich, Germany
| | - Markus List
- Data Science in Systems Biology, TUM School of Life Sciences, Technical University of Munich, Maximus-von-Imhof Forum 3, 85354 Freising, Germany; Munich Data Science Institute (MDSI), Technical University of Munich, 85748 Garching, Germany
| | - David Gómez-Varela
- Systems Biology of Pain, Division of Pharmacology & Toxicology, Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria
| | - Katja Steiger
- Institute of Pathology, Technical University of Munich, 81675 Munich, Germany
| | - Matthieu Allez
- Department of Gastroenterology, Hôpital Saint-Louis, APHP, INSERM UMRS 1160, Paris Diderot, Sorbonne Paris-Cité University, 75010 Paris, France
| | - Eva Rath
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany
| | - Dirk Haller
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany.
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Ray AK, Shukla A, Yadav A, Kaur U, Singh AK, Mago P, Bhavesh NS, Chaturvedi R, Tandon R, Shalimar, Kumar A, Malik MZ. A Comprehensive Pilot Study to Elucidate the Distinct Gut Microbial Composition and Its Functional Significance in Cardio-Metabolic Disease. Biochem Genet 2024:10.1007/s10528-024-10847-w. [PMID: 38839647 DOI: 10.1007/s10528-024-10847-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 05/21/2024] [Indexed: 06/07/2024]
Abstract
Cardio-metabolic disease is a significant global health challenge with increasing prevalence. Recent research underscores the disruption of gut microbial balance as a key factor in disease susceptibility. We aimed to characterize the gut microbiota composition and function in cardio-metabolic disease and healthy controls. For this purpose, we collected stool samples of 18 subjects (12 diseased, 6 healthy) and we performed metagenomics analysis and functional prediction using QIIME2 and PICRUSt. Furthermore, we carried out assessments of microbe-gene interactions, gene ontology, and microbe-disease associations. Our findings revealed distinct microbial patterns in the diseased group, particularly evident in lower taxonomic levels with significant variations in 14 microbial features. The diseased cohort exhibited an enrichment of Lachnospiraceae family, correlating with obesity, insulin resistance, and metabolic disturbances. Conversely, reduced levels of Clostridium, Gemmiger, and Ruminococcus genera indicated a potential inflammatory state, linked to compromised butyrate production and gut permeability. Functional analyses highlighted dysregulated pathways in amino acid metabolism and energy equilibrium, with perturbations correlating with elevated branch-chain amino acid levels-a known contributor to insulin resistance and type 2 diabetes. These findings were consistent across biomarker assessments, microbe-gene associations, and gene ontology analyses, emphasizing the intricate interplay between gut microbial dysbiosis and cardio-metabolic disease progression. In conclusion, our study unveils significant shifts in gut microbial composition and function in cardio-metabolic disease, emphasizing the broader implications of microbial dysregulation. Addressing gut microbial balance emerges as a crucial therapeutic target in managing cardio-metabolic disease burden.
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Affiliation(s)
- Ashwini Kumar Ray
- Department of Environmental Studies, University of Delhi, New Delhi, India.
| | - Avaneesh Shukla
- Department of Environmental Studies, University of Delhi, New Delhi, India
| | - Alka Yadav
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Urvinder Kaur
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Alok Kumar Singh
- Department of Zoology, Ramjas College, University of Delhi, New Delhi, India
| | - Payal Mago
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi, India
- Campus of Open Learning, University of Delhi, New Delhi, India
| | - Neel Sarovar Bhavesh
- International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Rupesh Chaturvedi
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Ravi Tandon
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Science, New Delhi, India
| | - Abhishek Kumar
- Manipal Academy of Higher Education (MAHE), Manipal, India
- Institute of Bioinformatics, International Technology Park, Whitefield, Bangalore, India
| | - Md Zubbair Malik
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait City, Kuwait.
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
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11
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Meng Q, Guo J, Lv K, Liu Y, Zhang J, Li M, Cheng X, Chen S, Huo X, Zhang Q, Chen Y, Li J. 5 S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner. Acta Pharm Sin B 2024; 14:2153-2176. [PMID: 38799623 PMCID: PMC11120280 DOI: 10.1016/j.apsb.2024.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 12/22/2023] [Accepted: 01/19/2024] [Indexed: 05/29/2024] Open
Abstract
Aberrant changes in the gut microbiota are implicated in many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity, indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD. Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies, novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed. Herein, we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone (an enantiomer) as a potent agent against experimental colitis that acts by modulating the gut microbiota. 5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids (SCFAs); thus, it regulates the intestinal immune system by reducing proinflammatory immune cell numbers, and maintains intestinal mucosal integrity by modulating tight junctions (TJs). Moreover, 5S-heudelotinone (2) ameliorates colitis-associated colorectal cancer (CAC) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced in situ carcinoma model. Together, these findings reveal the potential of a novel natural product, namely, 5S-heudelotinone, to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.
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Affiliation(s)
- Qing Meng
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Jianshuang Guo
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Ke Lv
- College of Chemistry and Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, Nankai University, Tianjin 300071, China
| | - Yang Liu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Jin Zhang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Mingyue Li
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Xirui Cheng
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Shenghua Chen
- College of Chemistry and Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, Nankai University, Tianjin 300071, China
| | | | - Quan Zhang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
| | - Yue Chen
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
- College of Chemistry and Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, Nankai University, Tianjin 300071, China
| | - Jing Li
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China
- College of Chemistry and Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, Nankai University, Tianjin 300071, China
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12
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Wang C, Gu Y, Chu Q, Wang X, Ding Y, Qin X, Liu T, Wang S, Liu X, Wang B, Cao H. Gut microbiota and metabolites as predictors of biologics response in inflammatory bowel disease: A comprehensive systematic review. Microbiol Res 2024; 282:127660. [PMID: 38442454 DOI: 10.1016/j.micres.2024.127660] [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: 07/25/2023] [Revised: 02/02/2024] [Accepted: 02/19/2024] [Indexed: 03/07/2024]
Abstract
Nonresponse to biologic agents in patients with inflammatory bowel disease (IBD) poses a significant public health burden, and the prediction of response to biologics offers valuable insights for IBD management. Given the pivotal role of gut microbiota and their endogenous metabolites in IBD, we conducted a systematic review to investigate the potential of fecal microbiota and mucosal microbiota and endogenous metabolomic markers as predictors for biotherapy response in IBD patients. A total of 38 studies were included in the review. Following anti-TNF-α treatment, the bacterial community characteristics of IBD patients exhibited a tendency to resemble those observed in healthy controls, indicating an improved clinical response. The levels of endogenous metabolites butyrate and deoxycholic acid were significantly associated with clinical remission following anti-TNF-α therapy. IBD patients who responded well to vedolizumab treatment had higher levels of specific bacteria that produce butyrate, along with increased levels of metabolites such as butyrate, branched-chain amino acids and acetamide following vedolizumab treatment. Crohn's disease patients who responded positively to ustekinumab treatment showed higher levels of Faecalibacterium and lower levels of Escherichia/Shigella. In conclusion, fecal microbiota and mucosal microbiota as well as their endogenous metabolites could provide a predictive tool for assessing the response of IBD patients to various biological agents and serve as a valuable reference for precise drug selection in clinical IBD patients.
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Affiliation(s)
- Chen Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yu Gu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Qiao Chu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Xin Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yiyun Ding
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Xiali Qin
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Sinan Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Xiang Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
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13
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Li S, Qian Q, Yang H, Wu Z, Xie Y, Yin Y, Cui Y, Li X. Fucoidan alleviated dextran sulfate sodium-induced ulcerative colitis with improved intestinal barrier, reshaped gut microbiota composition, and promoted autophagy in male C57BL/6 mice. Nutr Res 2024; 122:1-18. [PMID: 38064857 DOI: 10.1016/j.nutres.2023.11.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 11/11/2023] [Accepted: 11/12/2023] [Indexed: 03/08/2024]
Abstract
Although previous research has unveiled the remedial effects of fucoidan, an extract from marine algae, on ulcerative colitis (UC), the precise mechanisms remain elusive. Animal studies have suggested a connection between autophagy and the beneficial influences of fucoidan intervention. We hypothesized that fucoidan's alleviative effects on dextran sulfate sodium (DSS)-induced UC could be ascribed to autophagy. For our study, we chose 36 male C57BL/6 mice and administered 100 or 400 mg/(kg/body weight/day) of fucoidan via gavage for 5 consecutive weeks. During the last week, the mice were given 3% DSS in drinking water to induce UC. In contrast to the DSS-induced UC model, fucoidan intervention prevented DSS-induced body weight loss, mitigated colon shortening, improved colon mucosa damage, enhanced the intestinal barrier, and reduced serum inflammatory factor concentrations. Furthermore, fucoidan intervention reshaped the gut microbiota compositions, increased the relative abundance of Bacteroidota, Muribaculaceae_unclassified, Clostridiales_unclassified, and Lachnospiraceae_NK4A136_group, and decreased the relative abundance of Firmicutes, Proteobacteria, and Escherichia-Shigella, which led to a lower Firmicutes/Bacteroidota ratio. Additionally, fucoidan treatment enhanced autophagy, as evidenced by upregulated protein expressions of BECLIN1, ATG5, ATG7, and an increased microtubule-associated-proteinlight-chain-3-II/microtubule-associated-proteinlight-chain-3-I ratio. Our findings corroborated the ameliorating effects of fucoidan intervention on DSS-induced UC through autophagy activation, reorganization of gut microbiota, and fortification of the intestinal barrier. This lends support to the therapeutic potential of fucoidan as a natural bioactive ingredient for future UC treatments in humans.
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Affiliation(s)
- Shilan Li
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Qingfan Qian
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Hao Yang
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Zhengli Wu
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Yisha Xie
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Yan Yin
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Yuan Cui
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Xinli Li
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
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14
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Świrkosz G, Szczygieł A, Logoń K, Wrześniewska M, Gomułka K. The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis-A Literature Review. Biomedicines 2023; 11:3144. [PMID: 38137365 PMCID: PMC10740415 DOI: 10.3390/biomedicines11123144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/24/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. UC's pathogenesis involves colonic epithelial cell abnormalities and mucosal barrier dysfunction, leading to recurrent mucosal inflammation. The purpose of the article is to show the complex interplay between ulcerative colitis and the microbiome. The literature search was conducted using the PubMed database. After a screening process of studies published before October 2023, a total of 136 articles were selected. It has been discovered that there is a fundamental correlation of a robust intestinal microbiota and the preservation of gastrointestinal health. Dysbiosis poses a grave risk to the host organism. It renders the host susceptible to infections and has been linked to the pathogenesis of chronic diseases, with particular relevance to conditions such as ulcerative colitis. Current therapeutic strategies for UC involve medications such as aminosalicylic acids, glucocorticoids, and immunosuppressive agents, although recent breakthroughs in monoclonal antibody therapies have significantly improved UC treatment. Furthermore, modulating the gut microbiome with specific compounds and probiotics holds potential for inflammation reduction, while fecal microbiota transplantation shows promise for alleviating UC symptoms. This review provides an overview of the gut microbiome's role in UC pathogenesis and treatment, emphasizing areas for further research.
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Affiliation(s)
- Gabriela Świrkosz
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Aleksandra Szczygieł
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Katarzyna Logoń
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Martyna Wrześniewska
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Krzysztof Gomułka
- Clinical Department of Internal Medicine, Pneumology and Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland;
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15
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Xu P, Luo S, Song J, Dai Z, Li D, Wu C. Effect of sodium alginate-based hydrogel loaded with lutein on gut microbiota and inflammatory response in DSS-induced colitis mice. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
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16
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Liu J, Cai L, Yang R, Wei L, Luo H, Gui X. Risk of allergic rhinitis in patients with inflammatory bowel disease: A systematic review and meta-analysis. Allergol Immunopathol (Madr) 2023; 51:67-75. [PMID: 37937498 DOI: 10.15586/aei.v51i6.943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/22/2023] [Indexed: 11/09/2023]
Abstract
BACKGROUND Numerous parallels exist between inflammatory bowel disease (IBD) and allergic rhinitis (AR), which include risk factors (such as environmental and genetic factors), pathogenesis (immune disorders, epithelial cell barriers, etc.), and treatment (immunosuppressants and immunomodulators, such as cyclosporine and steroids). However, the risk of AR in IBD patients is unknown. OBJECTIVE In this systematic review and meta-analysis, patients with IBD are examined for their risk of AR. METHODS Several databases are accessible in both Chinese and English, including PubMed, BioRXiv, WanFang, the China National Knowledge Infrastructure (CNKI), Web of Science, METSTR, and MedRxiv. Findings presented at allergy, rhinology, thoracic, and gastrointestinal conferences were analyzed. Based on the inclusion and exclusion criteria, two evaluators independently retrieved data, read the literature, and evaluated bias risk. The data analysis was conducted using RevMan 5.4. Case-control and cohort studies were eligible study designs for this research. RESULTS There were 10 case-control studies and 1 cohort study included in the meta-analysis. The experimental group consisted of 65,687 IBD patients, of whom 5838 had AR. A total of 345,176 participants without IBD were included in the control group, of whom 24,625 developed AR. The outcomes demonstrated that IBD patients had a higher risk of developing AR (odds ratio [OR] = 1.48, 95% confidence interval [CI] [1.12, 1.95], Z = 2.78, P = 0.005) than those without IBD. CONCLUSION The risk of AR is higher in IBD patients. Further investigation is required to determine the mechanism behind the association between AR and IBD.
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Affiliation(s)
- Jie Liu
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Lun Cai
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Rongrong Yang
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Liping Wei
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Huazheng Luo
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Xiongbin Gui
- Department of Otorhinolaryngology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China;
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17
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Weng S, Huang L, Cai B, He L, Wen S, Li J, Zhong Z, Zhang H, Huang C, Yang Y, Jiang Q, Liu F. Astragaloside IV ameliorates experimental autoimmune myasthenia gravis by regulating CD4 + T cells and altering gut microbiota. Chin Med 2023; 18:97. [PMID: 37542273 PMCID: PMC10403896 DOI: 10.1186/s13020-023-00798-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 07/10/2023] [Indexed: 08/06/2023] Open
Abstract
BACKGROUND Myasthenia gravis (MG) is an antibody-mediated autoimmune disease and its pathogenesis is closely related to CD4 + T cells. In recent years, gut microbiota is considered to play an important role in the pathogenesis of MG. Astragaloside IV (AS-IV) is one of the main active components extracted from Astragalus membranaceus and has immunomodulatory effects. To study the immunomodulatory effect of AS-IV and the changes of gut microbiota on experimental autoimmune myasthenia gravis (EAMG) mice, we explore the possible mechanism of AS-IV in improving MG. METHODS In this study, network pharmacology was utilized to screen the crucial targets of AS-IV in the treatment of MG. Subsequently, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify potential pathways through which AS-IV acts against MG. Furthermore, experimental investigations were conducted to validate the underlying mechanism of AS-IV in MG treatment. Before modeling, 5 mice were randomly selected as the control group (CFA group), and the other 10 were induced to EAMG model. These mice were randomly divided into EAMG group and EAMG + AS-IV group, n = 5/group. In EAMG + AS-IV group, AS-IV was administered by gavage. CFA and EAMG groups were given the same volume of PBS. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. At the last administration, the feces were collected for 16S RNA microbiota analysis. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected by flow cytometry. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA. Furthermore, fecal microbial transplantation (FMT) experiments were performed for exploring the influence of changed intestinal flora on EAMG. After EAMG model was induced, the mice were treated with antibiotics daily for 4 weeks to germ-free. Then germ-free EAMG mice were randomly divided into two groups: FMT EAMG group, FMT AS-IV group, n = 3/group. Fecal extractions from EAMG and EAMG + AS-IV groups as gathered above were used to administered daily to the respective groups for 4 weeks. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected at the last administration. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA. RESULTS The network pharmacology and KEGG pathway analysis revealed that AS-IV regulates T cell pathways, including T cell receptor signaling pathway and Th17 cell differentiation, suggesting its potential in improving MG. Further experimental verification demonstrated that AS-IV administration improved muscle strength and body weight, reduced the level of Th1 and Th17 cells, enhanced the level of Treg cells, and resulted in alterations of the gut microbiota, including changes in beta diversity, the Firmicutes/Bacteroidetes (F/B) ratio, and the abundance of Clostridia in EAMG mice. We further conducted FMT tests and demonstrated that the EAMG Abx-treated mice which were transplanted the feces of mice treated with AS-IV significantly alleviated myasthenia symptoms, reduced Th1 and Th17 cells levels, and increased Treg cell levels. CONCLUSION This study speculated that AS-IV ameliorates EAMG by regulating CD4 + T cells and altering the structure and species of gut microbiota of EAMG.
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Affiliation(s)
- Senhui Weng
- Department of Spleen and Stomach Diseases, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, China
- Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
- Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Linwen Huang
- Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Bingxing Cai
- Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Long He
- Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Guangzhou University of Chinese Medicine, No.16 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Shuting Wen
- Department of Spleen and Stomach Diseases, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, China
- Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
- Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Jinghao Li
- Department of Traditional Chinese Medicine of the Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528000, China
| | - Zhuotai Zhong
- Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
- Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Haiyan Zhang
- Department of Spleen and Stomach Diseases, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, China
| | - Chongyang Huang
- Department of Spleen and Stomach Diseases, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, China
| | - Yunying Yang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Guangzhou University of Chinese Medicine, No.16 Airport Road, Baiyun District, Guangzhou, 510422, China
| | - Qilong Jiang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Guangzhou University of Chinese Medicine, No.16 Airport Road, Baiyun District, Guangzhou, 510422, China.
| | - Fengbin Liu
- Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, No.12 Airport Road, Baiyun District, Guangzhou, 510422, China.
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Guangzhou University of Chinese Medicine, No.16 Airport Road, Baiyun District, Guangzhou, 510422, China.
- Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 2, Helongqi Road, Renhe Town, Baiyun District, Guangzhou, 510000, China.
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18
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Ashique S, Mishra N, Garg A, Sibuh BZ, Taneja P, Rai G, Djearamane S, Wong LS, Al-Dayan N, Roychoudhury S, Kesari KK, Slama P, Roychoudhury S, Gupta PK. Recent updates on correlation between reactive oxygen species and synbiotics for effective management of ulcerative colitis. Front Nutr 2023; 10:1126579. [PMID: 37545572 PMCID: PMC10400011 DOI: 10.3389/fnut.2023.1126579] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 06/30/2023] [Indexed: 08/08/2023] Open
Abstract
Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects.
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Affiliation(s)
- Sumel Ashique
- Department of Pharmaceutics, Pandaveswar School of Pharmacy, Pandaveswar, West Bengal, India
| | - Neeraj Mishra
- Amity Institute of Pharmacy, Amity University Madhya Pradesh, Gwalior, India
| | - Ashish Garg
- Department of P.G. Studies and Research in Chemistry and Pharmacy, Rani Durgavati University, Jabalpur, India
| | - Belay Zeleke Sibuh
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Pankaj Taneja
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Gopal Rai
- Department of Pharmaceutics, Guru Ramdas Institute of Science and Technology, Jabalpur, India
| | - Sinouvassane Djearamane
- Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Malaysia
| | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia
| | - Noura Al-Dayan
- Department of Medical Lab Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | | | - Kavindra Kumar Kesari
- Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia
- Department of Applied Physics, Aalto University, Espoo, Finland
| | - Petr Slama
- Laboratory of Animal Immunology and Biotechnology, Department of Animal Morphology, Physiology and Genetics, Faculty of AgriSciences, Mendel University in Brno, Brno, Czechia
| | | | - Piyush Kumar Gupta
- Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, India
- Department of Biotechnology, Graphic Era Deemed to be University, Dehradun, India
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19
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Du C, Li Z, Zhang J, Yin N, Tang L, Li J, Sun J, Yu X, Chen W, Xiao H, Wu X, Chen X. The protective effect of carnosic acid on dextran sulfate sodium-induced colitis based on metabolomics and gut microbiota analysis. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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20
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Pagnini C, Di Paolo MC, Urgesi R, Pallotta L, Fanello G, Graziani MG, Delle Fave G. Safety and Potential Role of Lactobacillus rhamnosus GG Administration as Monotherapy in Ulcerative Colitis Patients with Mild-Moderate Clinical Activity. Microorganisms 2023; 11:1381. [PMID: 37374884 DOI: 10.3390/microorganisms11061381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 04/30/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. Lactobacillus rhamnosus GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild-moderate disease. The UC patients with mild-moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 1010 CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy (n = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition (p < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild-moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).
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Affiliation(s)
- Cristiano Pagnini
- Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy
| | - Maria Carla Di Paolo
- Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy
| | - Riccardo Urgesi
- Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy
| | - Lorella Pallotta
- Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy
| | - Gianfranco Fanello
- Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy
| | - Maria Giovanna Graziani
- Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy
| | - Gianfranco Delle Fave
- Department of Gastroenterology, "Sapienza" University of Rome, 00185 Rome, Italy
- Onlus "S. Andrea", 00199 Rome, Italy
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21
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Wu J, Guo W, Cui S, Tang X, Zhang Q, Lu W, Jin Y, Zhao J, Mao B, Chen W. Broccoli seed extract rich in polysaccharides and glucoraphanin ameliorates DSS-induced colitis via intestinal barrier protection and gut microbiota modulation in mice. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:1749-1760. [PMID: 36495024 DOI: 10.1002/jsfa.12382] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 11/05/2022] [Accepted: 12/10/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND Broccoli has received widespread attention because of its anti-inflammatory and antioxidant effects. The present study aimed to explore the composition of broccoli seed extract (BSE) and its effect on colitis induced by dextran sulfate sodium (DSS). RESULTS BSE mainly comprises glucoraphanin and polysaccharides composed of arabinose, galactose, glucose and mannose. Animal experiments suggested that BSE intervention effectively reversed body weight loss, suppressed the levels of proinflammatory interleukin-6, tumor necrosis factor-α and interleukin-1β, and elevated the levels of anti-inflammatory interleukin-10 and the activities of superoxide dismutase and glutathione in DSS-induced colitis mice. According to histopathologic and immunohistochemical analysis of colon tissue, BSE intervention may repair the intestinal barrier by upregulating mRNA levels and the expression of tight junction proteins (claudin-1, occludin and zonula occludens-1). Gas chromatography-mass spectrometry (MS) analysis demonstrated that cecal short-chain fatty acids in mice with BSE administration were significantly increased compared with the model group. Sulforaphane and sulforaphane-N-acetylcysteine were only detected in BSE group mice by ultra-performance liquid chromatography-MS analysis. In addition, BSE intervention evidently increased the abundance of Alistipeds, Coriobacteriaceae UCG-002 and Bifidobacterium and decreased the abundance of Escheichia-Shinella, Lachnospiraceae others, Parabacteroides, Ruminococcaceae others and Turicibacter, which possibly promoted carbohydrate metabolism and short-chain fatty acid production. CONCLUSION The present study aimed to elucidate the effect of BSE on colitis and found that BSE, as a novel food ingredient, has great potential for the improvement of colitis. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Jiaying Wu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Weiling Guo
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Shumao Cui
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xin Tang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
| | - Yan Jin
- The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, Wuxi, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Bingyong Mao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
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22
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Onwuzo S, Boustany A, Saleh M, Gupta R, Onwuzo C, Mascarenhas Monteiro J, Lawrence F, Obuekwe C, Morani Z, Asaad I. Increased Risk of Non-Alcoholic Steatohepatitis in Patients With Inflammatory Bowel Disease: A Population-Based Study. Cureus 2023; 15:e35854. [PMID: 36911589 PMCID: PMC9995222 DOI: 10.7759/cureus.35854] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2023] [Indexed: 03/09/2023] Open
Abstract
Background and objective The global health burden of inflammatory bowel disease (IBD) stems from its increasing incidence over the years. Comprehensive studies on the topic hypothesize that IBD plays a more dominant in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In light of this, we conducted this study with the aim of assessing the prevalence and risk factors of developing NASH in patients who have had a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). Methodology A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized for conducting this study. Patients aged 18-65 years were included. Pregnant patients and individuals diagnosed with alcohol use disorder were excluded. The risk of developing NASH was calculated using a multivariate regression analysis to account for potential confounding variables including male gender, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), and obesity. A two-sided p-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results A total of 79,346,259 individuals were screened in the database and 46,667,720 were selected for the final analysis based on the inclusion and exclusion criteria. Using multivariate regression analysis, the risk of developing NASH among patients with UC and CD was calculated. The odds of having NASH among patients with UC was 2.37 (95% CI: 2.17-2.60, p<0.001). Similarly, the odds of having NASH were high in patients with CD as well, at 2.79 (95% CI: 2.58-3.02, p<0.001). Conclusion Based on our findings, patients with IBD have an increased prevalence and higher odds of developing NASH after controlling for common risk factors. We believe that a complex pathophysiological relationship exists between both disease processes. Further research is required to establish appropriate screening times to enable earlier disease identification and thereby improve patient outcomes.
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Affiliation(s)
| | | | - Mustafa Saleh
- Faculty of Medical Sciences, Lebanese University, Beirut, LBN
| | - Riya Gupta
- Faculty of Medicine, Kasturba Medical College, Mangalore, IND
| | - Chidera Onwuzo
- Internal Medicine, General Hospital Lagos Island, Lagos, NGA
| | | | - Favour Lawrence
- Internal Medicine, General Hospital Lagos Island, Lagos, NGA
| | | | - Zoya Morani
- Medicine, Washington University of Health and Science, San Pedro, BLZ
| | - Imad Asaad
- Internal Medicine, Cleveland Clinic Foundation, Cleveland, USA
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23
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Reiss Z, Rob F, Kolar M, Schierova D, Kreisinger J, Jackova Z, Roubalova R, Coufal S, Mihula M, Thon T, Bajer L, Novakova M, Vasatko M, Kostovcikova K, Galanova N, Lukas M, Kverka M, Tresnak Hercogova J, Tlaskalova-Hogenova H, Jiraskova Zakostelska Z. Skin microbiota signature distinguishes IBD patients and reflects skin adverse events during anti-TNF therapy. Front Cell Infect Microbiol 2023; 12:1064537. [PMID: 36704107 PMCID: PMC9872723 DOI: 10.3389/fcimb.2022.1064537] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 12/01/2022] [Indexed: 01/11/2023] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where the role of gut but not skin dysbiosis is well recognized. Inhibitors of TNF have been successful in IBD treatment, but up to a quarter of patients suffer from unpredictable skin adverse events (SkAE). For this purpose, we analyzed temporal dynamics of skin microbiota and serum markers of inflammation and epithelial barrier integrity during anti-TNF therapy and SkAE manifestation in IBD patients. We observed that the skin microbiota signature of IBD patients differs markedly from healthy subjects. In particular, the skin microbiota of CD patients differs significantly from that of UC patients and healthy subjects, mainly in the retroauricular crease. In addition, we showed that anti-TNF-related SkAE are associated with specific shifts in skin microbiota profile and with a decrease in serum levels of L-FABP and I-FABP in IBD patients. For the first time, we showed that shifts in microbial composition in IBD patients are not limited to the gut and that skin microbiota and serum markers of the epithelium barrier may be suitable markers of SkAE during anti-TNF therapy.
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Affiliation(s)
- Zuzana Reiss
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Filip Rob
- Department of Dermatovenerology, Second Faculty of Medicine, Charles University, University Hospital Bulovka, Prague, Czechia
| | - Martin Kolar
- IBD Clinical and Research Centre ISCARE a.s., Prague, Czechia
| | - Dagmar Schierova
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Jakub Kreisinger
- Department of Zoology, Faculty of Science, Charles University, Prague, Czechia
| | - Zuzana Jackova
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Radka Roubalova
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Stepan Coufal
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Martin Mihula
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Tomas Thon
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Lukas Bajer
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia,Department of Gastroenterology and Hepatology, Institute of Clinical and Experimental Medicine, Prague, Czechia
| | - Michaela Novakova
- Department of Dermatovenerology, Second Faculty of Medicine, Charles University, University Hospital Bulovka, Prague, Czechia
| | - Martin Vasatko
- IBD Clinical and Research Centre ISCARE a.s., Prague, Czechia
| | - Klara Kostovcikova
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Natalie Galanova
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Milan Lukas
- IBD Clinical and Research Centre ISCARE a.s., Prague, Czechia,Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czechia
| | - Miloslav Kverka
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Jana Tresnak Hercogova
- Department of Dermatovenerology, Second Faculty of Medicine, Charles University, University Hospital Bulovka, Prague, Czechia,Prof. Hercogova Dermatology, Prague, Czechia
| | | | - Zuzana Jiraskova Zakostelska
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia,*Correspondence: Zuzana Jiraskova Zakostelska,
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24
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Gut Microbiota in Non-Alcoholic Fatty Liver Disease Patients with Inflammatory Bowel Diseases: A Complex Interplay. Nutrients 2022; 14:nu14245323. [PMID: 36558483 PMCID: PMC9785319 DOI: 10.3390/nu14245323] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/10/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
The intestinal microbiota represents the microbial community that colonizes the gastrointestinal tract and constitutes the most complex ecosystem present in nature. The main intestinal microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucromicrobia, with a clear predominance of the two phyla Firmicutes and Bacteroidetes which account for about 90% of the intestinal phyla. Intestinal microbiota alteration, or dysbiosis, has been proven to be involved in the development of various syndromes, such as non-alcoholic fatty liver disease, Crohn's disease, and ulcerative colitis. The present review underlines the most recurrent changes in the intestinal microbiota of patients with NAFLD, Crohn's disease, and ulcerative colitis.
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25
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Wen Y, Zhang W, Yang R, Jiang L, Zhang X, Wang B, Hua Y, Ji P, Yuan Z, Wei Y, Yao W. Regulation of Yujin Powder alcoholic extracts on ILC3s-TD IgA-colonic mucosal flora axis of DSS-induced ulcerative colitis. Front Microbiol 2022; 13:1039884. [PMID: 36338041 PMCID: PMC9633017 DOI: 10.3389/fmicb.2022.1039884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/07/2022] [Indexed: 11/29/2022] Open
Abstract
The intestinal flora maintained by the immune system plays an important role in healthy colon. However, the role of ILC3s-TD IgA-colonic mucosal flora axis in ulcerative colitis (UC) and whether it could become an innovative pathway for the treatment of UC is unknown. Yujin Powder is a classic prescription for treatment of dampness-heat type intestine disease in traditional Chinese medicine and has therapeutic effects on UC. Hence, the present study aimed to investigate the regulatory mechanism of Yujin Powder alcoholic extracts (YJP-A) on UC via ILC3s-TD IgA-colonic mucosal flora axis. The UC mouse model was induced by drinking 3.5% dextran sodium sulfate (DSS), meanwhile, YJP-A was given orally for prevention. During the experiment, the clinical symptoms of mice were recorded. Then the intestinal injury and inflammatory response of mice about UC were detected after the experiment. In addition, the relevant indicators of ILC3s-TD IgA-colonic mucosal flora axis were detected. The results showed that YJP-A had good therapy effects on DSS-induced mice UC: improved the symptoms, increased body weight and the length of colon, decreased the disease activity index score, ameliorated the intestinal injury, and reduced the inflammation etc. Also, YJP-A significantly increased the ILC3s proportion and the expression level of MHC II; significantly decreased the proportion of Tfh cells and B cells and the expression levels of Bcl6, IL-4, Aicda in mesenteric lymph nodes of colon in UC mice and IgA in colon. In addition, by 16S rDNA sequencing, YJP-A could restore TD IgA targets colonic mucus flora in UC mice by decreasing the relative abundance of Mucispirillum, Lachnospiraceae and increasing the relative abundance of Allprevotella, Alistipes, and Ruminococcaceae etc. In conclusion, our results demonstrated that the ILC3s-TD IgA-colonic mucosal flora axis was disordered in UC mice. YJP-A could significantly promote the proliferation of ILC3s to inhibit Tfh responses and B cells class switching through MHC II, further to limit TD IgA responses toward colonic mucosal flora. Our findings suggested that this axis may be a novel and promising strategy to prevent UC.
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Affiliation(s)
- Yanqiao Wen
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Wangdong Zhang
- Laboratory of Veterinary Pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Rong Yang
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Lidong Jiang
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Xiaosong Zhang
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Baoshan Wang
- Laboratory of Veterinary Pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Yongli Hua
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Peng Ji
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Ziwen Yuan
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Yanming Wei
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
- *Correspondence: Yanming Wei; Wanling Yao,
| | - Wanling Yao
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
- *Correspondence: Yanming Wei; Wanling Yao,
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Bi Z, Cui E, Yao Y, Chang X, Wang X, Zhang Y, Xu GX, Zhuang H, Hua ZC. Recombinant Bifidobacterium longum Carrying Endostatin Protein Alleviates Dextran Sodium Sulfate-Induced Colitis and Colon Cancer in Rats. Front Microbiol 2022; 13:927277. [PMID: 35847065 PMCID: PMC9280188 DOI: 10.3389/fmicb.2022.927277] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/06/2022] [Indexed: 12/02/2022] Open
Abstract
Bifidobacterium has been widely administrated orally as probiotics to prevent pathogen colonization and modulate the gut microbiome balance. Endostatin is an endogenous inhibitor of angiogenesis and has been shown to inhibit tumor growth, invasion, and metastasis. At present, the combination of endostatin and chemotherapeutic drugs has been regarded as a promising antitumor treatment strategy. In this study, we selected a safe strain of Bifidobacterium longum as a delivery system to transport endostatin to the gastrointestinal tract and explored their combined effect on inflammatory bowel disease (IBD) and colitis-associated cancer. The results indicated that B. longum-Endo relieved dextran sulfate sodium-induced body weight loss, diarrhea, colon shortening, and epithelium damage. Long-term oral administration of B. longum-Endo significantly decreased tumor formation rate, tumor number, and tumor size. Moreover, the effect of B. longum-Endo on gut microbiota dysbiosis was also confirmed by 16S rRNA sequencing analysis. The levels of potentially beneficial bacteria, such as Lactobacillus, Bifidobacterium, Allobaculum, and Parabateroides, were increased in the B. longum-Endo group compared to the model and B. longum groups. Meanwhile, levels of potentially pathogenic bacteria including Desulfovibrio, Helicobacter, and Enterorhabdus were decreased. Taken together, these results suggested that oral administration of recombinant B. longum-Endo strain may be a promising therapeutic strategy for IBD and colitis-associated cancer.
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Affiliation(s)
- Zhiqian Bi
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
| | - Enqing Cui
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
| | - Yingying Yao
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
| | - Xiaoyao Chang
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
| | - Xiaoyang Wang
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
| | - Yuhui Zhang
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
| | - Gen-Xing Xu
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
- *Correspondence: Gen-Xing Xu,
| | - Hongqin Zhuang
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
- Hongqin Zhuang,
| | - Zi-Chun Hua
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, China
- Changzhou High-Tech Research Institute of Nanjing University, Changzhou, China
- Jiangsu Target Pharma Laboratories Inc., Changzhou, China
- School of Biopharmacy, China Pharmaceutical University, Nanjing, China
- Zi-Chun Hua,
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Zhang S, Liang Y, Yao J, Li DF, Wang LS. Role of Pyroptosis in Inflammatory Bowel Disease (IBD): From Gasdermins to DAMPs. Front Pharmacol 2022; 13:833588. [PMID: 35677444 PMCID: PMC9168461 DOI: 10.3389/fphar.2022.833588] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 04/22/2022] [Indexed: 12/11/2022] Open
Abstract
Pyroptosis is a pro-inflammatory cell death executed by gasdermin family proteins that involve the formation of pores on cells, recognition of danger signals, and release of pro-inflammatory cytokines IL-1β and IL-18. Pyroptosis modulates mucosal innate immunity and enteropathogenic bacterial infection. Similarly, the gasdermin family has been reported to be involved in the defense of the intestinal epithelium against bacterial infection and in the regulation of intestinal inflammation. Pyroptosis initiates damage signals that activate multiple pathways to cause inflammation, which may be a potential cause of chronic intestinal inflammation. In this review, we discuss the impact of pyroptosis on inflammatory bowel disease (IBD), with a focus on the executive proteins of pyroptosis (GSDMB, GADMD, and GSDME) and IBD-related endogenous damage-associated molecular patterns (DAMPs) produced by pyroptosis.
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Affiliation(s)
- Shuxia Zhang
- School of Medicine, Southern University of Science and Technology, Shenzhen People Hospital, Shenzhen, China
| | | | - Jun Yao
- Department of Gastroenterology, The Second Clinical Medicine College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
| | - De-Feng Li
- Department of Gastroenterology, The Second Clinical Medicine College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
| | - Li-Sheng Wang
- Department of Gastroenterology, The Second Clinical Medicine College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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Wu J, Wu Y, Chen Y, Liu M, Yu H, Zhang Y, Wang T. Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota. PLANTA MEDICA 2022; 88:559-569. [PMID: 34098585 DOI: 10.1055/a-1506-3476] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Ulcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.
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Affiliation(s)
- Jiaqi Wu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuzheng Wu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yue Chen
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Mengyang Liu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Haiyang Yu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yi Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Tao Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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29
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Aximujiang K, Kaheman K, Wushouer X, Wu G, Ahemaiti A, Yunusi K. Lactobacillus acidophilus and HKL Suspension Alleviates Ulcerative Colitis in Rats by Regulating Gut Microbiota, Suppressing TLR9, and Promoting Metabolism. Front Pharmacol 2022; 13:859628. [PMID: 35600873 PMCID: PMC9118348 DOI: 10.3389/fphar.2022.859628] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with complex pathogenesis. The intestinal flora disturbance affects the homeostasis of the intestinal environment, leading to metabolic imbalance and immune abnormalities of the host, contributing to the perpetuation of intestinal inflammation. We suggest that the combination of anti-inflammatory therapy and the regulation of intestinal flora balance may help in the treatment process. Previously, we used a combination treatment consisting of Lactobacillus acidophilus (Lac) and Chinese medicine Huan Kui Le (HKL) suspension in a UC rat model, where the combined intervention was more effective than either treatment alone. Herein, the mechanism of action of this combined treatment has been investigated using 16S rRNA sequencing, immunohistochemistry, and ELISA methods in the colon, and untargeted metabolomics profiling in serum. Colon protein expression levels of IL-13 and TGF-β were upregulated, whereas those of TLR9 and TLR4 were downregulated, consistent with an anti-inflammatory effect. In addition, gut microbiota structure changed, shown by a decrease in opportunistic pathogens correlated with intestinal inflammation, such as Klebsiella and Escherichia-Shigella, and an increase in beneficial bacteria such as Bifidobacterium. The latter correlated positively with IL-13 and TGF-β and negatively with IFN-γ. Finally, this treatment alleviated the disruption of the metabolic profile observed in UC rats by increasing short-chain fatty acid (SCFA)-producing bacteria in the colonic epithelium. This combination treatment also affected the metabolism of lactic acid, creatine, and glycine and inhibited the growth of Klebsiella. Overall, we suggest that treatment combining probiotics and traditional Chinese medicine is a novel strategy beneficial in UC that acts by modulating gut microbiota and its metabolites, TLR9, and cytokines in different pathways.
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Affiliation(s)
- Kasimujiang Aximujiang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
- College of Pharmacy, Xinjiang Medical University, Urumqi, China
| | - Kuerbannaimu Kaheman
- Department of Rehabilitation Medicine, First Affiliated Hospital in Xinjiang Medical University, Urumqi, China
| | - Xilinguli Wushouer
- Department of Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Guixia Wu
- Department of Physiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Abulaiti Ahemaiti
- The Functional Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Kurexi Yunusi
- Uygur Medical College, Xinjiang Medical University, Urumqi, China
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30
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Exploring the Gut Microbiome in Myasthenia Gravis. Nutrients 2022; 14:nu14081647. [PMID: 35458209 PMCID: PMC9027283 DOI: 10.3390/nu14081647] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/10/2022] [Accepted: 04/12/2022] [Indexed: 12/13/2022] Open
Abstract
The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host’s antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota’s relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG’s clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.
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31
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Xu P, Lv T, Dong S, Cui Z, Luo X, Jia B, Jeon CO, Zhang J. Association between intestinal microbiome and inflammatory bowel disease: insights from bibliometric analysis. Comput Struct Biotechnol J 2022; 20:1716-1725. [PMID: 35495114 PMCID: PMC9019919 DOI: 10.1016/j.csbj.2022.04.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 04/05/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
Intestinal microbiota has been increasingly studied in the field of IBD over the last 20 years. The gut microbiome, metabolites, and their corresponding host signaling pathways are highly associated with IBD. Probiotics may relieve IBD as a complementary therapy. The pathogenesis and treatment strategies of IBD need to be further studied. The gut microbiome is highly linked to inflammatory bowel disease (IBD). A total of 3890 publications related to the two terms from 2000 to 2020 were extracted from the Web of Science Core Collection to study the association from a bibliometric perspective. Publications on this topic have grown rapidly since 2008. The United States and Harvard University are the country and institution with the largest number of publications, respectively. Inflammatory Bowel Diseases is the most productive journal with 211 published articles. The most influential journal in this field is Gut with 13,359 citations. The co-citation analysis of references showed that the IBD-related topics with the highest focus are “gut microbiota,” “metagenomics,” “bacterial community,” “fecal microbiota transplantation,” “probiotics,” and “colitis-associated colorectal cancer.” Keyword cluster and keyword burst analyses showed that “gut microbiota,” “metagenomics,” and “fecal microbiota transplantation” are currently the most researched topics in the field of IBD. The literature in this field is mainly distributed between alterations of the intestinal microbiota, microbial metabolites, and related host signaling pathways. Probiotic treatment also frequently appears in literature. This bibliometric analysis can guide future research and promote the development of the field of gut microbiome and IBD.
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Zhang Y, Garrett S, Carroll RE, Xia Y, Sun J. Vitamin D receptor upregulates tight junction protein claudin-5 against colitis-associated tumorigenesis. Mucosal Immunol 2022; 15:683-697. [PMID: 35338345 PMCID: PMC9262815 DOI: 10.1038/s41385-022-00502-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 01/28/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023]
Abstract
Tight junctions are essential for barrier integrity, inflammation, and cancer. Vitamin D and the vitamin D receptor (VDR) play important roles in colorectal cancer (CRC). Using the human CRC database, we found colonic VDR expression was low and significantly correlated with a reduction of Claudin-5 mRNA and protein. In the colon of VDRΔIEC mice, deletion of intestinal VDR led to lower protein and mRNA levels of Claudin-5. Intestinal permeability was increased in the VDR-/- colon cancer model. Lacking VDR and a reduction of Claudin-5 are associated with an increased number of tumors in the VDR-/- and VDRΔIEC mice. Furthermore, gain and loss functional studies have identified CLDN-5 as a downstream target of VDR. We identified the Vitamin D response element (VDRE) binding sites in a reporter system showed that VDRE in the Claudin-5 promoter is required for vitamin D3-induced Claudin-5 expression. Conditional epithelial VDR overexpression protected against the loss of Claudin-5 in response to inflammation and tumorigenesis in vivo. We also reported fecal VDR reduction in a colon cancer model. This study advances the understanding of how VDR regulates intestinal barrier functions in tumorigenesis and the possibility for identifying new biomarker and therapeutic targets to restore VDR-dependent functions in CRC.
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Affiliation(s)
- Yongguo Zhang
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Shari Garrett
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA,Department of Microbiology/Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Robert E. Carroll
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Yinglin Xia
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Jun Sun
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA,UIC Cancer Center, University of Illinois at Chicago, Chicago, IL, USA,Department of Microbiology/Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA,Jesse Brown VA Medical Center Chicago, IL (537), USA
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Stalla FM, Astegiano M, Ribaldone DG, Saracco GM, Pellicano R. The small intestine: barrier, permeability and microbiota. Minerva Gastroenterol (Torino) 2022; 68:98-110. [PMID: 33267569 DOI: 10.23736/s2724-5985.20.02808-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In recent years, there has been growing interest in the comprehension of the physiology of intestinal permeability and microbiota; and how these elements could influence the pathogenesis of diseases. The term intestinal permeability describes all the processes that allow the passage of molecules as water, electrolytes and nutrients through the intestinal barrier by the paracellular or the transcellular transport systems with several implications for self-tolerance and not-self immunity. An increased permeability might induce a more significant interaction of the immune system with unknown external antigens. This might favor the onset of several immune-related extra-intestinal diseases including coeliac disease, diabetes mellitus type 1, bronchial asthma and inflammatory bowel diseases. Furthermore, the intestinal permeability interacts every day with microbiota, the complex system of mutualistic inhabitants and commensal microorganisms living in the healthy gut. Microbiota is implicated in physiological functions by actively participating in digestion, absorption, synthesis of vitamins and protection from external aggressions. The critical site where these processes occur is the small intestine to which this updated review is dedicated. Understanding its anatomy, its barrier structure and permeability modulation and its microbiota composition is the essential skill to comprehend the complex pathogenesis of several - not only gastroenterological - diseases.
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Affiliation(s)
| | | | | | - Giorgio M Saracco
- Department of Medical Sciences, University of Turin, Turin, Italy
- Unit of Gastroenterology, Molinette Hospital, Turin, Italy
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The role of enteric dysbacteriosis and modulation of gut microbiota in the treatment of inflammatory bowel disease. Microb Pathog 2021; 165:105381. [PMID: 34974123 DOI: 10.1016/j.micpath.2021.105381] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022]
Abstract
The incidence of inflammatory bowel disease (IBD) is globally increasing. This disorder seriously affects the quality of life in patients. Interestingly, studies have detected that the intestinal flora imbalance is a critical factor in the progression of IBD. One potential treatment strategy for IBD involves regulating the composition and function of the intestinal flora. To date, a multitude of experiments have confirmed the relationship between intestinal flora, immune regulation, and anti-inflammation. The intestinal flora can reduce intestinal inflammation by regulating immunity and increasing the secretion of metabolic short-chain fatty acids. In this review, we discuss the composition and function of the intestinal flora, the relationship between the intestinal flora and the host, the role of intestinal flora disorders in IBD, and the progress in IBD treatment. Combining the regulation of the intestinal flora with probiotics treatment is considered a promising strategy for substantially improving the treatment of IBD.
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35
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MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis. EBioMedicine 2021; 74:103751. [PMID: 34902790 PMCID: PMC8671112 DOI: 10.1016/j.ebiom.2021.103751] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/21/2021] [Accepted: 11/30/2021] [Indexed: 12/26/2022] Open
Abstract
The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.
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Liu H, Bian Z, Zhang Q, Xiao Z, Cao Y, Sun X, Qin Y, Mao L, Chu X, Liao W, Zha L, Sun S. Sodium butyrate inhibits colitis-associated colorectal cancer through preventing the gut microbiota dysbiosis and reducing the expression of NLRP3 and IL-1β. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Ćesić D, Lugović-Mihić L, Ferček I, Grginić AG, Jelić M, Bešlić I, Tambić Andrašević A. Salivary Microbiota Is Significantly Less Diverse in Patients with Chronic Spontaneous Urticaria Compared to Healthy Controls: Preliminary Results. Life (Basel) 2021; 11:life11121329. [PMID: 34947860 PMCID: PMC8707062 DOI: 10.3390/life11121329] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 11/27/2021] [Accepted: 11/29/2021] [Indexed: 11/21/2022] Open
Abstract
Background: Because of the important role in regulating the immune system, increasing evidence suggests a possible implication of gut microbiota in Chronic spontaneous urticaria (CSU). Although the oral cavity is the first site of contact between microbiota and the immune system, the association between salivary microbiota and CSU has not yet been reported. Objective: This case-control study aimed to compare differences in salivary microbiota between CSU patients and healthy controls (HC). Twenty-three participants—13 patients with CSU and 10 HC were enrolled; salivary microbiota was determined by molecular approach targeting 16S ribosomal RNA. Terminal restriction fragment length polymorphism (T-RFLP) analysis was performed. Results: Alpha diversity of salivary microbiota in CSU patients was significantly reduced compared to HC, resulting in alteration of the community composition. Species richness determined via the Shannon index was significantly reduced in the CSU group. Conclusion: Dysbiosis of salivary microbiota may contribute to a dysregulated immune system in the development of CSU. To our knowledge, this was the first study that reported an alteration in salivary microbiota composition in CSU patients.
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Affiliation(s)
- Diana Ćesić
- Department of Dermatology and Venereology, Sestre Milosrdnice University Hospital Centre, 10 000 Zagreb, Croatia; (L.L.-M.); (I.B.)
- School of Dental Medicine, University of Zagreb, 10 000 Zagreb, Croatia;
- Correspondence: ; Tel.: +385-98-977-0234
| | - Liborija Lugović-Mihić
- Department of Dermatology and Venereology, Sestre Milosrdnice University Hospital Centre, 10 000 Zagreb, Croatia; (L.L.-M.); (I.B.)
- School of Dental Medicine, University of Zagreb, 10 000 Zagreb, Croatia;
| | - Iva Ferček
- Department of Ophthalmology, Sestre Milosrdnice University Hospital Centre, 10 000 Zagreb, Croatia;
| | - Ana Gverić Grginić
- Department of Clinical Microbiology, Sestre Milosrdnice University Hospital Centre, 10 000 Zagreb, Croatia;
| | - Marko Jelić
- Department of Clinical Microbiology, University Hospital for Infectious Diseases, 10 000 Zagreb, Croatia;
| | - Iva Bešlić
- Department of Dermatology and Venereology, Sestre Milosrdnice University Hospital Centre, 10 000 Zagreb, Croatia; (L.L.-M.); (I.B.)
- School of Dental Medicine, University of Zagreb, 10 000 Zagreb, Croatia;
| | - Arjana Tambić Andrašević
- School of Dental Medicine, University of Zagreb, 10 000 Zagreb, Croatia;
- Department of Clinical Microbiology, University Hospital for Infectious Diseases, 10 000 Zagreb, Croatia;
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Kocot AM, Wróblewska B. Fermented products and bioactive food compounds as a tool to activate autophagy and promote the maintenance of the intestinal barrier function. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Sakai K, Sakurai T, De Velasco MA, Nagai T, Chikugo T, Ueshima K, Kura Y, Takahama T, Hayashi H, Nakagawa K, Kudo M, Nishio K. Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis. Front Oncol 2021; 11:763468. [PMID: 34778085 PMCID: PMC8578892 DOI: 10.3389/fonc.2021.763468] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/11/2021] [Indexed: 12/30/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.
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Affiliation(s)
- Kazuko Sakai
- Department of Genome Biology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Toshiharu Sakurai
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Marco A De Velasco
- Department of Genome Biology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Tomoyuki Nagai
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Takaaki Chikugo
- Department of Diagnostic Pathology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Yurie Kura
- Department of Genome Biology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Takayuki Takahama
- Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Hidetoshi Hayashi
- Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Kazuhiko Nakagawa
- Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Kazuto Nishio
- Department of Genome Biology, Faculty of Medicine, Kindai University, Osaka, Japan
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Kim D, Jung JY, Oh HS, Jee SR, Park SJ, Lee SH, Yoon JS, Yu SJ, Yoon IC, Lee HS. Comparison of sampling methods in assessing the microbiome from patients with ulcerative colitis. BMC Gastroenterol 2021; 21:396. [PMID: 34686128 PMCID: PMC8614001 DOI: 10.1186/s12876-021-01975-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 10/14/2021] [Indexed: 11/10/2022] Open
Abstract
Background Dysbiosis of ulcerative colitis (UC) has been frequently investigated using readily accessible stool samples. However, stool samples might insufficiently represent the mucosa-associated microbiome status. We hypothesized that luminal contents including loosely adherent luminal bacteria after bowel preparation may be suitable for diagnosing the dysbiosis of UC. Methods This study included 16 patients with UC (9 men and 7 women, mean age: 52.13 ± 14.09 years) and 15 sex- and age-matched healthy individuals (8 men and 7 women, mean age: 50.93 ± 14.11 years). They donated stool samples before colonoscopy and underwent luminal content aspiration and endoscopic biopsy during the colonoscopy. Then, the composition of each microbiome sample was analyzed by 16S rRNA-based next-generation sequencing. Results The microbiome between stool, luminal contents, and biopsy was significantly different in alpha and beta diversities. However, a correlation existed between stool and luminal contents in the Procrustes test (p = 0.001) and Mantel test (p = 0.0001). The stool microbiome was different between patients with UC and the healthy controls. Conversely, no difference was found in the microbiome of luminal content and biopsy samples between the two subject groups. The microbiome of stool and lavage predicted UC, with AUC values of 0.85 and 0.81, respectively. Conclusion The microbiome of stool, luminal contents, and biopsy was significantly different. However, the microbiome of luminal contents during colonoscopy can predict UC, with AUC values of 0.81. Colonoscopic luminal content aspiration analysis could determine microbiome differences between patients with UC and the healthy control, thereby beneficial in screening dysbiosis via endoscopy. Trial registration: This trial was registered at http://cris.nih.go.kr. Registration No.: KCT0003352), Date: 2018–11-13.
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Affiliation(s)
- Dan Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - Jun-Young Jung
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - Hyun-Seok Oh
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea.,ChunLab Inc, Seoul, 06725, Korea
| | - Sam-Ryong Jee
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - Sung Jae Park
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - Sang-Heon Lee
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - Jun-Sik Yoon
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - Seung Jung Yu
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea
| | - In-Cheol Yoon
- Department of Gastroenterology, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea
| | - Hong Sub Lee
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Korea.
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YAMAMOTO M, OHMORI H, TAKEI D, MATSUMOTO T, TAKEMOTO M, IKEDA M, SUMIMOTO R, KOBAYASHI T, OHDAN H. Clostridium butyricum affects nutrition and immunology by modulating gut microbiota. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2021; 41:30-36. [PMID: 35433162 PMCID: PMC8970657 DOI: 10.12938/bmfh.2021-046] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/29/2021] [Indexed: 11/05/2022]
Abstract
The gut microbiota has nutritional and protective functions. In patients with end-stage renal disease, changes in the gut microbiota disrupt their protective functions. Probiotics help maintain normal bowel function. However, their role in patients with end-stage renal disease is controversial. We investigated whether Clostridium butyricum affects the nutrition and immune function of patients with end-stage renal disease undergoing maintenance dialysis between 2014 and 2015; thirty-seven patients were included. The patients were divided into two groups: one in which C. butyricum was administered and one in which it was not. One tablet of the probiotics, which contained 20 mg of C. butyricum, was administered orally three times daily for 2 years in the C. butyricum group. The 16S rRNA genes were sequenced from stool samples of 14 (37.8%) patients in the C. butyricum group and 23 (62.2%) patients in the control group. The differences in the gut microbiota of the two groups were analyzed. The α-diversity index indicated that the C. butyricum group had significantly more operational taxonomic units and higher albumin and transferrin levels than the control group. The effector to target cell ratio was significantly higher in the C. butyricum group. In addition, interleukin-6 levels were significantly lower in the C. butyricum group, and inflammation was less severe in this group. The patients undergoing maintenance dialysis with C. butyricum had abundant gut microbiota. They also had a good nutritional status, low systemic inflammation, and a good immunological status.
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Affiliation(s)
- Masateru YAMAMOTO
- Department of Surgery, National Hospital Organization Yanai
Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
- Department of Gastroenterological and Transplant Surgery,
Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi,
Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan
| | - Hiromitsu OHMORI
- Department of Pediatrics, National Hospital Organization
Yanai Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
| | - Daisuke TAKEI
- Department of Surgery, National Hospital Organization Yanai
Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
- Department of Gastroenterological and Transplant Surgery,
Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi,
Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan
| | - Tomio MATSUMOTO
- Department of Surgery, National Hospital Organization Yanai
Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
| | - Masahiko TAKEMOTO
- Department of Surgery, National Hospital Organization Yanai
Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
| | - Masanobu IKEDA
- Department of Surgery, National Hospital Organization Yanai
Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
| | - Ryo SUMIMOTO
- Department of Surgery, National Hospital Organization Yanai
Medical Center, 95 Ihonoshou, Yanai-shi, Yamaguchi 742-1352, Japan
| | - Tsuyoshi KOBAYASHI
- Department of Gastroenterological and Transplant Surgery,
Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi,
Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan
| | - Hideki OHDAN
- Department of Gastroenterological and Transplant Surgery,
Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi,
Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan
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42
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Read E, Curtis MA, Neves JF. The role of oral bacteria in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021; 18:731-742. [PMID: 34400822 DOI: 10.1038/s41575-021-00488-4] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2021] [Indexed: 02/06/2023]
Abstract
Over the past two decades, the importance of the microbiota in health and disease has become evident. Pathological changes to the oral bacterial microbiota, such as those occurring during periodontal disease, are associated with multiple inflammatory conditions, including inflammatory bowel disease. However, the degree to which this association is a consequence of elevated oral inflammation or because oral bacteria can directly drive inflammation at distal sites remains under debate. In this Perspective, we propose that in inflammatory bowel disease, oral disease-associated bacteria translocate to the intestine and directly exacerbate disease. We propose a multistage model that involves pathological changes to the microbial and immune compartments of both the oral cavity and intestine. The evidence to support this hypothesis is critically evaluated and the relevance to other diseases in which oral bacteria have been implicated (including colorectal cancer and liver disease) are discussed.
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Affiliation(s)
- Emily Read
- Centre for Host-Microbiome Interactions, King's College London, London, UK.,Wellcome Trust Cell Therapies and Regenerative Medicine PhD Programme, King's College London, London, UK
| | - Michael A Curtis
- Centre for Host-Microbiome Interactions, King's College London, London, UK
| | - Joana F Neves
- Centre for Host-Microbiome Interactions, King's College London, London, UK.
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43
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Fiocchi C, Dragoni G, Iliopoulos D, Katsanos K, Ramirez VH, Suzuki K, Torres J, Scharl M. Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD-What, Why, and How. J Crohns Colitis 2021; 15:1410-1430. [PMID: 33733656 DOI: 10.1093/ecco-jcc/jjab051] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Many diseases that affect modern humans fall in the category of complex diseases, thus called because they result from a combination of multiple aetiological and pathogenic factors. Regardless of the organ or system affected, complex diseases present major challenges in diagnosis, classification, and management. Current forms of therapy are usually applied in an indiscriminate fashion based on clinical information, but even the most advanced drugs only benefit a limited number of patients and to a variable and unpredictable degree. This 'one measure does not fit all' situation has spurred the notion that therapy for complex disease should be tailored to individual patients or groups of patients, giving rise to the notion of 'precision medicine' [PM]. Inflammatory bowel disease [IBD] is a prototypical complex disease where the need for PM has become increasingly clear. This prompted the European Crohn's and Colitis Organisation to focus the Seventh Scientific Workshop on this emerging theme. The articles in this special issue of the Journal address the various complementary aspects of PM in IBD, including what PM is; why it is needed and how it can be used; how PM can contribute to prediction and prevention of IBD; how IBD PM can aid in prognosis and improve response to therapy; and the challenges and future directions of PM in IBD. This first article of this series is structured on three simple concepts [what, why, and how] and addresses the definition of PM, discusses the rationale for the need of PM in IBD, and outlines the methodology required to implement PM in IBD in a correct and clinically meaningful way.
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Affiliation(s)
- Claudio Fiocchi
- Department of Inflammation & Immunity, Lerner Research Institute, and Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence,Italy.,IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence,Italy
| | | | - Konstantinos Katsanos
- Division of Gastroenterology, Department of Internal Medicine, University of Ioannina School of Health Sciences, Ioannina,Greece
| | - Vicent Hernandez Ramirez
- Department of Gastroenterology, Xerencia Xestión Integrada de Vigo, and Research Group in Digestive Diseases, Galicia Sur Health Research Institute [IIS Galicia Sur], SERGAS-UVIGO, Vigo, Spain
| | - Kohei Suzuki
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX,USA
| | | | - Joana Torres
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
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44
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Tumor Necrosis Factor's Pathway in Crohn's Disease: Potential for Intervention. Int J Mol Sci 2021; 22:ijms221910273. [PMID: 34638616 PMCID: PMC8508644 DOI: 10.3390/ijms221910273] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/18/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022] Open
Abstract
Crohn’s disease (CD) is a chronic disorder characterized by full thickness patchy inflammation of the gastrointestinal tract. The pathogenesis is multifactorial and involves defective innate immune responses, microbiome alterations, and dysregulated activation of the acquired component of mucosal immunity. One of the molecular mediators that is involved at different levels in the initiation and progression of intestinal inflammation characteristic of CD is tumor necrosis factor (TNF). The present manuscript provides a comprehensive review focused on the potential role of TNF in the different phases of CD pathogenesis, particularly in light of its potential clinical implications. Currently available drugs blocking TNF are evaluated and discussed, specifically for open issues that still remain utilizing such therapy. TNF exerts a paramount role in the established phase of intestinal inflammation that characterizes CD patients, and anti-TNF biologics have definitely changed patient management, offering effective and safe options of treatment. Nonetheless, many patients still do not respond to anti-TNF therapy or experience unwanted side-effects. This could partially be due to the role that TNF plays in intestinal homeostasis that is particularly important during the early phase of the inflammatory process. In fact, emerging evidence supporting the dichotomous role of TNF and the identification of molecular markers will guide a more tailored and refined therapy for CD patients in the near future.
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45
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Masu Y, Kanazawa Y, Kakuta Y, Shimoyama Y, Onodera M, Naito T, Moroi R, Kuroha M, Kimura T, Shiga H, Kinouchi Y, Masamune A. Immunoglobulin subtype-coated bacteria are correlated with the disease activity of inflammatory bowel disease. Sci Rep 2021; 11:16672. [PMID: 34404881 PMCID: PMC8371132 DOI: 10.1038/s41598-021-96289-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 08/09/2021] [Indexed: 12/13/2022] Open
Abstract
Immune response involving various immunoglobulin (Ig) isotypes and subtypes to microbiome is involved in the pathogenesis and disease activity of inflammatory bowel diseases (IBDs). To clarify the presence of Ig-coated bacteria in the intestine and its association with disease activity in ulcerative colitis (UC) and Crohn’s disease (CD), we extracted and classified Ig-coated bacteria from fecal samples of 42 patients with IBD and 12 healthy controls (HCs) using flow cytometry and 16S ribosomal RNA sequence analysis. The percentage of bacteria coated with IgA and IgM was higher in patients with IBD than in HCs, and IgG-coated bacteria were found only in patients with IBD. Moreover, the percentages of bacteria coated with IgG1, IgG2, IgG3, and IgM in UC samples and IgG3, IgG4, and IgM in CD samples were correlated with disease activities. The proportions of Bacteroides ovatus and Streptococcus increased during the active phase of CD. Hence, the detailed analysis of Ig-coated bacteria and Ig subtypes using flow cytometry could aid in developing useful indicators of disease activity and identifying more disease-related bacteria, which could become novel treatment targets for IBDs.
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Affiliation(s)
- Yutaro Masu
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Yoshitake Kanazawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.,Department of Gastroenterology, South Miyagi Medical Center, Ogawara, Japan
| | - Yoichi Kakuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
| | - Yusuke Shimoyama
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Motoyuki Onodera
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Takeo Naito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Rintaro Moroi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Masatake Kuroha
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Tomoya Kimura
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Hisashi Shiga
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
| | - Yoshitaka Kinouchi
- Health Administration Center, Center for the Advancement of Higher Education, Tohoku University, Sendai, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan
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46
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Ozaka S, Sonoda A, Ariki S, Kamiyama N, Hidano S, Sachi N, Ito K, Kudo Y, Minata M, Saechue B, Dewayani A, Chalalai T, Soga Y, Takahashi Y, Fukuda C, Mizukami K, Okumura R, Kayama H, Murakami K, Takeda K, Kobayashi T. Protease inhibitory activity of secretory leukocyte protease inhibitor ameliorates murine experimental colitis by protecting the intestinal epithelial barrier. Genes Cells 2021; 26:807-822. [PMID: 34379860 DOI: 10.1111/gtc.12888] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/04/2021] [Accepted: 08/07/2021] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestine, and the dysfunction of intestinal epithelial barrier (IEB) may trigger the onset of IBD. Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that has been implicated in the tissue-protective effect in the skin and lung. We found that SLPI was induced in lipopolysaccharides-treated colon carcinoma cell line and in the colon of dextran sulfate sodium (DSS)-treated mice. SLPI-deficient mice were administered DSS to induce colitis and sustained severe inflammation compared with wild-type mice. The colonic mucosa of SLPI-deficient mice showed more severe inflammation with neutrophil infiltration and higher levels of proinflammatory cytokines compared with control mice. Moreover, neutrophil elastase (NE) activity in SLPI-deficient mice was increased and IEB function was severely impaired in the colon, accompanied with the increased number of apoptotic cells. Importantly, we demonstrated that DSS-induced colitis was ameliorated by administration of protease inhibitor SSR69071 and recombinant SLPI. These results suggest that the protease inhibitory activity of SLPI protects from colitis by preventing IEB dysfunction caused by excessive NE activity, which provides insight into the novel function of SLPI in the regulation of gut homeostasis and therapeutic approaches for IBD.
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Affiliation(s)
- Sotaro Ozaka
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Akira Sonoda
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Shimpei Ariki
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Naganori Kamiyama
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Shinya Hidano
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Nozomi Sachi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kanako Ito
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoko Kudo
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Mizuki Minata
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Benjawan Saechue
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Astri Dewayani
- Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Thanyakorn Chalalai
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yasuhiro Soga
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yuya Takahashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Chiaki Fukuda
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazuhiro Mizukami
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan.,Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Ryu Okumura
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Hisako Kayama
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kiyoshi Takeda
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
| | - Takashi Kobayashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Japan
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47
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Townsend EM, Kelly L, Muscatt G, Box JD, Hargraves N, Lilley D, Jameson E. The Human Gut Phageome: Origins and Roles in the Human Gut Microbiome. Front Cell Infect Microbiol 2021; 11:643214. [PMID: 34150671 PMCID: PMC8213399 DOI: 10.3389/fcimb.2021.643214] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 05/19/2021] [Indexed: 12/14/2022] Open
Abstract
The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.
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Affiliation(s)
- Eleanor M Townsend
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Lucy Kelly
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - George Muscatt
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Joshua D Box
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Nicole Hargraves
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Daniel Lilley
- Warwick Medical School, The University of Warwick, Coventry, United Kingdom
| | - Eleanor Jameson
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
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48
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Aldars-García L, Chaparro M, Gisbert JP. Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease. Microorganisms 2021; 9:microorganisms9050977. [PMID: 33946482 PMCID: PMC8147118 DOI: 10.3390/microorganisms9050977] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.
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Affiliation(s)
- Laila Aldars-García
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - Javier P. Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
- Correspondence: ; Tel.: +34-913-093-911; Fax: +34-915-204-013
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Wang Y, Zou J, Jia Y, Zhang X, Wang C, Shi Y, Guo D, Wu Z, Wang F. The Mechanism of Lavender Essential Oil in the Treatment of Acute Colitis Based on "Quantity-Effect" Weight Coefficient Network Pharmacology. Front Pharmacol 2021; 12:644140. [PMID: 33981227 PMCID: PMC8107818 DOI: 10.3389/fphar.2021.644140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 03/10/2021] [Indexed: 12/30/2022] Open
Abstract
This study aimed to introduce a new weight coefficient combined with network pharmacology to predict the potential active components, action targets, and signal pathways of lavender essential oil and to investigate the therapeutic effect of lavender essential oil on colitis through animal experiments. The component targets of lavender essential oil were mined from the Pubchem and SwissTargetPrediction databases, and the relative content of lavender essential oil was compared with OB (oral bioavailability) to establish a “quantity–effect” weight coefficient. Online databases such as GeneCards and String were used to construct a “lavender essential oil compound target disease target” network to extract the key targets of core compounds acting on diseases. The clusterProfiler package in R language programming of Rstudio software was used to analyze the enrichment of the related targets by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the enriched pathways were reordered according to the “quantity–effect” weight coefficient of the targets they participated in. Following up on the findings, the pharmacodynamic test showed that, after injecting lavender essential oil into mice, the levels of inflammatory cytokines including EGFR, TNF-α, and IFN-γ in serum and colon tissue decreased, and lavender essential oil could mediate Th17 cell differentiation by reducing dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) colonic mucosal damage. The results indicated that lavender essential oil can alleviate DSS-induced colonic mucosal injury in ulcerative Colitis mice. Based on the network pharmacology of the “quantity–effect” weight coefficient, this study indicated that lavender essential oil can regulate the level of inflammatory factors, inhibit inflammatory reactions through a multicomponent and multitarget strategy, and ultimately alleviate the colonic mucosal injury of UC mice. Through the weight coefficient network pharmacology mining, it was concluded that the Th17 cell differentiation, PI3K-Akt signaling pathway, and Th1 and Th2 cell differentiation of lavender essential oil in the treatment of UC may be the key pathway for the treatment of the disease. Through the establishment of a weight coefficient combined with network pharmacology and the combination of dose and effect, it shows that network pharmacology may provide a better basis for the treatment of disease mechanism.
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Affiliation(s)
- Yao Wang
- Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Junbo Zou
- Department of Pharmaceutics, College of Pharmacy, the Key Laboratory of Basic and New Drug Resea Rchof Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Yanzhuo Jia
- Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Xiaofei Zhang
- Department of Pharmaceutics, College of Pharmacy, the Key Laboratory of Basic and New Drug Resea Rchof Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Changli Wang
- Department of Pharmaceutics, College of Pharmacy, the Key Laboratory of Basic and New Drug Resea Rchof Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Yajun Shi
- Department of Pharmaceutics, College of Pharmacy, the Key Laboratory of Basic and New Drug Resea Rchof Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Dongyan Guo
- Department of Pharmaceutics, College of Pharmacy, the Key Laboratory of Basic and New Drug Resea Rchof Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Zhenfeng Wu
- Department of Pharmaceutics, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Fang Wang
- Department of Pharmaceutics, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
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Kobayashi R, Hashizume-Takizawa T, Kurita-Ochiai T. Lactic acid bacteria prevent both periodontitis and atherosclerosis exacerbated by periodontitis in spontaneously hyperlipidemic mice. J Periodontal Res 2021; 56:753-760. [PMID: 33729588 DOI: 10.1111/jre.12874] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 02/01/2021] [Accepted: 02/21/2021] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND OBJECTIVE Recent studies have shown a link between periodontal disease and cardiovascular disease. We have previously reported that oral administration of Porphyromonas gingivalis (Pg) accelerates atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoeshl ) mice. This study evaluated the potential of lactic acid bacteria (LAB) to change the intestinal flora changes induced by periodontopathic bacteria and to prevent/slow down the development of atherosclerosis. METHODS Lactobacillus gasseri O3-2 (Lg) was orally intubated in Apoeshl mice for 5 weeks. Three weeks after oral intubation, the mice were orally infected with Pg for 2 weeks. RESULTS Thirty days after the last infection with Pg, Lg+Pg-treated mice showed a significant reduction in alveolar bone loss compared to the Pg-treated group. The Lg treatment restored the Pg-induced intestinal flora disturbance to normal. Furthermore, a significant decrease in atherosclerotic plaque lesion size and suppressed inflammatory cytokine production in the aorta were detected in the Lg + Pg-treated group. In contrast, blood concentrations of TMAO, histidine, and carnitine were enhanced by the Lg treatment but decreased by Lg + Pg treatment. CONCLUSION These results suggest that oral Lg treatment is effective in preventing periodontitis and atherosclerosis.
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Affiliation(s)
- Ryoki Kobayashi
- Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Tomomi Hashizume-Takizawa
- Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Tomoko Kurita-Ochiai
- Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
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