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Guo Z, He L, Wang W, Tian S, Lin R. FUT2-dependent fucosylation of LAMP1 promotes the apoptosis of colorectal cancer cells by regulating the autophagy-lysosomal pathway. Cancer Lett 2025; 619:217643. [PMID: 40112906 DOI: 10.1016/j.canlet.2025.217643] [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: 12/23/2024] [Revised: 03/06/2025] [Accepted: 03/15/2025] [Indexed: 03/22/2025]
Abstract
Fucosyltransferase 2 (FUT2) is an enzyme that adds fucose to proteins or lipids via α-1,2-fucosylation in the intestinal mucosa. While FUT2 deficiency is linked to increased susceptibility to inflammatory bowel disease (IBD), its role in colorectal cancer (CRC) is unclear, and the molecular mechanisms involved remain largely unknown. We established an azoxymethane (AOM) and dextran sulfate sodium (DSS) model to induce CRC. FUT2 expression was assessed in human CRC tissues, AOM/DSS-induced mouse models, and CRC cell lines using qRT-PCR, western blotting, and UEA-I staining. FUT2 knockout (FUT2△IEC) mice were treated with AOM/DSS, and FUT2-overexpressing CRC cells were created to evaluate the effects of FUT2 on apoptosis in both in vitro and in vivo settings through Western blot analyses and functional assays. N-glycoproteomics, UEA-I chromatography, and co-immunoprecipitation were utilized to identify regulatory mechanisms and target fucosylated proteins. FUT2 expression and α-1,2-fucosylation were significantly decreased in CRC. FUT2 deficiency worsened AOM/DSS-induced CRC and reduced tumor apoptosis, while FUT2 overexpression induced apoptosis and inhibited proliferation in CRC cells and xenografts. Mechanistically, FUT2 appears to suppress autophagy by impairing lysosomal function and directly targeting and fucosylating LAMP1, contributing to lysosomal dysfunction. Our study reveals a fucosylation-dependent antitumor mechanism of FUT2 in CRC, suggesting potential therapeutic strategies for CRC treatment.
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Affiliation(s)
- Zijun Guo
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Lingnan He
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai, China
| | - Weijun Wang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuxin Tian
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong Lin
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Cheng H, Li H, Li Z, Wang Y, Liu L, Wang J, Ma X, Tan B. The role of glycosylated mucins in maintaining intestinal homeostasis and gut health. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2025; 21:439-446. [PMID: 40491555 PMCID: PMC12148640 DOI: 10.1016/j.aninu.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 01/12/2025] [Accepted: 03/12/2025] [Indexed: 06/11/2025]
Abstract
The intestinal mucus barrier is a crucial component of the host's innate defense system, playing a vital role in regulating intestinal microecology and maintaining intestinal homeostasis. Glycosylated mucins, the core components of this barrier, are essential for preserving its integrity by preventing bacterial degradation. Additionally, mucins significantly contribute to establishing a balanced symbiotic relationship between the host and microbes. These mucins have the potential to mitigate intestinal epithelial damage by capturing and transporting cell debris and pathogenic bacteria. Meanwhile, certain bacteria help maintain the equilibrium and stability of the gut microbiome by degrading glycosylated mucins to utilize the carbohydrate chains, thus affecting the cytokine expression to regulate the synthesis and secretion of specific glycans. Investigating the complex connections between the mucus barrier and mucin glycosylation holds great promise for advancing our understanding of gastrointestinal disease mechanisms, paving the way for innovative prevention and treatment strategies.
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Affiliation(s)
- Hao Cheng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Hunan University of Arts and Science, Changde 415000, China
- Yuelushan Laboratory, Changsha 410128, China
| | - Hao Li
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Hunan University of Arts and Science, Changde 415000, China
- Yuelushan Laboratory, Changsha 410128, China
| | - Zhong Li
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Yuelushan Laboratory, Changsha 410128, China
| | - Yun Wang
- Hunan University of Arts and Science, Changde 415000, China
| | - Liangguo Liu
- Hunan University of Arts and Science, Changde 415000, China
| | - Jing Wang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Yuelushan Laboratory, Changsha 410128, China
| | - Xiaokang Ma
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Yuelushan Laboratory, Changsha 410128, China
| | - Bie Tan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Yuelushan Laboratory, Changsha 410128, China
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Strojny Z, Kawka E, Strojny M, Kucz-Chrostowska A, Żuraszek-Szymańska J, Sikora W, Deja T, Konopka M, Sato M, Wakamura T, Negoro H, Surdacka A, Korybalska K, Bręborowicz A, Witowski J, Kanikowska D. Exploring the impact of chronotype, chrononutrition and lifestyle on bladder cancer. Int Urol Nephrol 2025:10.1007/s11255-025-04371-y. [PMID: 39982656 DOI: 10.1007/s11255-025-04371-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 01/07/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND The misalignment of sleep and eating patterns with biological cycles is a significant issue that could have detrimental effects on health and is prevalent among cancer patients. Sleep duration, chronotype, and nutrition may be linked to the presence of urothelial tract cancer. Bladder cancer is the most frequently diagnosed cancer in the urinary system. The study estimated bladder cancer patients' nutrition behavior, sleep preferences, and chronotype. METHODS 101 patients were enrolled. Based on histopathological examination, they were divided into the cancer group (n = 69) and the non-cancer group (n = 32). Lifestyle was assessed through three questionnaires about sleep, chronotype patterns, and chrononutrition behaviors: social jet lag, eating jet lag, eating window, evening and morning latency. The analysis was also completed by assessing salivary alpha-amylase and immunoglobulin A (IgA). RESULTS In cancer and non-cancer patients, we did not find differences between the chronotypes (p = 0.0634) or other measured factors. Most of the studied population did not present social or eating jet lag and morning or evening latency. In addition, the total sleep duration in these groups was similar 8.5 (5.0-13.0) vs 9.0 (5.0-11.5) hours per day (p > 0.99). The eating window did not differ between the groups (p = 0.061). Furthermore, the assessment of salivary alpha-amylase 193.9 U/ml (10.2-1173.0) and IgA 129.0 μg/ml (5.1-801.1) (p = 0.43; p = 0.18, respectively) showed no differences. CONCLUSIONS In this preliminary study, we did not observe a domination of particular types of chronotypes in the cancer and non-cancer groups. Moreover, there were no significant changes in lifestyle and chrononutrition behavior, except weak difference between groups in eating window. However, it provides a robust foundation for further research and clinical applications.
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Affiliation(s)
- Zofia Strojny
- Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, Bukowska 70, 60-812, Poznan, Poland.
| | - Edyta Kawka
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Marcin Strojny
- Department of Urology with the Sub-Department of Oncological Urology, Hospital of the Ministry of Internal Affairs and Administration, Poznan, Poland
| | | | | | - Wiesław Sikora
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Tomasz Deja
- Department of Urology with the Sub-Department of Oncological Urology, Hospital of the Ministry of Internal Affairs and Administration, Poznan, Poland
| | - Maciej Konopka
- Department of Urology with the Sub-Department of Oncological Urology, Hospital of the Ministry of Internal Affairs and Administration, Poznan, Poland
| | - Maki Sato
- Institutional Research, Aichi Medical University School of Medicine, Aichi, Japan
| | - Tomoko Wakamura
- Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiromitsu Negoro
- Department of Urology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Anna Surdacka
- Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, Bukowska 70, 60-812, Poznan, Poland
| | - Katarzyna Korybalska
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Andrzej Bręborowicz
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
- Collegium Medicum, University of Zielona Góra, Zielona Góra, Poland
| | - Janusz Witowski
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Dominika Kanikowska
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
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Lee J, Oh SJ, Ha E, Shin GY, Kim HJ, Kim K, Lee CK. Gut microbial and human genetic signatures of inflammatory bowel disease increase risk of comorbid mental disorders. NPJ Genom Med 2024; 9:52. [PMID: 39472439 PMCID: PMC11522461 DOI: 10.1038/s41525-024-00440-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 09/25/2024] [Indexed: 11/02/2024] Open
Abstract
The high prevalence of comorbid mental disorders (CMDs) in patients with inflammatory bowel disease (IBD) is well-documented. This study delves into the intricate CMD-IBD relationship through comprehensive analyses using human variants, gut microbiome, and anxiety/depression estimates from a cohort of 507 IBD patients and 75 controls. Notably, patients with IBD, especially those with CMD, exhibited lower diversity than controls. We identified 106 differentially abundant taxa (DATs) in IBD patients compared to controls and 21 DATs distinguishing CMD-affected from CMD-free IBD patients. Microbial IBD-risk scores, reflecting an individual's microbial burden for IBD, revealed a significant enrichment of IBD-risk signatures in CMD-affected patients compared to CMD-free patients. Additionally, there was an IBD-risk variant potentially regulating the abundance of an IBD/CMD-associated DAT, suggesting an interplay between IBD-risk variants and dysbiosis in CMD. Our investigation underscores the pivotal role of IBD-associated gut dysbiosis in predisposing IBD patients to CMD, partially through genetic variant-mediated mechanisms.
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Affiliation(s)
- Junho Lee
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea
| | - Shin Ju Oh
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Eunji Ha
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea
| | - Ga Young Shin
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Hyo Jong Kim
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Kwangwoo Kim
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
| | - Chang Kyun Lee
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
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Nishiyama NC, Silverstein S, Darlington K, Kennedy Ng MM, Clough KM, Bauer M, Beasley C, Bharadwaj A, Ganesan R, Kapadia MR, Lau G, Lian G, Rahbar R, Sadiq TS, Schaner MR, Stem J, Friton J, Faubion WA, Sheikh SZ, Furey TS. eQTL in diseased colon tissue identifies novel target genes associated with IBD. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.14.618229. [PMID: 39464142 PMCID: PMC11507739 DOI: 10.1101/2024.10.14.618229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci. eQTL in IBD tissue were enriched for IBD GWAS loci colocalizations, provided novel evidence for IBD-associated genes such as ABO and TNFRSF14, and identified additional target genes compared to non-IBD tissue eQTL. IBD-associated eQTL unique to diseased tissue had distinct regulatory and functional characteristics with increased effect sizes. Together, these highlight the importance of eQTL studies in diseased tissue for understanding functional consequences of genetic variants, and elucidating molecular mechanisms and regulation of key genes involved in IBD.
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Affiliation(s)
- Nina C. Nishiyama
- Curriculum in Bioinformatics and Computational Biology, Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Sophie Silverstein
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Kimberly Darlington
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Meaghan M. Kennedy Ng
- Curriculum in Bioinformatics and Computational Biology, Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Katelyn M. Clough
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Curriculum in Toxicology and Environmental Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Mikaela Bauer
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Caroline Beasley
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Akshatha Bharadwaj
- Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Rajee Ganesan
- Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Muneera R. Kapadia
- Department of Surgery, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Gwen Lau
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Grace Lian
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Reza Rahbar
- Department of Surgery, REX Healthcare of Wakefield, Raleigh, North Carolina, USA
| | - Timothy S. Sadiq
- Department of Surgery, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Matthew R. Schaner
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jonathan Stem
- Department of Surgery, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jessica Friton
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - William A. Faubion
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Shehzad Z. Sheikh
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Curriculum in Toxicology and Environmental Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Terrence S. Furey
- Curriculum in Bioinformatics and Computational Biology, Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Cao R, Gao T, Yue J, Sun G, Yang X. Disordered Gut Microbiome and Alterations in Metabolic Patterns Are Associated With Hypertensive Left Ventricular Hypertrophy. J Am Heart Assoc 2024; 13:e034230. [PMID: 39342506 DOI: 10.1161/jaha.123.034230] [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: 12/29/2023] [Accepted: 08/23/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Left ventricular hypertrophy (LVH) is most common when driven by hypertension, and it is a strong independent risk factor for adverse cardiovascular events and death. Some animal models support a role for gut microbiota and metabolites in the development of LVH, but cohort studies confirming these findings in populations are lacking. METHODS AND RESULTS We investigated the alterations of gut microbiota and metabolites in 30 patients with hypertension, 30 patients with hypertensive LVH, and 30 matched controls on the basis of 16S rDNA and metabolomic analyses. Thirty stool and 90 serum samples were collected in fasting conditions. ANOVA/Kruskal-Wallis/Pearson's χ2/Fisher's exact test and Bonferroni's correction were used (P<0.0167) for comparison among the 3 groups. A regression analysis and subgroup analysis were performed between gut microbiota and left ventricular mass index (LVMI) and metabolites and LVMI, respectively. Spearman correlation analysis was performed between metabolites and flora and metabolites and LVMI. We observed LVH-enriched Faecalitalea (β=6758.55 [95% CI, 2080.92-11436.18]; P=0.009), Turicibacter (β=8424.76 [95% CI, 2494.05-14355.47]; P=0.01), Ruminococcus torques group (β=840.88 [95% CI, 223.1-1458.67]; P=0.013), and Erysipelotrichaceae UCG-003 (β=856.37 [95% CI, 182.76-1529.98]; P=0.019) were positively correlated with LVMI. A total of 1141 (in sera) and 2657 (in feces) metabolites were identified. There was a sex-specific association between metabolites and LVMI. Significant changes in metabolic pathways in LVH were also observed, especially bile acid and lipid metabolism pathways. CONCLUSIONS Our study demonstrated the disordered gut microbiota and microbial metabolite profiles in LVH. This highlights the roles of gut bacteria and metabolite in this disease and could lead to new intervention, diagnostic, or management paradigms for LVH. REGISTRATION URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR2200055603.
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Affiliation(s)
- Rong Cao
- Department of Cardiovascular Medicine Research Institute of Hypertension, The Second Affiliated Hospital of Baotou Medical College Baotou Inner Mongolia China
- Department of Cardiovascular Medicine The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian China
| | - Ting Gao
- Geriatric Department Baotou Central Hospital Baotou Inner Mongolia China
| | - Jianwei Yue
- Department of Cardiovascular Medicine Research Institute of Hypertension, The Second Affiliated Hospital of Baotou Medical College Baotou Inner Mongolia China
| | - Gang Sun
- Department of Cardiovascular Medicine Research Institute of Hypertension, The Second Affiliated Hospital of Baotou Medical College Baotou Inner Mongolia China
| | - Xiaomin Yang
- General Medicine Sir Run Run Shaw Hospital, Zhejiang University Zhejiang China
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7
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Yuan W, Luo Q, Wu N. Investigating the shared genetic basis of inflammatory bowel disease and systemic lupus erythematosus using genetic overlap analysis. BMC Genomics 2024; 25:868. [PMID: 39285290 PMCID: PMC11406968 DOI: 10.1186/s12864-024-10787-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 09/09/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) are autoimmune diseases that often coexist clinically. This phenomenon might be due to shared genetic components. METHODS Genome-wide association study (GWAS) data for IBD and SLE were analyzed to determine both global and local genetic correlations using three methodologies: linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA. The genetic overlap and risk loci were subsequently examined using the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework. Furthermore, a multi-trait analysis of MTAG was employed to validate the loci, followed by an LDSC analysis focusing on tissue-specific gene expression. RESULTS GWAS findings demonstrated a marked global genetic correlation between IBD (including Crohn's disease and ulcerative colitis) and SLE. Locally, SLE showed a strong association with IBD and Crohn's disease on chromosomes 10, 19, and 22. ConjFDR analysis confirmed the genetic overlap and identified relevant genetic risk loci. MTAG further validated several shared susceptibility genes. Additionally, the LDSC-SEG analysis results indicate that IBD (including CD and UC) and SLE are jointly enriched in the tissues of Spleen and Whole Blood. CONCLUSION This study confirms a genetic overlap between IBD and SLE, identifying marked comorbid genes and offering new insights for treating these diseases.
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Affiliation(s)
- Weichao Yuan
- Department of Anorectal Surgery, Affiliated Hospital of Jiujiang University, Jiujiang, China
| | - Qinghua Luo
- Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Na Wu
- Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, China.
- Department of Gastroenterology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China.
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8
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Zakerska-Banaszak O, Zuraszek-Szymanska J, Eder P, Ladziak K, Slomski R, Skrzypczak-Zielinska M. The Role of Host Genetics and Intestinal Microbiota and Metabolome as a New Insight into IBD Pathogenesis. Int J Mol Sci 2024; 25:9589. [PMID: 39273536 PMCID: PMC11394875 DOI: 10.3390/ijms25179589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024] Open
Abstract
Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract whose incidence increases every year. Scientific research constantly delivers new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies have unanimously confirmed the association of gut microbial dysbiosis with IBD and its contribution to the regulation of the inflammatory process. It transpires that the altered composition of pathogenic and commensal bacteria is not only characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. The crucial function of the microbial metabolome in the human body is altered, which causes a wide range of effects on the host, thus providing a basis for the disease. On the other hand, human genomic and functional research has revealed more loci that play an essential role in gut homeostasis regulation, the immune response, and intestinal epithelial function. This review aims to organize and summarize the currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, notably, host genetic composition, intestinal microbiota and metabolome, and immune regulation.
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Affiliation(s)
| | | | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Karolina Ladziak
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
| | - Ryszard Slomski
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
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9
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Minea H, Singeap AM, Minea M, Juncu S, Muzica C, Sfarti CV, Girleanu I, Chiriac S, Miftode ID, Stanciu C, Trifan A. The Contribution of Genetic and Epigenetic Factors: An Emerging Concept in the Assessment and Prognosis of Inflammatory Bowel Diseases. Int J Mol Sci 2024; 25:8420. [PMID: 39125988 PMCID: PMC11313574 DOI: 10.3390/ijms25158420] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/25/2024] [Accepted: 07/27/2024] [Indexed: 08/12/2024] Open
Abstract
Inflammatory bowel disease (IBD) represents heterogeneous and relapsing intestinal conditions with a severe impact on the quality of life of individuals and a continuously increasing prevalence. In recent years, the development of sequencing technology has provided new means of exploring the complex pathogenesis of IBD. An ideal solution is represented by the approach of precision medicine that investigates multiple cellular and molecular interactions, which are tools that perform a holistic, systematic, and impartial analysis of the genomic, transcriptomic, proteomic, metabolomic, and microbiomics sets. Hence, it has led to the orientation of current research towards the identification of new biomarkers that could be successfully used in the management of IBD patients. Multi-omics explores the dimension of variation in the characteristics of these diseases, offering the advantage of understanding the cellular and molecular mechanisms that affect intestinal homeostasis for a much better prediction of disease development and choice of treatment. This review focuses on the progress made in the field of prognostic and predictive biomarkers, highlighting the limitations, challenges, and also the opportunities associated with the application of genomics and epigenomics technologies in clinical practice.
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Affiliation(s)
- Horia Minea
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Manuela Minea
- Department of Microbiology, The National Institute of Public Health, 700464 Iasi, Romania;
| | - Simona Juncu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Catalin Victor Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ioana Diandra Miftode
- Department of Radiology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania;
- Department of Radiology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (S.J.); (C.V.S.); (I.G.); (S.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
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Chen W, Li Y, Wang W, Gao S, Hu J, Xiang B, Wu D, Jiao N, Xu T, Zhi M, Zhu L, Zhu R. Enhanced microbiota profiling in patients with quiescent Crohn's disease through comparison with paired healthy first-degree relatives. Cell Rep Med 2024; 5:101624. [PMID: 38942021 PMCID: PMC11293350 DOI: 10.1016/j.xcrm.2024.101624] [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: 11/04/2023] [Revised: 04/09/2024] [Accepted: 06/07/2024] [Indexed: 06/30/2024]
Abstract
Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.
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Affiliation(s)
- Wanning Chen
- Department of Gastroenterology, the Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, P.R. China
| | - Yichen Li
- Medical College, Jiaying University, Meizhou 514031, P. R. China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P.R. China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology; Biomedical Innovation Center; The Sixth Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, P.R. China
| | - Wenxia Wang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology; Biomedical Innovation Center; The Sixth Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, P.R. China
| | - Sheng Gao
- Department of Gastroenterology, the Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, P.R. China
| | - Jun Hu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology; Biomedical Innovation Center; The Sixth Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, P.R. China; Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China
| | - Bingjie Xiang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology; Biomedical Innovation Center; The Sixth Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, P.R. China; Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China
| | - Dingfeng Wu
- Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310058, Zhejiang, P.R. China
| | - Na Jiao
- Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310058, Zhejiang, P.R. China
| | - Tao Xu
- Medical College, Jiaying University, Meizhou 514031, P. R. China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P.R. China
| | - Min Zhi
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology; Biomedical Innovation Center; The Sixth Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, P.R. China; Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China.
| | - Lixin Zhu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology; Biomedical Innovation Center; The Sixth Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, P.R. China.
| | - Ruixin Zhu
- Department of Gastroenterology, the Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, P.R. China.
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Chen Y, Ye S, Shi J, Wang H, Deng G, Wang G, Wang S, Yuan Q, Yang L, Mou T. Functional evaluation of pure natural edible Ferment: protective function on ulcerative colitis. Front Microbiol 2024; 15:1367630. [PMID: 38952444 PMCID: PMC11215050 DOI: 10.3389/fmicb.2024.1367630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/31/2024] [Indexed: 07/03/2024] Open
Abstract
Purpose To investigate the therapeutic efficiency of a novel drink termed "Ferment" in cases of ulcerative colitis (UC) and its influence on the gut microbiota. Method In this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing. Result After Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced. Conclusion These data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.
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Affiliation(s)
- Yanjun Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shengzhi Ye
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiaolong Shi
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hao Wang
- First Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Guangxu Deng
- Department of Gastrointestinal and Anorectal, The First People’s Hospital of Zhaoqing, Zhaoqing, China
| | | | - Shijie Wang
- College of Foods Science and Biology, Hebei University of Science and Technology, Shijiazhuang, China
- Junlebao Dairy Group Co., Ltd., Shijiazhuang, China
| | - Qingbin Yuan
- Junlebao Dairy Group Co., Ltd., Shijiazhuang, China
| | - Lunan Yang
- Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Tingyu Mou
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, China
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12
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Li N, Oh JH, Suh JH, Jin SP, Lee DH, Lee Y, Chung JH. Impact of fucosyltransferase 1-mediated epidermal blood group antigen H on anti-inflammatory response in atopic dermatitis. Front Immunol 2024; 15:1365430. [PMID: 38840912 PMCID: PMC11151169 DOI: 10.3389/fimmu.2024.1365430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 05/07/2024] [Indexed: 06/07/2024] Open
Abstract
The presence of the blood group H2 antigen on the membrane of red blood cells determines blood type O in individuals and this H2 antigen serves as a precursor to the A and B antigens expressed in blood types A and B, respectively. However, the specific involvement of ABH antigens in skin diseases is unknown. Therefore, we aim to investigate the expression of ABH antigens in skin tissue of patients with atopic dermatitis (AD) and MC903-induced AD-like mice. We demonstrated that the expression of ABH antigen is primarily located in the granular and horny layers of the skin in healthy control individuals. However, in patients with AD, the expression of the ABH antigen was absent or diminished in these layers, while the H2 antigen expression increased in the spinous layers of the affected skin lesions. Then, we investigated the biological function of blood group H antigen mediated by fucosyltransferase 1 (Fut1) in the skin, utilizing an AD mouse model induced by MC903 in wild-type (WT) and Fut1-knockout mice. After the application of MC903, Fut1-deficient mice, with no H2 antigen expression on their skin, exhibited more severe clinical signs, increased ear swelling, and elevated serum IgE levels compared with those of WT mice. Additionally, the MC903-induced thickening of both the epidermis and dermis was more pronounced in Fut1-deficient mice than that in WT mice. Furthermore, Fut1-deficient mice showed a significantly higher production of interleukin-4 (IL-4) and IL-6 in skin lesions compared with that of their WT counterparts. The expression of chemokines, particularly Ccl2 and Ccl8, was notably higher in Fut1-deficient mice compared with those of WT mice. The infiltration of CD4+ T cells, eosinophils, and mast cells into the lesional skin was significantly elevated in Fut1-deficient mice compared with that in WT mice. These findings demonstrate the protective role of H2 antigen expression against AD-like inflammation and highlight its potential therapeutic impact on AD through the regulation of blood group antigens.
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Affiliation(s)
- Na Li
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Jang-Hee Oh
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joong Heon Suh
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Seon-Pil Jin
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Dong Hun Lee
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Youngae Lee
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jin Ho Chung
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
- Institute on Aging, Seoul National University, Seoul, Republic of Korea
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13
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Luo D, Yan L, Wang Z, Ji X, Pei N, Jia J, Luo Y, Ouyang H, Yang S, Feng Y. Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites. Appl Microbiol Biotechnol 2024; 108:292. [PMID: 38592514 PMCID: PMC11003895 DOI: 10.1007/s00253-024-13099-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/23/2024] [Accepted: 02/28/2024] [Indexed: 04/10/2024]
Abstract
Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.
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Affiliation(s)
- Dewei Luo
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China
| | - Li Yan
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China
| | - Zhujun Wang
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China
| | - Xiaofan Ji
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China
| | - Na Pei
- Xinyu University, No. 2666 Yangguang Road, Xinyu, 338004, People's Republic of China
| | - Jing Jia
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China
| | - Yingying Luo
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China.
| | - Hui Ouyang
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China.
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 338004, People's Republic of China.
| | - Shilin Yang
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China
| | - Yulin Feng
- Jiangxi University of Traditional Chinese Medicine, No. 818 Yunwan Road, Nanchang, 330002, People's Republic of China.
- National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, No. 56 Yangming Road, Nanchang, 330006, People's Republic of China.
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Zhao T, Zhang Y, Nan L, Zhu Q, Wang S, Xie Y, Dong X, Cao C, Lin X, Lu Y, Liu Y, Huang L, Gong G, Wang Z. Impact of structurally diverse polysaccharides on colonic mucin O-glycosylation and gut microbiota. NPJ Biofilms Microbiomes 2023; 9:97. [PMID: 38081891 PMCID: PMC10713555 DOI: 10.1038/s41522-023-00468-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of the colonic mucosa and gut microbiome were investigated in C57BL/6J mice fed six structurally diverse dietary polysaccharides and a mixture of six fibers. Dietary polysaccharides increased total O-glycans, mainly by stimulating neutral glycans. Highly branched arabinogalactan promoted terminally fucosylated core 1 O-glycans; whereas linear polysaccharides, including pectin, konjac glucomannan, inulin, and the fiber mixture, favored terminally di-fucosylated O-glycans. The last three polysaccharides also lowered the level of sulfated O-glycans and sialylated mono-fucosylated O-glycans. Varied monosaccharide composition in mixed polysaccharides had a synergistic beneficial effect, boosting fucosylated neutral glycans, decreasing acidic glycans, and stimulating microbial richness and diversity. Dietary polysaccharides containing arabinose and sulfate groups enhanced the relative abundances of Akkermansia and Muribaculaceae, respectively. The present comparison reveals the relationship between dietary polysaccharide structure, mucin O-glycan composition, and intestinal microorganisms.
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Affiliation(s)
- Tong Zhao
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Yue Zhang
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Linhua Nan
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Qing Zhu
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Shukai Wang
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Yutao Xie
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Xinling Dong
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Cui Cao
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Xiaoliang Lin
- Infinitus (China) Company Ltd, Guangzhou, 510000, Guangdong, China
| | - Yu Lu
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Yuxia Liu
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Linjuan Huang
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China
| | - Guiping Gong
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China.
| | - Zhongfu Wang
- Shaanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, 710069, China.
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15
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Widjaja F, Rietjens IMCM. From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes. Biomedicines 2023; 11:2658. [PMID: 37893032 PMCID: PMC10603957 DOI: 10.3390/biomedicines11102658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/22/2023] [Accepted: 09/24/2023] [Indexed: 10/29/2023] Open
Abstract
The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine-feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either -20 °C for up to a few months or -80 °C for a longer period-up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.
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Affiliation(s)
- Frances Widjaja
- Division of Toxicology, Wageningen University & Research, 6708 WE Wageningen, The Netherlands;
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16
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Mammadov RA, Selten JW, Roest HP, Verhoeven CJ, Maroni L, Bril SI, Tolenaars D, Gadjradj PS, van de Graaf SFJ, Oude Elferink RPJ, Kwekkeboom J, Metselaar HJ, Peppelenbosch MP, Beuers U, IJzermans JNM, van der Laan LJW. Intestinal Bacteremia After Liver Transplantation Is a Risk Factor for Recurrence of Primary Sclerosing Cholangitis. Transplantation 2023; 107:1764-1775. [PMID: 36978227 DOI: 10.1097/tp.0000000000004563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic progressive pathological process, related to inflammatory bowel disease and subsequent bacterial translocation. Liver transplantation (LT) is the only curative therapy, but outcomes are compromised by recurrence of PSC (rPSC). The aim of the study was to investigate a potential link between intestinal bacteremia, fucosyltransferase-2 (FUT2), and rPSC after LT. METHODS LT recipients with PSC (n = 81) or without PSC (n = 271) were analyzed for clinical outcomes and positive bacterial blood cultures. A link between bacteremia and the genetic variant of the FUT2 gene was investigated. RESULTS The incidence of inflammatory bowel disease was significantly higher in PSC recipients but not associated with rPSC. Bacteremia occurred in 31% of PSC recipients. The incidence of rPSC was 37% and was significantly more common in patients with intestinal bacteremia versus no bacteremia (82% versus 30%; P = 0.003). The nonsecretor polymorphism of the FUT2 gene was identified as a genetic risk factor for both intestinal bacteremia and rPSC. Combined FUT2 genotype and intestinal bacteremia in recipients resulted in the highest risk for rPSC (hazard ratio, 15.3; P < 0.001). CONCLUSIONS Thus, in this article, we showed that bacterial translocation is associated with rPSC after LT and related to the FUT2 nonsecretor status.
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Affiliation(s)
- Ruslan A Mammadov
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands
| | - Jasmijn W Selten
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
| | - Henk P Roest
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
| | - Cornelia J Verhoeven
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
- Department of Otorhinolaryngology, University Medical Center Groningen, The Netherlands
| | - Luca Maroni
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
- Department of Gastroenterology, Marche Polytechnic University, Ancona, Italy
| | - Sandra I Bril
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
| | - Dagmar Tolenaars
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
| | - Pravesh S Gadjradj
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
| | - Stan F J van de Graaf
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
| | - Ronald P J Oude Elferink
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
| | - Jaap Kwekkeboom
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands
| | - Ulrich Beuers
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
| | - Luc J W van der Laan
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands
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17
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Attia H, ElBanna SA, Khattab RA, Farag MA, Yassin AS, Aziz RK. Integrating Microbiome Analysis, Metabolomics, Bioinformatics, and Histopathology to Elucidate the Protective Effects of Pomegranate Juice against Benzo-alpha-pyrene-Induced Colon Pathologies. Int J Mol Sci 2023; 24:10691. [PMID: 37445869 DOI: 10.3390/ijms241310691] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/19/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Polycyclic aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are common dietary pollutants with potential carcinogenic activity, while polyphenols are potential chemopreventive antioxidants. Although several health benefits are attributed to polyphenol-rich pomegranate, little is known about its interaction with BaP. This study integrates histochemical, microbiomic, and metabolomic approaches to investigate the protective effects of pomegranate juice from BaP-induced pathologies. To this end, 48 Sprague-Dawley rats received, for four weeks, either pomegranate, BaP, both, or neither (n = 12 rats per group). Whereas histochemical examination of the colon indicated tissue damage marked by mucin depletion in BaP-fed animals, which was partially restored by administration of pomegranate juice, the fecal microbiome and metabolome retained their resilience, except for key changes related to pomegranate and BaP biotransformation. Meanwhile, dramatic microbiome restructuring and metabolome shift were observed as a consequence of the elapsed time (age factor). Additionally, the analysis allowed a thorough examination of fecal microbiome-metabolome associations, which delineated six microbiome clusters (marked by a differential abundance of Lactobacillaceae and Prevotellaceae, Rumincococcaceae, and Erysipelotrichaceae) and two major metabolome clusters (a sugar- and amino-acids-dominated metabotype vs. a cluster of fatty acids and hydrocarbons), with sugar alcohols maintaining a unique signature. In conclusion, using paired comparisons to minimize inter-individual animal variations allowed the dissection of temporal vs. treatment-derived variations. Microbiome-metabolome association clusters may be further exploited for metabotype prediction and gut-health biomarker discovery.
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Affiliation(s)
- Heba Attia
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Shahira A ElBanna
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Rania A Khattab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Mohamed A Farag
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Aymen S Yassin
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Ramy K Aziz
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Microbiology and Immunology Research Program, Children's Cancer Hospital Egypt 57357, Cairo 11617, Egypt
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18
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Wu D, Zhang Z, Shao K, Wang X, Huang F, Qi J, Duan Y, Jia Y, Xu M. Effects of Sodium Butyrate Supplementation in Milk on the Growth Performance and Intestinal Microbiota of Preweaning Holstein Calves. Animals (Basel) 2023; 13:2069. [PMID: 37443869 DOI: 10.3390/ani13132069] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 06/10/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The aim of the present study was to investigate the effects of sodium butyrate (SB) supplementation on the growth and intestinal microbiota of preweaning dairy calves. Eighty newborn Holstein calves (56 female and 24 male) were randomly allocated to four treatment groups with 20 calves each (14 female and 6 male). The suckling milk for the four treatments was supplemented with 0, 4.4, 8.8, or 17.6 g/d SB. During the 6-week experiment, dry matter intake was recorded daily, body weight was measured weekly, and rectal fecal samples were collected in the 2nd week. The V3-V4 hypervariable regions of the microbial 16S rRNA were amplified and then sequenced. SB supplementation elevated average daily gains (ADGs) in the first and second weeks. The optimal SB supplementation level for the whole preweaning period was 8.78 g/d, as revealed by analyzing the whole preweaning period ADG using second-order polynomial regression (quadratic) equations. The alpha diversity (Shannon diversity index), beta diversity, core phyla and genera, and function of the intestinal microbiota were affected by SB supplementation. In addition, the Shannon diversity index and core phyla and genera of the intestinal microbiota were correlated with calf growth-related indices. Overall, SB supplementation in suckling milk improved the growth performance and intestinal microbiota development of dairy calves in a quadratic manner, and regression analysis indicated an optimal supplementation level of 8.78 g/d.
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Affiliation(s)
- Donglin Wu
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Zhanhe Zhang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Kai Shao
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Xing Wang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Fudong Huang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Jingwei Qi
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
- Inner Mongolia Herbivorous Livestock Feed Engineering and Technology Research Center, Hohhot 010018, China
| | - Yizong Duan
- Shazhou Dairy Co., Ltd., Ulanqab 013750, China
| | - Yang Jia
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Ming Xu
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
- Inner Mongolia Herbivorous Livestock Feed Engineering and Technology Research Center, Hohhot 010018, China
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19
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Liu Y, Jiang M, Zheng Z, Yao D, Yang S, Yang C, Zhang Y, Aweya JJ. Fucosyltransferase 2 is involved in immune-related functions in Penaeus vannamei by modulating antimicrobial peptides' expression. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2023; 140:104611. [PMID: 36473550 DOI: 10.1016/j.dci.2022.104611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 06/17/2023]
Abstract
In mammals fucosyltransferase 2 (FUT2) plays an important regulatory role in inflammation, bacterial or viral infection, and tumor metastasis. However, the specific role of FUT2 in invertebrate immunity has not been reported. Here, the FUT2 homolog of Penaeus vannamei (designated as PvFUT2) was cloned and found to have a full-length cDNA of 1104 bp with an open reading frame (ORF) encoding 316 amino acids. PvFUT2 is constitutively expressed in all shrimp tissues tested with the highest found in intestines. Moreover, PvFUT2 was induced in the main immune organs (hemocytes and hepatopancreas) of shrimp by Gram-positive (Vibrio parahaemolyticus), Gram-negative (Streptococcus iniae) bacteria and virus (White Spot Syndrome Virus), indicating the involvement of PvFUT2 in shrimp antimicrobial response. Intriguingly, PvFUT2 knockdown with or without pathogen challenge reduced the expression of Pvβ-catenin and antimicrobial peptides genes, particularly anti lipopolysaccharide factor and lysozyme. Further analysis revealed that the knockdown of PvFUT2 increased Vibrio abundance in hemolymph and resulted in an increase in shrimp cumulative mortality rate. Thus, during pathogen challenge, the expression of PvFUT2 is induced to regulate β-catenin and subsequently antimicrobial peptides expression to augment shrimp antimicrobial immune response.
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Affiliation(s)
- Yiqi Liu
- Institute of Marine Sciences, Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China
| | - Mingming Jiang
- Institute of Marine Sciences, Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China
| | - Zhihong Zheng
- Institute of Marine Sciences, Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China
| | - Defu Yao
- Institute of Marine Sciences, Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China
| | - Shen Yang
- College of Ocean Food and Biological Engineering, Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Jimei University, Xiamen, 361021, Fujian, China
| | - Chunling Yang
- Guangxi Academy of Fishery Sciences, Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Nanning, 530021, China
| | - Yueling Zhang
- Institute of Marine Sciences, Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China
| | - Jude Juventus Aweya
- College of Ocean Food and Biological Engineering, Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Jimei University, Xiamen, 361021, Fujian, China.
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20
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Abstract
Lay SummaryThe article describes the hypothesis that there may be a noncausal relationship between Helicobacter pylori infection and inflammatory bowel disease (IBD) that is related to the host mucin glycan fucosylation status in the gastrointestinal tract. The proposed hypothesis may explain why IBD is less prevalent in patients with H. pylori, and no increased risk of IBD is seen after H. pylori eradication therapy, as was shown in the study by Tanner et al.
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Affiliation(s)
- Juris Pokrotnieks
- Department of Internal Diseases, Rīga Stradiņš University, Riga, Latvia
- Centre of Gastroenterology, Hepatology and Nutrition, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
| | - Stanislav Sitkin
- Department of Internal Diseases, Gastroenterology and Dietetics, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia
- Institute of Perinatology and Pediatrics, Almazov National Medical Research Centre, Saint Petersburg, Russia
- R&D Department, Elpis Ltd, Riga, Latvia
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21
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Gai X, Qian P, Guo B, Zheng Y, Fu Z, Yang D, Zhu C, Cao Y, Niu J, Ling J, Zhao J, Shi H, Liu G. Heptadecanoic acid and pentadecanoic acid crosstalk with fecal-derived gut microbiota are potential non-invasive biomarkers for chronic atrophic gastritis. Front Cell Infect Microbiol 2023; 12:1064737. [PMID: 36699724 PMCID: PMC9868245 DOI: 10.3389/fcimb.2022.1064737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 12/05/2022] [Indexed: 01/11/2023] Open
Abstract
Background Chronic atrophic gastritis (CAG), premalignant lesions of gastric cancer (GC), greatly increases the risk of GC. Gastroscopy with tissue biopsy is the most commonly used technology for CAG diagnosis. However, due to the invasive nature, both ordinary gastroscope and painless gastroscope result in a certain degree of injury to the esophagus as well as inducing psychological pressure on patients. In addition, patients need fast for at least half a day and take laxatives. Methods In this study, fecal metabolites and microbiota profiles were detected by metabolomics and 16S rRNA V4-V5 region sequencing. Results Alteration of fecal metabolites and microbiota profiles was found in CAG patients, compared with healthy volunteers. To identify the most relevant features, 7 fecal metabolites and 4 microbiota were selected by random forest (RF), from A and B sample sets, respectively. Furthermore, we constructed support vector machines (SVM) classifification model using 7 fecal metabolites or 4 gut microbes, or 7 fecal metabolites with 4 gut microbes, respectively, on C sample set. The accuracy of classifification model was 0.714, 0.857, 0.857, respectively, and the AUC was 0.71, 0.88, 0.9, respectively. In C sample set, Spearman's rank correlation analysis demonstrated heptadecanoic acid and pentadecanoic acid were signifificantly negatively correlated to Erysipelotrichaceae_UCG-003 and Haemophilus, respectively. We constructed SVM classifification model using 2 correlated fecal metabolites and 2 correlated gut microbes on C sample set. The accuracy of classification model was 0.857, and the AUC was 0.88. Conclusion Therefore, heptadecanoic acid and pentadecanoic acid, crosstalk with fecal-derived gut microbiota namely Erysipelotrichaceae_UCG-003 and Haemophilus, are potential non-invasive biomarkers for CAG diagnosis.
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Affiliation(s)
- Xiao Gai
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peng Qian
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Benqiong Guo
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yixin Zheng
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhihao Fu
- School of Computer Science, Fudan University, Shanghai, China
| | - Decai Yang
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chunmei Zhu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yang Cao
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jingbin Niu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianghong Ling
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jin Zhao
- School of Computer Science, Fudan University, Shanghai, China
| | - Hailian Shi
- Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Research Center of Shanghai Traditional Chinese Medicine Standardization, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guoping Liu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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22
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Wang P, Guo R, Bai X, Cui W, Zhang Y, Li H, Shang J, Zhao Z. Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice. Front Endocrinol (Lausanne) 2022; 13:1034818. [PMID: 36589853 PMCID: PMC9802116 DOI: 10.3389/fendo.2022.1034818] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/31/2022] [Indexed: 12/23/2022] Open
Abstract
Background Diabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles. Methods Male C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis. Results We found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment. Conclusions Sac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.
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Affiliation(s)
- Peipei Wang
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhengzhou University, Zhengzhou, China
| | - Ruixue Guo
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhengzhou University, Zhengzhou, China
| | - Xiwen Bai
- Nanchang University Queen Mary School, Nanchang, China
| | - Wen Cui
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhengzhou University, Zhengzhou, China
| | - Yiding Zhang
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhengzhou University, Zhengzhou, China
| | - Huangmin Li
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhengzhou University, Zhengzhou, China
| | - Jin Shang
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Laboratory Animal Platform of Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
- Nephropathy Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhanzheng Zhao
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Laboratory Animal Platform of Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
- Nephropathy Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Di W, Li X, Yang Q. Polysaccharide of L. casei SB27 reduced colon cancer cell prognosis through mitochondrial damage by up-regulation of HINT2. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2022. [DOI: 10.1016/j.jrras.2022.100470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Tonelli Enrico V, Vo N, Methe B, Morris A, Sowa G. An unexpected connection: A narrative review of the associations between Gut Microbiome and Musculoskeletal Pain. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2022; 31:3603-3615. [PMID: 36308543 PMCID: PMC9617047 DOI: 10.1007/s00586-022-07429-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 10/12/2022] [Accepted: 10/14/2022] [Indexed: 11/06/2022]
Abstract
PURPOSE Multiple diverse factors contribute to musculoskeletal pain, a major cause of physical dysfunction and health-related costs worldwide. Rapidly growing evidence demonstrates that the gut microbiome has overarching influences on human health and the body's homeostasis and resilience to internal and external perturbations. This broad role of the gut microbiome is potentially relevant and connected to musculoskeletal pain, though the literature on the topic is limited. Thus, the literature on the topic of musculoskeletal pain and gut microbiome was explored. METHODS This narrative review explores the vast array of reported metabolites associated with inflammation and immune-metabolic response, which are known contributors to musculoskeletal pain. Moreover, it covers known modifiable (e.g., diet, lifestyle choices, exposure to prescription drugs, pollutants, and chemicals) and non-modifiable factors (e.g., gut architecture, genetics, age, birth history, and early feeding patterns) that are known to contribute to changes to the gut microbiome. Particular attention is devoted to modifiable factors, as the ultimate goal of researching this topic is to implement gut microbiome health interventions into clinical practice. RESULTS Overall, numerous associations exist in the literature that could converge on the gut microbiome's pivotal role in musculoskeletal health. Particularly, a variety of metabolites that are either directly produced or indirectly modulated by the gut microbiome have been highlighted. CONCLUSION The review highlights noticeable connections between the gut and musculoskeletal health, thus warranting future research to focus on the gut microbiome's role in musculoskeletal conditions.
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Affiliation(s)
- Valerio Tonelli Enrico
- Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, University of Pittsburgh, 200 Lothrop Street, Room E1612, BST, Pittsburgh, PA, 15261, USA.
- Department of Physical Therapy, University of Pittsburgh, 100 Technology Dr, Pittsburgh, PA, 15219, USA.
| | - Nam Vo
- Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, University of Pittsburgh, 200 Lothrop Street, Room E1612, BST, Pittsburgh, PA, 15261, USA
| | - Barbara Methe
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, University of Pittsburgh, 1218 Scaife Hall 3550 Terrace Street, Pittsburgh, PA, 15261, USA
| | - Alison Morris
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, University of Pittsburgh, 1218 Scaife Hall 3550 Terrace Street, Pittsburgh, PA, 15261, USA
| | - Gwendolyn Sowa
- Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, University of Pittsburgh, 200 Lothrop Street, Room E1612, BST, Pittsburgh, PA, 15261, USA
- Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Kaufmann Medical Building, Suite 910, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA
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Saikia K, Saharia N, Singh CS, Borah PP, Namsa ND. Association of histo-blood group antigens and predisposition to gastrointestinal diseases. J Med Virol 2022; 94:5149-5162. [PMID: 35882942 DOI: 10.1002/jmv.28028] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 06/26/2022] [Accepted: 07/23/2022] [Indexed: 12/15/2022]
Abstract
Infectious gastroenteritis is a common illness afflicting people worldwide. The two most common etiological agents of viral gastroenteritis, rotavirus and norovirus are known to recognize histo-blood group antigens (HBGAs) as attachment receptors. ABO, Lewis, and secretor HBGAs are distributed abundantly on mucosal epithelia, red blood cell membranes, and also secreted in biological fluids, such as saliva, intestinal content, milk, and blood. HBGAs are fucosylated glycans that have been implicated in the attachment of some enteric pathogens such as bacteria, parasites, and viruses. Single nucleotide polymorphisms in the genes encoding ABO (H), fucosyltransferase gene FUT2 (Secretor/Se), FUT3 (Lewis/Le) have been associated with changes in enzyme expression and HBGAs production. The highly polymorphic HBGAs among different populations and races influence genotype-specific susceptibility or resistance to enteric pathogens and its epidemiology, and vaccination seroconversion. Therefore, there is an urgent need to conduct population-based investigations to understand predisposition to enteric infections and gastrointestinal diseases. This review focuses on the relationship between HBGAs and predisposition to common human gastrointestinal illnesses caused by viral, bacterial, and parasitic agents.
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Affiliation(s)
- Kasturi Saikia
- Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Assam, India
| | - Niruprabha Saharia
- Department of Paediatrics, Tezpur Medical College and Hospital, Bihaguri, Tezpur, Assam, India
| | - Chongtham S Singh
- Department of Paediatrics, Regional Institute of Medical Sciences, Imphal, India
| | - Partha P Borah
- Department of Paediatrics and Neonatology, Pratiksha Hospital, Guwahati, Assam, India
| | - Nima D Namsa
- Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Assam, India.,Centre for Multi-disciplinary Research, Tezpur University, Napaam, Assam, India
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Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease. Life (Basel) 2022; 12:life12101623. [PMID: 36295058 PMCID: PMC9604584 DOI: 10.3390/life12101623] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/07/2022] [Accepted: 10/08/2022] [Indexed: 11/16/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals’ genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.
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27
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Xu H, Pan LB, Yu H, Han P, Fu J, Zhang ZW, Hu JC, Yang XY, Keranmu A, Zhang HJ, Bu MM, Jiang JD, Wang Y. Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics. Front Pharmacol 2022; 13:919181. [PMID: 36238574 PMCID: PMC9551995 DOI: 10.3389/fphar.2022.919181] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/26/2022] [Indexed: 11/13/2022] Open
Abstract
The gut microbiota plays an important role in inflammatory diseases. Metabolites in the three metabolic pathways of tryptophan (Trp), histidine (His), and phenylalanine (Phe) can affect various inflammatory conditions, such as obesity, diabetes, arthritis, colitis, atherosclerosis, and neuroinflammation. We established an LC–MS/MS method to measure 17 metabolites—Trp, 3-indole-acetic acid (Iaa), 3-indole-lactate (Ila), 3-indole-propionic acid (Ipa), 3-indole formaldehyde (Iald), kynurenine (Kn), kynurenic acid (Kyna), 3-Hydroxyanthranilic acid (3-Haa), His, 3-methylhistidine (3-Mhis), histamine (Hist), imidazole propionic acid (Imp), 4-imidazoacetic acid (Imaa), urocanic acid (Ua), Phe, phenylethylamine (Pea), and hippuric acid (Ha)—in the three metabolic pathways. The method exhibited high sensitivity and good selectivity, linearity, accuracy, precision, stability; and recovery rate; all met the requirements of biological sample analysis. By establishing a rheumatoid arthritis (RA) model of Sprague–Dawley rats and performing 16S rRNA sequencing on their feces, it was found that there was dysbiosis, including changes in phylum level, genus level, and α biodiversity of gut bacteria. The contents of the microbiota metabolites Iaa and Ipa in the model group were significantly decreased, and those of Iald, Kn, Kyna, Ha, and Imp were significantly increased. The common therapeutic drugs Tripterygium glycosides, total glucosides of peony, and their main active ingredients were screened by in vitro incubation with gut bacteria: it was found that Tripterygium glycosides and their active ingredients could lead to a variation in metabolites in the Trp and Phe pathways. Total glucosides and active components of peony could lead to a variation in metabolites in the Phe pathway of the gut microbiota.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Yan Wang
- *Correspondence: Yan Wang, ; Jian-Dong Jiang,
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Shang J, Guo H, Li J, Li Z, Yan Z, Wei L, Hua Y, Lin L, Tian Y. Exploring the mechanism of action of Sanzi formula in intervening colorectal adenoma by targeting intestinal flora and intestinal metabolism. Front Microbiol 2022; 13:1001372. [PMID: 36160256 PMCID: PMC9504867 DOI: 10.3389/fmicb.2022.1001372] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 08/22/2022] [Indexed: 12/05/2022] Open
Abstract
Background Sanzi formula (SZF) is a kind of Chinese herbal compound that has a certain effect on the prevention and treatment of colorectal adenoma (CRA), which can prevent and control the process of CRA-cancer transformation. In this study, we explored the mechanism of action of SZF in anti-CRA using 16S rRNA sequencing and metabolomics technology. Methods Mice were randomly divided into three groups: Control group, Apcmin/+ model group, and SZF treatment group. Except for the Control group, which used C57BL/6 J mice, the remaining two groups used Apcmin/+ mice. The Control group and Apcmin/+ model group were treated with ultrapure water by gavage, while the SZF treatment group was treated with SZF for 12 weeks. During this period, the physical changes of mice in each group were observed. The gut microbiota was determined by high-throughput sequencing of the 16S rRNA gene, and LC-ESI-MS/MS was used for colorectal metabolomics analysis. Results Sequencing of the 16S rRNA gut flora yielded 10,256 operational taxonomic units and metabolomic analysis obtained a total of 366 differential metabolites. The intestinal flora analysis showed that SZF could improve intestinal flora disorders in Apcmin/+ mice. For instance, beneficial bacteria such as Gastranaerophilales significantly increased and harmful bacteria such as Angelakisella, Dubosiella, Muribaculum, and Erysipelotrichaceae UCG-003 substantially decreased after the SZF intervention. In addition, metabolomic data analysis demonstrated that SZF also improved the colorectal metabolic profile of Apcmin/+ mice. In Apcmin/+ mice, metabolites such as Anserine and Ectoine were typically increased after SZF intervention; in contrast, metabolites such as Taurocholic acid, Taurochenodesoxycholic acid, Hyocholic acid, Cholic acid, and Tauro-alpha-muricholic acid showed noteworthy reductions. Metabolic flora association analysis indicated that 13 differential flora and 11 differential metabolites were associated. Conclusion SZF affects the abundance of specific intestinal flora and regulates intestinal flora disorders, improves colorectal-specific metabolites, and ameliorates intestinal metabolic disorders to prevent and treat CRA. Furthermore, the application of intestinal flora and colorectal metabolomics association analysis offers new strategies to reveal the mechanism of action of herbal medicines for the treatment of intestinal diseases.
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Affiliation(s)
- Jingyu Shang
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong Guo
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Jie Li
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhongyi Li
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhanpeng Yan
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Lanfu Wei
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Yongzhi Hua
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Lin Lin
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
- *Correspondence: Lin Lin,
| | - Yaozhou Tian
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China
- Yaozhou Tian,
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Hu J, Cheng S, Yao J, Lin X, Li Y, Wang W, Weng J, Zou Y, Zhu L, Zhi M. Correlation between altered gut microbiota and elevated inflammation markers in patients with Crohn's disease. Front Immunol 2022; 13:947313. [PMID: 36045690 PMCID: PMC9420857 DOI: 10.3389/fimmu.2022.947313] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Prior studies reported inconsistent results on the altered gut microbial composition in patients with Crohn's disease (CD), likely under the influences of many confounding factors including genetic, life style and environmental variations among different study cohorts. This study aims to examine the gut microbiota of CD patients with particular efforts to minimize the impact of the confounding factors. For this purpose, the healthy relatives of the patients were enrolled as control subjects so that the paired study subjects may have similar genetic background, dietary habits, and household environment. The fecal microbiota of the study subjects were examined by 16S rRNA sequencing. After the identification of the differential bacterial genera, multivariate regression analysis was performed to adjust the results for the impact of confounding factors. We found that the microbiota of the CD patients were featured with reduced short chain fatty acid (SCFA) producing bacteria and elevated opportunistic pathogen Escherichia-Shigella. Correlation analysis indicated that the elevation in Escherichia-Shigella and the reduction in SCFA-producing bacteria usually occur simultaneously. These differential genera exhibited a high capacity in distinguishing between CD and healthy controls achieving an area under curve of 0.89, and were correlated with the changes in inflammation related blood biochemical markers. Consistent with the reduction in SCFA-producing bacteria in CD, metabolomics analysis revealed decreased blood level of SCFAs in the patients. The differential genera identified in this study demonstrated outstanding capability to serve as diagnosis markers for CD and are potential targets for intervention.
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Affiliation(s)
- Jun Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sijing Cheng
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- School of Medicine, Sun Yat-sen University, Shenzhen, China
| | - Jiayin Yao
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xutao Lin
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yichen Li
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenxia Wang
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingrong Weng
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yifeng Zou
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lixin Zhu
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Min Zhi
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Hu M, Zhang X, Li J, Chen L, He X, Sui T. Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases. Front Microbiol 2022; 13:940196. [PMID: 35923409 PMCID: PMC9339987 DOI: 10.3389/fmicb.2022.940196] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/20/2022] [Indexed: 12/26/2022] Open
Abstract
The fucosyltransferase 2 gene (FUT2) mediates the synthesis of histoblood group antigens (HBGA) that occur in vivo from multiple organs, particularly on the surface of intestinal epithelial cells and body fluids. To date, many studies have demonstrated that the interaction of HBGA with the host microbiota is the cause of pathogenesis of intestinal diseases, making FUT2 non-secretor a risk factor for inflammatory bowel disease (IBD) due to the lack of HBGA. As HBGA also acts as an attachment site for norovirus (NoV) and rotavirus (RV), the non-secretor becomes a protective factor for both viral infections. In addition, the interaction of norovirus and rotavirus with symbiotic bacteria has been found to play an important role in regulating enteroviral infection in IBD. Given the current incomplete understanding of the complex phenomenon and the underlying pathogenesis of intestinal diseases such as IBD, it has recently been hypothesized that the FUT2 gene regulates intestinal bacteria through attachment sites, may help to unravel the role of FUT2 and intestinal flora in the mechanism of intestinal diseases in the future, and provide new ideas for the prevention and treatment of intestinal diseases through more in-depth studies.
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Zhang X, Liu L, Luo J, Peng X. Anti-aging potency correlates with metabolites from in vitro fermentation of edible fungal polysaccharides using human fecal intestinal microflora. Food Funct 2022; 13:11592-11603. [DOI: 10.1039/d2fo01951e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aging is a natural process in which the structural integrity of an organism declines over time.
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Affiliation(s)
- Xiaomei Zhang
- Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Liu Liu
- Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Jianming Luo
- Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Xichun Peng
- Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China
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