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Yang Y, Zhao Z, Wu S, Yao D. Structural or functional abnormality of sphincter of Oddi: an important factor for the recurrence of choledocholithiasis after endoscopic treatment. Ann Med 2025; 57:2440119. [PMID: 39673217 PMCID: PMC11648144 DOI: 10.1080/07853890.2024.2440119] [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: 04/23/2024] [Revised: 06/15/2024] [Accepted: 11/01/2024] [Indexed: 12/16/2024] Open
Abstract
A high recurrence rate is undesirable after treatment of common bile duct (CBD) stones. A major risk factor identified for recurrence is that invasive techniques, including surgical or endoscopic treatments, will impair the biliary tract system either by direct incision of the CBD or by cutting or dilating the ampulla of Vater. During endoscopic treatment, two main assisted methods for lithotomy, sphincterotomy and papillary balloon dilation, can result in different degrees of damage to the structure and function of the sphincter of Oddi (SO), contributing to slowing of biliary excretion, cholestasis, biliary bacterial infection, and promotion of bile duct stone recurrence. In this review, the relationship between endoscopic lithotomy and structural impairment or functional abnormality of the SO will be summarized, and their relationship with the recurrence of CBD stones will also be analyzed. Further improvement of these endoscopic methods or exploration of some novel methods, such as endoscopic endoclip papilloplasty, temporary insertion of a self-expandable metal stent, and combined application of peroral cholangioscopy, may aid in providing more appropriate treatment for patients with choledocholithiasis, repair or protect the function and structure of SO, reduce or prevent the recurrence of bile duct stones, and improve patient outcomes.
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Affiliation(s)
- Ye Yang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zeying Zhao
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Shuodong Wu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Dianbo Yao
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
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Zheng X, Yan Y, Li X, Liu M, Zhao X, He J, Zhuang X. Microbial characteristics of bile in gallstone patients: a comprehensive analysis of 9,939 cases. Front Microbiol 2024; 15:1481112. [PMID: 39749136 PMCID: PMC11693992 DOI: 10.3389/fmicb.2024.1481112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 12/04/2024] [Indexed: 01/04/2025] Open
Abstract
Introduction The exact triggers of gallstone formation remain incompletely understood, but research indicates that microbial infection is a significant factor and can interfere with treatment. There is no consensus on the bile microbial culture profiles in previous studies, and determining the microbial profile could aid in targeted prevention and treatment. The primary aim of this study is to investigate the differences in microbial communities cultured from bile specimens of patients with gallstones. Methods We collected the clinical characteristics and bile microbial status of 9,939 gallstone patients. Statistical analysis was employed to assess the relationship between microbes and clinical features, and a random forest model was utilized to predict recurrence. Results Results showed a higher proportion of females among patients, with the age group of 60-74 years being the most prevalent. The most common type of gallstone was solitary gallbladder stones. A total of 76 microbes were cultured from 5,153 patients, with Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis being the most frequently identified. Significant differences in microbial diversity and positive detection rates were observed across different age groups, types of gallstones, and recurrence status. Positive frequencies of E. coli, Enterococcus faecium, and K. pneumoniae varied significantly by age group and gallstone type. The microbial diversity in the recurrence group was significantly lower compared to the non-recurrence group. The recurrence rate was significantly higher in the group with single microbial species compared to those with no microbes or multiple microbes. For the recurrence group, there were significant differences in the frequencies of seven microbes (Aeromonas hydrophila, Enterococcus casseliflavus, Enterococcus faecium, E. coli, K. pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) before and after recurrence, with these microbes appearing in a higher number of patients after recurrence. Regression analysis identified patient age, stone size, diabetes, venous thrombosis, liver cirrhosis, malignancy, coronary heart disease, and the number of microbial species as important predictors of recurrence. A random forest model constructed using these variables demonstrated good performance and high predictive ability (ROC-AUC = 0.862). Discussion These findings highlight the significant role of microbial communities in gallstone formation and recurrence. Furthermore, the identified predictors of recurrence, including clinical factors and microbial diversity, may help develop personalized prevention and recurrence strategies for gallstone patients.
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Affiliation(s)
- Xin Zheng
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Yunjun Yan
- Jinan Dian Medical Laboratory CO., LTD, Jinan, China
| | - Xin Li
- Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Mimin Liu
- Jinan Dian Medical Laboratory CO., LTD, Jinan, China
| | - Xiaoyue Zhao
- Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Jing He
- Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Xuewei Zhuang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory for Precision Medicine, Jinan, Shandong, China
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Zhao Z, Yang Y, Wu S, Yao D. Role of Secretory Mucins in the Occurrence and Development of Cholelithiasis. Biomolecules 2024; 14:676. [PMID: 38927079 PMCID: PMC11201413 DOI: 10.3390/biom14060676] [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: 04/21/2024] [Revised: 05/19/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.
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Affiliation(s)
| | | | | | - Dianbo Yao
- Department of General Surgery, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Heping District, Shenyang 110004, China; (Z.Z.); (Y.Y.); (S.W.)
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Sun Y, Xu C, Luo J, Li S, Chen S, Cen Y, Xu P. Comprehensive analysis of differential long non-coding RNA and messenger RNA expression in cholelithiasis using high-throughput sequencing and bioinformatics. Front Genet 2024; 15:1375019. [PMID: 38808330 PMCID: PMC11130440 DOI: 10.3389/fgene.2024.1375019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/24/2024] [Indexed: 05/30/2024] Open
Abstract
Background The etiology of gallstone disease (GSD) has not been fully elucidated. Consequently, the primary objective of this study was to scrutinize and provisionally authenticate the distinctive expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in GSD. Methods RiboNucleic Acid (RNA) sequencing was used on four paired human gallbladder samples for the purpose of this study. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified and subjected to analysis of their biological functions. The Pearson's correlation coefficients between DElncRNAs and DEmRNAs were computed to construct a co-expression network delineating their associations. Furthermore, both cis- and trans-regulatory networks of selected lncRNAs were established and visualized. Additionally, a competing endogenous RNA (ceRNA) regulatory network was constructed. To validate the RNA-sequencing data, we performed a Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) on 10 paired human gallbladder samples, assessing the expressions of the top 4 DEmRNAs and DElncRNAs in gallstone and control samples. Results A total of 934 DEmRNAs and 304DElncRNAs were successfully identified. Functional enrichment analysis indicated a predominant involvement in metabolic-related biological functions. Correlation analysis revealed a strong association between the expressions of 597 DEmRNAs and 194 DElncRNAs. Subsequently, both a cis-lncRNA-mRNA and a trans-lncRNA-Transcription Factor (TF)-mRNA regulatory network were meticulously constructed. Additionally, a ceRNA network, comprising of 24 DElncRNAs, 201 DEmRNAs, and 120 predicted miRNAs, was established. Furthermore, using RT-qPCR, we observed significant upregulation of AC004692.4, HECW1-IT1, SFRP4, and COMP, while LINC01564, SLC26A3, RP1-27K12.2, and GSTA2 exhibited marked downregulation in gallstone samples. Importantly, these findings were consistent with the sequencing. Conclusion We conducted a screening process to identify DElncRNAs and DEmRNAs in GSD. This approach contributes to a deeper understanding of the genetic factors involved in the etiology of gallstones.
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Affiliation(s)
- Yanbo Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Conghui Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
- School of Medicine, Yunnan University, Kunming, China
| | - Jing Luo
- Department of Gastrointestinal Surgery, Qujing No. 1 People’s Hospital, Qujing, Yunnan, China
| | - Shumin Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shi Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yunyun Cen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Pengyuan Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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Yu J, He Y, Yao W, Liu T, Liu X, Zheng Y, Hao C, Xue D. Helicobacter pylori CagA Promotes the Formation of Gallstones by Increasing the Permeability of Gallbladder Epithelial Cells. Helicobacter 2024; 29:e13100. [PMID: 38873839 DOI: 10.1111/hel.13100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/21/2024] [Accepted: 05/22/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms. METHODS scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation. RESULTS Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation. CONCLUSIONS Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.
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Affiliation(s)
- Jingjing Yu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yuanhang He
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wenchao Yao
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Tianming Liu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xuxu Liu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yi Zheng
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chenjun Hao
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dongbo Xue
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Wang S, Bao C, Pei D. Application of Data Mining Technology in the Screening for Gallbladder Stones: A Cross-Sectional Retrospective Study of Chinese Adults. Yonsei Med J 2024; 65:210-216. [PMID: 38515358 PMCID: PMC10973557 DOI: 10.3349/ymj.2023.0246] [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: 06/26/2023] [Revised: 08/21/2023] [Accepted: 11/07/2023] [Indexed: 03/23/2024] Open
Abstract
PURPOSE The purpose of this study was to use data mining methods to establish a simple and reliable predictive model based on the risk factors related to gallbladder stones (GS) to assist in their diagnosis and reduce medical costs. MATERIALS AND METHODS This was a retrospective cross-sectional study. A total of 4215 participants underwent annual health examinations between January 2019 and December 2019 at the Physical Examination Center of Shengjing Hospital Affiliated to China Medical University. After rigorous data screening, the records of 2105 medical examiners were included for the construction of J48, multilayer perceptron (MLP), Bayes Net, and Naïve Bayes algorithms. A ten-fold cross-validation method was used to verify the recognition model and determine the best classification algorithm for GS. RESULTS The performance of these models was evaluated using metrics of accuracy, precision, recall, F-measure, and area under the receiver operating characteristic curve. Comparison of the F-measure for each algorithm revealed that the F-measure values for MLP and J48 (0.867 and 0.858, respectively) were not statistically significantly different (p>0.05), although they were significantly higher than the F-measure values for Bayes Net and Naïve Bayes (0.824 and 0.831, respectively; p<0.05). CONCLUSION The results of this study showed that MLP and J48 algorithms are effective at screening individuals for the risk of GS. The key attributes of data mining can further promote the prevention of GS through targeted community intervention, improve the outcome of GS, and reduce the burden on the medical system.
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Affiliation(s)
- Shuang Wang
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chenhui Bao
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dongmei Pei
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China.
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Lee J, Park JS. The gut microbiome predicts response to UDCA/CDCA treatment in gallstone patients: comparison of responders and non-responders. Sci Rep 2024; 14:2534. [PMID: 38291113 PMCID: PMC10828362 DOI: 10.1038/s41598-024-53173-2] [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: 07/27/2023] [Accepted: 01/29/2024] [Indexed: 02/01/2024] Open
Abstract
The treatment of gallbladder (GB) stones depends on condition severity. Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are commonly used to treat GB stones, but the factors affecting response rates have not been fully identified. Therefore, we investigated the relationship between response to UDCA/CDCA treatment and changes in the gut microbiomes of patients with GB stones with the intention of identifying gut microbiomes that predict susceptibility to UDCA/CDCA treatment and treatment response. In this preliminary, prospective study, 13 patients with GB stones were treated with UDCA/CDCA for 6 months. Patients were classified into responder and non-responder groups based on treatment outcomes. Gut microbiomes were analyzed by 16S rDNA sequencing. Taxonomic compositions and abundances of bacterial communities were analyzed before and after UDCA/CDCA treatment. Alpha and beta diversities were used to assess similarities between organismal compositions. In addition, PICRUSt2 analysis was conducted to identify gut microbial functional pathways. Thirteen patients completed the treatment; 8 (62%) were assigned to the responder group and the remainder to the non-responder group. Low abundances of the Erysipelotrichi lineage were significantly associated with favorable response to UDCA/CDCA treatment, whereas high abundances of Firmicutes phylum indicated no or poor response. Our results suggest that a low abundance of the Erysipelotrichi lineage is significantly associated with a favorable response to UDCA/CDCA and that a high abundance of Firmicutes phylum is indicative of no or poor response. These findings suggest that some gut microbiomes are susceptible to UDCA/CDCA treatment and could be used to predict treatment response in patients with GB stones.
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Affiliation(s)
- Jungnam Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Jin-Seok Park
- Department of Internal Medicine, Digestive Disease Center, Shihwa Medical Center, 381, Gunjacheon-ro, Siheung-si, Gyeonggi-do, South Korea.
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Shukla R, Chadha M, Shekh R, Tiwari RK. Role of probiotics in gallstone treatment. GALLSTONE FORMATION, DIAGNOSIS, TREATMENT AND PREVENTION 2024:169-187. [DOI: 10.1016/b978-0-443-16098-1.00006-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Yang XT, Wang J, Jiang YH, Zhang L, Du L, Li J, Liu F. Insight into the mechanism of gallstone disease by proteomic and metaproteomic characterization of human bile. Front Microbiol 2023; 14:1276951. [PMID: 38111640 PMCID: PMC10726133 DOI: 10.3389/fmicb.2023.1276951] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 11/16/2023] [Indexed: 12/20/2023] Open
Abstract
Introduction Cholesterol gallstone disease is a prevalent condition that has a significant economic impact. However, the role of the bile microbiome in its development and the host's responses to it remain poorly understood. Methods In this study, we conducted a comprehensive analysis of microbial and human bile proteins in 40 individuals with either gallstone disease or gallbladder polyps. We employed a combined proteomic and metaproteomic approach, as well as meta-taxonomic analysis, functional pathway enrichment, and Western blot analyses. Results Our metaproteomic analysis, utilizing the lowest common ancestor algorithm, identified 158 microbial taxa in the bile samples. We discovered microbial taxa that may contribute to gallstone formation, including β-glucuronidase-producing bacteria such as Streptococcus, Staphylococcus, and Clostridium, as well as those involved in biofilm formation like Helicobacter, Cyanobacteria, Pseudomonas, Escherichia coli, and Clostridium. Furthermore, we identified 2,749 human proteins and 87 microbial proteins with a protein false discovery rate (FDR) of 1% and at least 2 distinct peptides. Among these proteins, we found microbial proteins crucial to biofilm formation, such as QDR3, ompA, ndk, pstS, nanA, pfIB, and dnaK. Notably, QDR3 showed a gradual upregulation from chronic to acute cholesterol gallstone disease when compared to polyp samples. Additionally, we discovered other microbial proteins that enhance bacterial virulence and gallstone formation by counteracting host oxidative stress, including sodB, katG, rbr, htrA, and ahpC. We also identified microbial proteins like lepA, rtxA, pckA, tuf, and tpiA that are linked to bacterial virulence and potential gallstone formation, with lepA being upregulated in gallstone bile compared to polyp bile. Furthermore, our analysis of the host proteome in gallstone bile revealed enhanced inflammatory molecular profiles, including innate immune molecules against microbial infections. Gallstone bile exhibited overrepresented pathways related to blood coagulation, folate metabolism, and the IL-17 pathway. However, we observed suppressed metabolic activities, particularly catabolic metabolism and transport activities, in gallstone bile compared to polyp bile. Notably, acute cholelithiasis bile demonstrated significantly impaired metabolic activities compared to chronic cholelithiasis bile. Conclusion Our study provides a comprehensive metaproteomic analysis of bile samples related to gallstone disease, offering new insights into the microbiome-host interaction and gallstone formation mechanism.
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Affiliation(s)
- Xue-Ting Yang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Jie Wang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Ying-Hua Jiang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Lei Zhang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Ling Du
- Key Laboratory of Digestive Cancer Full Cycle Monitoring and Precise Intervention of Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, Shanghai, China
| | - Jun Li
- Department of Surgery, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Feng Liu
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
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Wu S, Zhu W, Wang X, Zhao K, He B, Peng Z, Yang J. Relationship between different intestinal microflora and cholelithiasis: A systematic review and meta-analysis. Asian J Surg 2023; 46:4780-4782. [PMID: 37328378 DOI: 10.1016/j.asjsur.2023.05.091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 05/19/2023] [Indexed: 06/18/2023] Open
Affiliation(s)
- Shile Wu
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China; Soochow University, Suzhou, 21500, Jiangsu Province, China
| | - Wenjun Zhu
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China
| | - Xinsheng Wang
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China
| | - Kechang Zhao
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China
| | - Beibei He
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China
| | - Zhe Peng
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China
| | - Jinyu Yang
- Department of General Surgery, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China
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Cai X, Peng Y, Gong Y, Huang X, Liu L, Chen Y, Du J, Dai Z, Qian Y, Xu L. Variations of bile bacterial community alongside gallstone disease progression and key taxa involved in poor outcomes after endoscopic surgery. Eur J Med Res 2023; 28:313. [PMID: 37660138 PMCID: PMC10474685 DOI: 10.1186/s40001-023-01308-y] [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: 09/27/2022] [Accepted: 08/21/2023] [Indexed: 09/04/2023] Open
Abstract
Gallstone disease is a prevalent biliary disease worldwide, and bacteria play vital roles in the disease development and progression, as well as the prognosis after endoscopic surgery. However, there have been limited studies to explore the key taxa involved. In this study, bile samples from healthy controls (HCs, liver donors without hepatobiliary disease) and three diseased groups, namely patients with gallbladder stones (GBS), patients with common bile duct stones (CBDS), and patients with stricture in the common bile duct (SCBD), were collected and analyzed. Bacterial community characterization based on 16S rRNA amplicon sequencing showed that bacterial diversities did not change significantly alongside gallstone disease development and progression. The predominant phyla in each group were Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota, representing over 80% in abundance of the biliary bacteria community. Specifically, the abundance of Proteobacteria decreased greatly while that of Firmicutes and Bacteroidota increased greatly in the diseased groups when compared to that in HCs. Moreover, linear discriminant analysis identified several genera highly represented in the diseased groups. Among them, Klebsiella, Prevotella, Pseudomonas and Veillonella are persistent in both the HCs group and the diseased groups, indicating an enrichment of local bile bacteria in the diseased bile; while Lachnoanerobaculum, Atopobium, Oribacterium, and Stomatobaculum, those aligned to oral cavity taxa, are persistent in the diseased groups but are transient in the HCs group, and their abundances sequentially increased with the disease development and progression (HCs→GBS→CBDS→SCBD), implying a translocation and colonization of the oral cavity bacteria in the diseased bile. Moreover, co-occurrence network analysis revealed that bacterial infection (e.g., Photobacterium and Plesiomonas) from the intestine was developed during endoscopic surgery with reduced bile bacteria diversity. The results of this study revealed that the bile bacterial community is relatively stable and dominated by a few persistent taxa. Moreover, we hypothesized that translocation and colonization of specific bacteria from the oral cavity happens alongside gallstone disease development and progression, and bacterial infection from the intestinal tract results in poor outcomes after endoscopic surgery.
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Affiliation(s)
- Xunchao Cai
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Yao Peng
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Yajie Gong
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Xiuting Huang
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Lu Liu
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Yifan Chen
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Jingfeng Du
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Zhongming Dai
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Yun Qian
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China
| | - Long Xu
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, 518055, China.
- Marshall Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen, 518055, China.
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Ding L, Wang S, Jiang W, Miao Y, Liu W, Yang F, Zhang J, Chi W, Liu T, Liu Y, Wang S, Zhang Y, Zhao H. Identification of Intestinal Microbial Community in Gallstone Patients with Metagenomic Next-Generation Sequencing. Diagnostics (Basel) 2023; 13:2712. [PMID: 37627971 PMCID: PMC10453932 DOI: 10.3390/diagnostics13162712] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/14/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Gallstone disease (GD) is one of the most common gastrointestinal diseases worldwide. Nowadays, intestinal microbiota are thought to play important roles in the formation of gallstones. In our study, human fecal samples were extracted for metagenomic next-generation sequencing (mNGS) on the Illumina HiSeq platform, followed by bioinformatics analyses. Our results showed that there was a particular intestinal micro-ecosystem in GD patients. In contrast to healthy people, the sequences of Bacteroidetes, Bacteroides and Thetaiotaomicron were obviously more abundant in GD patients at phylum, genus and species levels, respectively. On the other hand, the glycan metabolism and drug resistance, especially for the β-lactams, were the most profound functions of gut microbes in GD patients compared to those in normal subjects. Furthermore, a correlation analysis drew out that there existed a significant relationship between the serum levels of biochemical indicators and abundances of intestinal microbes in GD patients. Our results illuminate both the composition and functions of intestinal microbiota in GD patients. All in all, our study can broaden the insight into the potential mechanism of how gut microbes affect the progression of gallstones to some extent, which may provide potential targets for the prevention, diagnosis or treatment of GD.
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Affiliation(s)
- Li Ding
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Su Wang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Wenrong Jiang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Yingxin Miao
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Wenjian Liu
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Feng Yang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Jinghao Zhang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Wenjing Chi
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Tao Liu
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Yue Liu
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Shiwen Wang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Yanmei Zhang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
| | - Hu Zhao
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China
- Department of Laboratory Medicine, Huadong Hospital, Shanghai 200040, China
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13
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Lee J, Jeong HJ, Kim H, Park JS. The Role of the Bile Microbiome in Common Bile Duct Stone Development. Biomedicines 2023; 11:2124. [PMID: 37626621 PMCID: PMC10452286 DOI: 10.3390/biomedicines11082124] [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: 06/18/2023] [Revised: 07/20/2023] [Accepted: 07/24/2023] [Indexed: 08/27/2023] Open
Abstract
INTRODUCTION Common bile duct (CBD) stones are a health concern for 10-20% of individuals with symptomatic gallstones, leading to health complications and placing a burden on healthcare systems. This study was initiated to investigate the changes in microbiome compositions and the metabolic signature associated with CBD stones. The research approach integrated taxonomic and functional data with metabolomics data, complemented by in vivo experiments. METHODS In a single tertiary healthcare institution, a total of 25 patients were enrolled who had undergone endoscopic retrograde cholangiopancreatography (ERCP) between February 2019 and January 2021. We harvested DNA from bile samples acquired from these individuals. The amplification of the bacterial 16S rRNA gene V3-V4 region was conducted through polymerase chain reaction (PCR), followed by sequencing. We utilized QIIME2 for a comprehensive data analysis. Furthermore, we performed a metabolomic analysis of the bile samples using nuclear magnetic resonance (NMR) spectroscopy. For the assessment of functional gene enrichment, we employed MetaboAnalyst 5.0. Lastly, we executed in vivo experiments on C57BL/6 mice and undertook histological examinations of tissue samples. RESULTS Out of the 25 study subjects, 17 underwent ERCP due to CBD stones (the CBD stone group), while the remaining 8 had the procedure for different reasons (the non-CBD stone group). An alpha diversity analysis showed a significantly greater microbial diversity in the bile samples of the non-CBD stone group (p < 0.01), and a beta diversity analysis confirmed the greater microbial compositional abundance in the gut microbiomes in this group (p = 0.01). A taxonomic analysis revealed that the abundances of Enterococcaceae and Enterococcus were higher in the bile microbiomes of the CBD stone group. A metabolic profile analysis showed that the acetate, formate, and asparagine levels were higher in the CBD stone group. A pathway enrichment analysis showed the metabolic pathways (Arginine and Proline Metabolism, Aspartate Metabolism, Glycine, and Serine Metabolism, and Ammonia Recycling pathways) that were associated with these differences. Preclinical experiments demonstrated systemic inflammation and extracellular trap formation in the CBD stone group. CONCLUSIONS Our study highlights the importance of biliary dysbiosis and bile metabolites, specifically acetate and formate, in CBD stone development and progression. These findings have implications for the development of diagnostic and therapeutic strategies using microbiomes for CBD stones.
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Affiliation(s)
| | | | | | - Jin-Seok Park
- Digestive Disease Center, Department of Internal Medicine, Inha University College of Medicine, Inha University Hospital, Incheon 22332, Republic of Korea; (J.L.); (H.J.J.); (H.K.)
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14
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Mo P, Chen H, Jiang X, Hu F, Zhang F, Shan G, Chen W, Li S, Xu G. Effect of hepatic NPC1L1 on cholesterol gallstone disease and its mechanism. Heliyon 2023; 9:e15757. [PMID: 37159680 PMCID: PMC10163659 DOI: 10.1016/j.heliyon.2023.e15757] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/11/2023] Open
Abstract
Cholesterol gallstone disease (CGD) is associated with bile cholesterol supersaturation. The Niemann-Pick C1-like 1 (NPC1L1), the inhibitory target of ezetimibe (EZE), is a critical sterol transporter of cholesterol absorption. Intestinal NPC1L1 facilitates the absorption of cholesterol, whereas hepatic NPC1L1 promotes cholesterol uptake by hepatocytes and reduces bile cholesterol supersaturation. The potential of hepatic NPC1L1 to prevent CGD has yet to be established due to its absence in the mice model. In this study, we generated mice expressing hepatic NPC1L1 using adeno-associated virus (AAV) gene delivery. The biliary cholesterol saturations and gallstone formations were explored under chow diet and lithogenic diet (LD) with or without EZE treatment. The long-term (8-week) LD-fed AAV-mNPC1L1 mice exhibited no significant differences in biliary cholesterol saturation and gallstone formation compared to WT mice. EZE effectively prevented CGD in both WT and AAV-mNPC1L1 mice. Mechanistically, prolonged LD feeding induced the degradation of hepatic NPC1L1, whereas short-term (2-week) LD feeding preserved the expression of hepatic NPC1L1. In conclusion, our findings suggest that hepatic NPC1L1 is unable to prevent CGD, whereas EZE functions as an efficient bile cholesterol desaturator during CGD development.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Guoqiang Xu
- Corresponding author. Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310006, Zhejiang, China.
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15
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Wang S, Lu Q, Zhou Y, Zhang H. Efficacy and safety of endoscopic retrograde cholangiopancreatography in patients over 75 years of age. J Minim Access Surg 2023; 19:193-201. [PMID: 37056083 PMCID: PMC10246631 DOI: 10.4103/jmas.jmas_325_21] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/08/2021] [Accepted: 01/31/2022] [Indexed: 04/15/2023] Open
Abstract
Background To investigate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in elderly choledocholithiasis patients compared with younger groups. Methods This was a case-control study conducted from January 2018 to December 2020 at Fuyang People's Hospital, with 596 patients included. Patients who underwent ERCP were classified as two groups based on age stratification definitions from the National Institute of Health and the World Health Organisation: Patients <75 ages (n = 204) and patients ≥75 ages (n = 392). Demographic characteristics, details of endoscopic therapy, complications were retrospectively reviewed and compared between two groups. The subgroup was pre-formed to further explore the efficacy and safety of ERCP in the elderly population. Results Between patients ≥75 ages and patients <75 ages, there were no significant differences in the complete stone removal rate and a second ERCP. Intubation difficulty (odds rate [OR]: 1.723, 95% confidence interval [CI]: 1.118-2.657) and longer ERCP operation time (β = 4.314, 95% CI: 2.366-6.262) were observed in the elderly group at a higher frequency than the younger group. Elder patients were more likely to have intra-operative complications (χ2 = 18.158, P < 0.001), and post-operative complications (χ2 = 8.739, P = 0.003). In the subgroup group, ERCP was efficacious and safe in elderly patients with comorbidities. Conclusions ERCP may be efficaciously performed on elderly patients. However, intra-operative and post-operative complications of ECRP should also be taken into consideration when selecting therapeutic options.
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Affiliation(s)
- Shuangping Wang
- Department of Gastroenterology, Fuyang People’s Hospital, Fuyang, P.R. China
| | - Qifeng Lu
- Department of Gastroenterology, Fuyang People’s Hospital, Fuyang, P.R. China
| | - Yabai Zhou
- Department of Gastroenterology, Fuyang People’s Hospital, Fuyang, P.R. China
| | - Hao Zhang
- Department of Clinical Medicine, Wannan Medical College, Wuhu, P.R. China
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Yang Y, Wang Y, Wang C, Wu S, Yao D. Macrophages and derived-TNF-α promote lipopolysaccharide-induced upregulation of endogenous β-glucuronidase in the epithelial cells of the bile duct: A possible facilitator of hepatolithiasis formation. Clin Res Hepatol Gastroenterol 2023; 47:102062. [PMID: 36473630 DOI: 10.1016/j.clinre.2022.102062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 10/21/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatolithiasis is prevalent in Southeast Asian regions, and the role of endogenous β-glucuronidase (β-GD) in the formation of hepatolithiasis is being gradually recognised. Revealing the regulation mechanism of the expression of endogenous β-GD will provide new therapeutic strategies for intervening in the formation of hepatolithiasis. METHODS Liver specimens from patients with hepatolithiasis were examined by immunohistochemistry to assess the expression of macrophage markers including CD68, CD80, and CD206, as well as that of TNF-α and endogenous β-GD, compared with that in normal liver samples. HiBEpiC cells were co-cultured directly or indirectly with induced M2 macrophages or directly stimulated with TNF-α, and the expression of the endogenous β-GD was examined. A PKC inhibitor, chelerythrine, and an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), were used to elucidate the possible regulation mechanism. RESULTS The expression of macrophage markers including CD68 and CD206, as well as that of TNF-α and endogenous β-GD significantly increased in liver specimens from patients with hepatolithiasis compared with that in normal liver samples. The expression of CD68, CD206 and TNF-α was positively correlated with that of endogenous β-GD. When HiBEpiC cells were co-cultured directly or indirectly with M2 macrophages, following stimulation with lipopolysaccharide (LPS), the expression of endogenous β-GD was significantly higher in the indirect co-culture group than that in the direct co-culture group, or in HiBEpiC cells or M2 macrophages cultured alone. Further experiments revealed that following stimulation with LPS, TNF-α secretion increased in both the indirect and direct co-culture groups compared with that in HiBEpiC cells cultured alone. TNF-α increased the expression of endogenous β-GD in HiBEpiC cells, in a dose- and time-dependent manner. In addition, TNF-α significantly increased the expression levels of p-P65 and proliferating cell nuclear antigen (PCNA), and PDTC effectively inhibited the TNF-α-induced expression of PCNA and β-GD. CONCLUSIONS Infiltration of macrophages, especially M2 macrophages, may be involved in the hepatolithiasis formation. LPS activates the macrophages, inducing the secretion of TNF-α, which can further increase the expression of endogenous β-GD in the epithelial cells of the bile duct, possibly via the NF-κB/PCNA signalling cascade.
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Affiliation(s)
- Ye Yang
- Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China
| | - Yang Wang
- Department of Pathology, Shenyang DI'AN Medical Testing Company Limited, Shenyang, Liaoning, China
| | - Cuifang Wang
- Department of Pathology, Shenyang DI'AN Medical Testing Company Limited, Shenyang, Liaoning, China
| | - Shuodong Wu
- Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China
| | - Dianbo Yao
- Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
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17
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Lee J, Park JS, Bae J, Lee S, Hwang Y. Bile Microbiome in Patients with Recurrent Common Bile Duct Stones and Correlation with the Duodenal Microbiome. Life (Basel) 2022; 12:life12101540. [PMID: 36294975 PMCID: PMC9605223 DOI: 10.3390/life12101540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 09/28/2022] [Accepted: 09/30/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Common bile duct (CBD) stone recurrence is a common late adverse event after CBD stone treatment. In this preliminary study, we compared the bile fluid and duodenum microbial profiles of patients with or without recurrent CBD stones to identify risk factors associated with recurrence. METHODS Bile fluid samples of 47 consecutive patients who underwent ERCP for biliary diseases were subjected to microbiome analysis. Nineteen patients were stone-recurrent (SR), and 28 patients were non-stone-recurrent (NSR). Paired samples (duodenum biopsy tissue and bile fluid samples) from five SR patients were used to compare microbiome compositions in the biliary system and duodenum. In addition, we compared the microbiome compositions of these duodenal tissue samples with those 12 controls (gastric ulcer patients without recurrent CBD stones). RESULTS Enterococcaceae_unclassified and enterococcus were more abundant in bile fluid in the SR group than in the NSR group (p = 0.002 and p = 0.003, respectively). A comparison of the microbiome compositions of duodenum tissue and bile fluid samples of the five recurrent CBD stone patients revealed proteobacteria compositions were almost identical from the phylum to genus level. In these five patients, alpha and beta diversities were no different in bile fluid and duodenal tissues. Furthermore, a comparison of the microbiome compositions of duodenal mucosa in patients with recurrent CBD stone patients (n = 5) and controls (n = 12) revealed significant differences between microbiome compositions. CONCLUSIONS Enterococcus seems to contribute to CBD stone development. Furthermore, our results indicate that retrograde migration of the duodenal microbiome may contribute to bile microbiome alterations. We recommend that more research be conducted to confirm this hypothesis.
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Affiliation(s)
- Jungnam Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Korea
| | - Jin-Seok Park
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Korea
- Correspondence: ; Tel.: +82-32-890-2548; Fax: +82-32-890-2549
| | - Jaewoong Bae
- Research and Development Institute, BioEleven Co., Ltd., Seoul 06220, Korea
| | - Sohee Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Korea
| | - Yeonju Hwang
- Research and Development Institute, BioEleven Co., Ltd., Seoul 06220, Korea
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Jiao JY, Zhu XJ, Zhou C, Wang P. Research progress on the immune microenvironment of the gallbladder in patients with cholesterol gallstones. World J Gastrointest Surg 2022; 14:887-895. [PMID: 36185563 PMCID: PMC9521471 DOI: 10.4240/wjgs.v14.i9.887] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 08/19/2022] [Accepted: 09/07/2022] [Indexed: 02/07/2023] Open
Abstract
Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades. However, the mechanism of cholesterol gallstone formation is not fully understood, so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones. The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors, among which genetic susceptibility, intestinal microflora disorders, impaired gallbladder motility, and immune disorders are important in the pathogenesis of cholesterol gallstones. This review focuses on recent advances in these mechanisms. We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones, which may be hot areas in the future.
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Affiliation(s)
- Jing-Yi Jiao
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
- Medical School, Nantong University, Nantong 226001, Jiangsu Province, China
| | - Xiao-Jun Zhu
- Department of Hepatobiliary Surgery, Nantong First People's Hospital, Nantong 226001, Jiangsu Province, China
| | - Chun Zhou
- Department of General Practitioner, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Peng Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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Di Carlo P, Serra N, Alduina R, Guarino R, Craxì A, Giammanco A, Fasciana T, Cascio A, Sergi CM. A systematic review on omics data (metagenomics, metatranscriptomics, and metabolomics) in the role of microbiome in gallbladder disease. Front Physiol 2022; 13:888233. [PMID: 36111147 PMCID: PMC9468903 DOI: 10.3389/fphys.2022.888233] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/11/2022] [Indexed: 12/04/2022] Open
Abstract
Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions affecting the health of the host. However, difficulties hamper the investigation of microbiota composition in cultivating microorganisms in standard growth media. For this reason, our knowledge of microbiota can benefit from the analysis of microbial macromolecules (DNA, transcripts, proteins, or by-products) present in various samples collected from the host. Various omics technologies are used to obtain different data. Metagenomics provides a taxonomical profile of the sample. It can also be used to obtain potential functional information. At the same time, metatranscriptomics can characterize members of a microbiome responsible for specific functions and elucidate genes that drive the microbiotas relationship with its host. Thus, while microbiota refers to microorganisms living in a determined environment (taxonomy of microorganisms identified), microbiome refers to the microorganisms and their genes living in a determined environment and, of course, metagenomics focuses on the genes and collective functions of identified microorganisms. Metabolomics completes this framework by determining the metabolite fluxes and the products released into the environment. The gallbladder is a sac localized under the liver in the human body and is difficult to access for bile and tissue sampling. It concentrates the bile produced in the hepatocytes, which drains into bile canaliculi. Bile promotes fat digestion and is released from the gallbladder into the upper small intestine in response to food. Considered sterile originally, recent data indicate that bile microbiota is associated with the biliary tract’s inflammation and carcinogenesis. The sample size is relevant for omic studies of rare diseases, such as gallbladder carcinoma. Although in its infancy, the study of the biliary microbiota has begun taking advantage of several omics strategies, mainly based on metagenomics, metabolomics, and mouse models. Here, we show that omics analyses from the literature may provide a more comprehensive image of the biliary microbiota. We review studies performed in this environmental niche and focus on network-based approaches for integrative studies.
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Affiliation(s)
- Paola Di Carlo
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Infectious Disease, University of Palermo, Palermo, Italy
| | - Nicola Serra
- Department of Public Health, University “Federico II”, Naples, Italy
| | - Rosa Alduina
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Riccardo Guarino
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | - Anna Giammanco
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Microbiology, University of Palermo, Palermo, Italy
| | - Teresa Fasciana
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Microbiology, University of Palermo, Palermo, Italy
| | - Antonio Cascio
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Infectious Disease, University of Palermo, Palermo, Italy
| | - Consolato M. Sergi
- Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON, Canada
- Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
- *Correspondence: Consolato M. Sergi,
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Weerakoon H, Vithanage I, Alahakoon O, Weerakoon K. Clinico-epidemiology and aetiopathogenesis of gallstone disease in the South Asian region: a scoping review protocol. BMJ Open 2022; 12:e057808. [PMID: 35697449 PMCID: PMC9196176 DOI: 10.1136/bmjopen-2021-057808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 05/16/2022] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Pathogenesis of gallstones (GS) is multifactorial and is influenced by numerous environmental and genetic risk factors. As a result, clinico-epidemiology and aetiopathogenesis of GS vary in different populations. Understanding the aetiopathogenesis of GS for different populations is imperative in control and prevention of GS disease and its associated complications. This protocol describes the methodology of a scoping review which focuses on synthesising the most updated knowledge on GS disease in South Asia. METHODS AND ANALYSIS The scoping review proposed in this protocol will be guided by Arksey and O'Malley's framework and the Joanna Briggs Institute Reviewers' Manual. Accordingly, population, concept and context strategy will be used to formulate the scoping review question, eligibility criteria and search strategy. In the search, electronic databases, MEDLINE/PubMed, ScienceDirect, Scopus, Cochrane library, CINAHL, Trip, and Google scholar, as well as various grey literature sources will be used in synthesising and presenting the findings on clinico-epidemiology and aetiopathogenesis of GS disease in South Asia. ETHICS AND DISSEMINATION As secondary data will be used in the study, ethical approval will not be required. The scoping review proposed by this protocol will accurately summarise the current knowledge on GS disease in South Asia based on published and unpublished literature on the field. Thus, the evidence presented in the review will be important for healthcare providers to make decisions on the control and prevention of GS disease and as well as to identify future research priorities on GS disease in South Asia.
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Affiliation(s)
- Harshi Weerakoon
- Department of Biochemistry, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| | - Ishari Vithanage
- Department of Biochemistry, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| | - Oshadhi Alahakoon
- Department of Biochemistry, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| | - Kosala Weerakoon
- Department of Parasitology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
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21
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Song ST, Cai LY, Zeng X, Xie WF. Gut Microbial Profile in Asymptomatic Gallstones. Front Microbiol 2022; 13:882265. [PMID: 35770155 PMCID: PMC9234526 DOI: 10.3389/fmicb.2022.882265] [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: 02/28/2022] [Accepted: 05/16/2022] [Indexed: 11/30/2022] Open
Abstract
There are few studies on the changes of gut microbiota in patients with gallstones, especially in patients with asymptomatic gallstones, and there are some deficiencies in these studies, for instance, the effects of metabolic factors on gut microbiota are not considered. Here, we selected 30 asymptomatic gallstone patients from the survey population, and 30 controls according to the age and BMI index matching principle. The 16SrDNA technology was used to detect and compare the structural differences in the gut microbiota between the two groups. Compared with healthy controls, the abundance of gut microbiota in patients with gallstones increased significantly, while the microbiota diversity decreased. At the level of phylum, both groups were dominated by Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria. At the genus level, there were 15 species with significant differences in abundance between the two groups. Further subgroup analysis found that only unclassified Lactobacillales showed differences in the intestines of gallstones patients with hypertension, non-alcoholic fatty liver disease, or patients with elevated BMI (≧24). The structure of gut microbiota in patients with gallstones changed significantly, and this might be related to the occurrence of gallstones, rather than metabolic factors such as hypertension, non-alcoholic fatty liver disease, and obesity.
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Affiliation(s)
- Sen-Tao Song
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ling-Yan Cai
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- *Correspondence: Xin Zeng,
| | - Wei-Fen Xie
- Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
- Wei-Fen Xie,
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22
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Biliary Diseases from the Microbiome Perspective: How Microorganisms Could Change the Approach to Benign and Malignant Diseases. Microorganisms 2022; 10:microorganisms10020312. [PMID: 35208765 PMCID: PMC8877314 DOI: 10.3390/microorganisms10020312] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/23/2022] [Accepted: 01/24/2022] [Indexed: 11/18/2022] Open
Abstract
Recent evidence regarding microbiota is modifying the cornerstones on pathogenesis and the approaches to several gastrointestinal diseases, including biliary diseases. The burden of biliary diseases, indeed, is progressively increasing, considering that gallstone disease affects up to 20% of the European population. At the same time, neoplasms of the biliary system have an increasing incidence and poor prognosis. Framing the specific state of biliary eubiosis or dysbiosis is made difficult by the use of heterogeneous techniques and the sometimes unwarranted invasive sampling in healthy subjects. The influence of the microbial balance on the health status of the biliary tract could also account for some of the complications surrounding the post-liver-transplant phase. The aim of this extensive narrative review is to summarize the current evidence on this topic, to highlight gaps in the available evidence in order to guide further clinical research in these settings, and, eventually, to provide new tools to treat biliary lithiasis, biliopancreatic cancers, and even cholestatic disease.
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23
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Hao M, Dou Z, Xu L, Shao Z, Sun H, Li Z. RNA Sequencing Analysis of Gene Expression by Electroacupuncture in Guinea Pig Gallstone Models. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:3793946. [PMID: 35035504 PMCID: PMC8759925 DOI: 10.1155/2022/3793946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/14/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Clinical studies have shown that electroacupuncture (EA) promotes gallbladder motility and alleviates gallstone. However, the mechanism underlying the effects of EA on gallstone is poorly understood. In this study, the mRNA transcriptome analysis was used to study the possible therapeutic targets of EA. METHODS Hartley SPF guinea pigs were employed for the gallstone models. Illumina NovaSeq 6000 platform was used for the RNA sequencing of guinea pig gallbladders in the normal group (Normal), gallstone model group (Model), and EA-treated group (EA). Differently expressed genes (DEGs) were examined separately in Model vs. Normal and EA vs. Model. DEGs reversed by EA were selected by comparing the DEGs of Model vs. Normal and EA vs. Model. Biological functions were enriched by gene ontology (GO) analysis. The protein-protein interaction (PPI) network was analyzed. RESULTS After 2 weeks of EA, 257 DEGs in Model vs. Normal and 1704 DEGs in EA vs. Model were identified. 94 DEGs reversed by EA were identified among these DEGs, including 28 reversed upregulated DEGs and 66 reversed downregulated DEGs. By PPI network analysis, 10 hub genes were found by Cytohubba plugin of Cytoscape. Quantitative real-time PCR (qRT-PCR) verified the changes. CONCLUSION We identified a few GOs and genes that might play key roles in the treatment of gallstone. This study may help understand the therapeutic mechanism of EA for gallstone.
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Affiliation(s)
- Mingyao Hao
- External Treatment Center of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Zhiqiang Dou
- College of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Luyao Xu
- College of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Zongchen Shao
- College of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Hongwei Sun
- Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Zhaofeng Li
- College of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
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24
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Center SA, Randolph JF, Warner KL, McDonough SP, Lucy JM, Sapa KC. Bacterial culture and immunohistochemical detection of bacteria and endotoxin in cats with suppurative cholangitis-cholangiohepatitis syndrome. J Am Vet Med Assoc 2021; 260:194-211. [PMID: 34936576 DOI: 10.2460/javma.20.10.0552] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To characterize the frequency and type of bacterial infection by culture- and immunohistochemical (IHC)-based methods and determine the impact of infection on clinical features and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS 168 client-owned cats with S-CCHS (cases). PROCEDURES Clinical features, bacterial culture results, culture-inoculate sources, and survival details were recorded. Cases were subcategorized by comorbidity (extrahepatic bile duct obstruction, cholelithiasis, cholecystitis, ductal plate malformation, biopsy-confirmed inflammatory bowel disease, and biopsy-confirmed pancreatitis) or treatment by cholecystectomy or cholecystoenterostomy. Culture results, bacterial isolates, Gram-stain characteristics, and IHC staining were compared among comorbidities. Lipoteichoic acid IHC staining detected gram-positive bacterial cell wall components, and toll-like receptor expression IHC reflected pathologic endotoxin (gram-negative bacteria) exposure. RESULTS Clinical features were similar among cases except for more frequent abdominal pain and lethargy in cats with positive culture results and pyrexia, abdominal pain, and hepatomegaly for cats with polymicrobial infections. Bacteria were cultured in 93 of 135 (69%) cats, with common isolates including Enterococcus spp and Escherichia coli. IHC staining was positive in 142 of 151 (94%) cats (lipoteichoic acid, 107/142 [75%]; toll-like receptor 4, 99/142 [70%]). With in-parallel interpretation of culture and IHC-based bacterial detection, 154 of 166 (93%) cats had bacterial infections (gram-positive, 118/154 [77%]; gram-negative, 111/154 [72%]; polymicrobial, 79/154 [51%]). Greater frequency of bacterial isolation occurred with combined tissue, bile, and crushed cholelith inoculates. Infection and gram-positive bacterial isolates were associated with significantly shorter long-term survival times. CLINICAL RELEVANCE S-CCHS was associated with bacterial infection, pathologic endotoxin exposure, and frequent polymicrobial infection in cats. Combined tissue inoculates improved culture detection of associated bacteria.
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Affiliation(s)
- Sharon A Center
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
| | - John F Randolph
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
| | - Karen L Warner
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
| | - Sean P McDonough
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
| | | | - Kirk C Sapa
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
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25
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Rao B, Ren T, Wang X, Wang H, Zou Y, Sun Y, Liu S, Ren Z, Yu Z. Dysbiosis in the Human Microbiome of Cholangiocarcinoma. Front Physiol 2021; 12:715536. [PMID: 34867436 PMCID: PMC8633309 DOI: 10.3389/fphys.2021.715536] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/18/2021] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the most common malignant tumor of the biliary system with a very poor prognosis. The human microbiome, which is the sum of the genetic information of human microorganisms, plays an important role in regulating the digestion, absorption, immune response, and metabolism of the host. Increasing evidence indicates a close relationship between CCA and the human microbiome. Specific alterations occur in the human microbiome of patients with CCA. Therefore, in this review, we aimed to summarize the recent evidence on dysbiosis in the human microbiome of CCA. Then, we generalized the effect of Helicobacter pylori on CCA. Additionally, the potential mechanism of human microbial dysbiosis promoted the progress of CCA, and its precancerous disease was also explored. Furthermore, the possibility of the human microbiome as a diagnostic and therapeutic target of CCA was discussed.
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Affiliation(s)
- Benchen Rao
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tong Ren
- Department of Breast Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuemei Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haiyu Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yawen Zou
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ying Sun
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shanshuo Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhigang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zujiang Yu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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26
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Parra-Landazury NM, Cordova-Gallardo J, Méndez-Sánchez N. Obesity and Gallstones. Visc Med 2021; 37:394-402. [PMID: 34722722 PMCID: PMC8543292 DOI: 10.1159/000515545] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 02/23/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The prevalence of obesity has been increasing globally and represents the main risk factor for the development of gallstone disease (GD). SUMMARY Excess body weight represents the main cause for the development of GD; nevertheless, there have been described multiple risk factors for its development, among them modifiable risk factors as diet, lifestyle, physical inactivity, and non-modifiable risk factors as ethnicity, female sex, advanced age, parity, and genetic mutations. Body mass index, abdominal perimeter, and waist-hip index have been used to determine the degree of adiposity of a person. Hence, central abdominal fat has been mostly associated with insulin resistance with the consequent increase in the hepatic cholesterol secretion; contributing as one of the multiple mechanisms associated with the development of gallstones. This disease has a low mortality; however, it has been associated with multiple diseases such as cardiovascular diseases, carotid atherosclerosis, metabolic associated fatty liver disease, and gallbladder cancer, probably because they share many of the risk factors. KEY MESSAGES GD continues to be considered a disease with a high medical burden, in which it is sought to intervene in modifiable risk factors to reduce its development.
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Affiliation(s)
| | - Jacqueline Cordova-Gallardo
- Department of Hepatology, Service of Surgery and Obesity Clinic, General Hospital “Dr. Manuel Gea González”, Mexico City, Mexico
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Nahum Méndez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
- Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico
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27
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Ploszaj T, Brauncajs M, Traczyk-Borszynska M, Matyjas T, Pomorski L, Wasiak T, Borowiec M. The value of bacterial metagenomic analysis in post-surgical examination of gallstones. Arch Microbiol 2021; 203:6323-6328. [PMID: 34562145 PMCID: PMC8590668 DOI: 10.1007/s00203-021-02580-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 09/14/2021] [Accepted: 09/15/2021] [Indexed: 01/13/2023]
Abstract
Gallstone disease is one of the most common causes of hospitalization for gastrointestinal diseases in the world. Recent studies have examined the presence of bacteria in the formation of stones. Our main goal was to determine the overall composition of gallstone microflora. Gallstones were obtained from 24 patients during laparoscopic cholecystectomy from which DNA were extracted. Composition of bacterial flora was evaluated on 16 s rDNA sequencing technique. In the vast majority of samples, bacteria were present, and four groups could be differentiated regarding the flora. Overall composition shows that 87% of the stones were cholesterol/mixed type of gallstone. Additionally, potentially harmful microorganisms (Streptococcus, Clostridium and Kocuria) that could cause post-surgery complications were identified in several patients. The obtained results indicate that this technique may be useful in analyzing the type of stones and in pinpointing the presence of pathogenic bacteria.
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Affiliation(s)
- T Ploszaj
- Department of Clinical Genetics, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland.
| | - M Brauncajs
- Department of Microbiology and Medical Laboratory Immunology, Medical University of Lodz, Pomorska 251, 92-231, Lodz, Poland
| | - M Traczyk-Borszynska
- Department of Clinical Genetics, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland
| | - T Matyjas
- Department of General and Oncological Surgery, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland
| | - L Pomorski
- Department of General and Oncological Surgery, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland
| | - T Wasiak
- Department of Molecular Biology, Medical University of Lodz, Narutowicza 60, 90-136, Łódź, Poland
| | - M Borowiec
- Department of Clinical Genetics, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland
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28
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Han J, Wu S, Fan Y, Tian Y, Kong J. Biliary Microbiota in Choledocholithiasis and Correlation With Duodenal Microbiota. Front Cell Infect Microbiol 2021; 11:625589. [PMID: 33996618 PMCID: PMC8116743 DOI: 10.3389/fcimb.2021.625589] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 04/12/2021] [Indexed: 12/15/2022] Open
Abstract
Background The pathogenesis of choledocholithiasis is closely related to the role of bacteria. However, little is known about the predictive role of bile bacteria in clinical conditions of patients and the compositional and functional characteristics of biliary microbiota in choledocholithiasis. Methods To investigate the predictive value of biliary bacteria, clinical data of 488 patients with choledocholithiasis were collected. The predictive value of common bile bacteria to patients’ clinical conditions was analyzed by logistic regression. Samples of bile and corresponding duodenal juice from 10 selected patients with choledocholithiasis were obtained, and the composition and function of microbial communities were analyzed based on 16S rRNA sequencing and Tax4Fun. Results The clinical conditions of patients with choledocholithiasis, such as recurrence, the severity of acute cholangitis, and duration of hospital stay were closely related to different species of bile bacteria as well as antimicrobial-resistant bacteria. Employing 16S rRNA sequencing, the dominant phyla of biliary and duodenal microbiota were Proteobacteria and Firmicutes. The top three core microbiota at the genus level were Escherichia–Shigella, Fusobacterium, and Enterococcus. Escherichia coli accounted for the most abundant annotated species in both. Differences in composition between biliary and duodenal microbiota were not significant according to the alpha and beta diversities. Differential abundant features were not found in biliary microbiota indicated by A linear discriminant analysis effective size algorithm. The major pathways identified in biliary and duodenal microbiota were related to membrane transport, translation, replication and repair, carbohydrate and amino acid metabolism. However, no significant difference in those major pathways, as well as antimicrobial-resistance patterns, was observed between biliary and duodenal microbiota. Conclusion Our study first demonstrates the predictive contribution of biliary bacteria to the clinical conditions of patients with choledocholithiasis, and then it offers new insights into the compositional and functional features of biliary and duodenal microbiota. Similarities between biliary and duodenal microbiota support the theory of bacterial duodenal–biliary reflux in patients with choledocholithiasis. Meanwhile, when it is impracticable to obtain a bile sample, duodenal juice may be used as an alternative for bacterial culture and susceptibility tests.
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Affiliation(s)
- Jinyan Han
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shuodong Wu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ying Fan
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu Tian
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jing Kong
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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29
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Hu FL, Chen HT, Guo FF, Yang M, Jiang X, Yu JH, Zhang FM, Xu GQ. Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones. Hepatobiliary Pancreat Dis Int 2021; 20:61-66. [PMID: 33341401 DOI: 10.1016/j.hbpd.2020.12.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 11/11/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis. METHODS Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression. RESULTS A total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.20 ± 1.50 vs. 109.40 ± 3.84 HU, P < 0.0001). Compared to the isodense group, the calcified group showed a higher abundance of gram-positive bacteria at the fundus, in the body and neck of gallbladder tissues. The concentrations of MUC1, MUC2, MUC3a, MUC3b, MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups, while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus (15.49 ± 0.69 vs. 10.23 ± 0.54 ng/mL, P < 0.05), in the body (14.54 ± 0.94 vs. 11.87 ± 0.85 ng/mL, P < 0.05) as well as in the neck (14.77 ± 1.04 vs. 10.85 ± 0.72 ng/mL, P < 0.05) of gallbladder tissues. Moreover, the abundance of bacteria was positively correlated with the expression of MUC4 (r = 0.569, P < 0.05) in the calcified group. CONCLUSIONS This study showed the potential clinical relevance among biliary microbiota, mucins and calcified gallstones in patients with gallstones. Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.
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Affiliation(s)
- Feng-Ling Hu
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hong-Tan Chen
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Fang-Fang Guo
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Ming Yang
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xin Jiang
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jing-Hua Yu
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Fen-Ming Zhang
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Guo-Qiang Xu
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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30
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Shen H, Zhu J, Ye F, Xu D, Fang L, Yang J, Lv H, Lou Q, Jin H, Ni M, Zhang X. Biliary Microbial Structure of Gallstone Patients With a History of Endoscopic Sphincterotomy Surgery. Front Cell Infect Microbiol 2021; 10:594778. [PMID: 33585269 PMCID: PMC7873689 DOI: 10.3389/fcimb.2020.594778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 12/09/2020] [Indexed: 11/13/2022] Open
Abstract
The biliary microbiota is related to the pathogenesis of human bile duct stones. However, the extent to which a history of invasive endoscopic sphincterotomy (EST) affects the biliary bacterial community remains largely unknown. We collected bile samples from the common bile duct of 100 choledocholithiasis patients. We performed 16S rRNA sequencing to investigate and compare the biliary microbial community. The patients without antibiotic treatment (AT) were grouped into three clusters based on their biliary microbial compositions. The patients with a history of EST were significantly enriched in one cluster mainly consisting of gastrointestinal bacteria compared with the other two clusters consisting of oral and environmental bacteria. The β-diversities of patients with and without EST were also significantly different, whereas the α-diversities were comparable. The only significantly enriched bacterial genus associated with a history of EST was Pyramidobacter, while eight other genera were significantly decreased. For patients with AT, seven of these genera maintained their association with EST, including Pyramidobacter. However, after AT, the difference in β-diversities was diminished. EST induced a marked shift in the biliary microbial composition. A cluster of biliary bacteria was associated with a history of EST, and Pyramidobacter was specific to EST.
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Affiliation(s)
- Hongzhang Shen
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Juanjuan Zhu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Fuqiang Ye
- Department of Disease Control and Prevention, Center for Disease Control and Prevention of Eastern Theater Command, Nanjing, China
| | - Dongchao Xu
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liangliang Fang
- The First School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Jianfeng Yang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Huijie Lv
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qifeng Lou
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hangbin Jin
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ming Ni
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Xiaofeng Zhang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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31
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Wang L, Chen J, Jiang W, Cen L, Pan J, Yu C, Li Y, Chen W, Chen C, Shen Z. The Relationship between Helicobacter pylori Infection of the Gallbladder and Chronic Cholecystitis and Cholelithiasis: A Systematic Review and Meta-Analysis. Can J Gastroenterol Hepatol 2021; 2021:8886085. [PMID: 33505946 PMCID: PMC7806380 DOI: 10.1155/2021/8886085] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 11/04/2020] [Accepted: 11/28/2020] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is proved to be the main pathogenic agent of various diseases, including chronic gastritis, gastric ulcer, duodenal ulcer, and gastric cancer. In addition, chronic cholecystitis and cholelithiasis are common worldwide, which are supposed to increase the total mortality of patients. Epidemiologic evidence on the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis still remains unclear. We conducted a systematic review and meta-analysis of overall studies to investigate the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis. Two researchers searched PubMed, Embase, and Cochrane Library databases to obtain all related and eligible studies published before July 2020. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by the random-effects model. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also conducted. Twenty studies were included in the meta-analysis, involving 1735 participants and 1197 patients with chronic cholecystitis/cholelithiasis. Helicobacter species infection of the gallbladder was positively correlated with increased risk of chronic cholecystitis and cholelithiasis, especially H. pylori (OR = 3.05; 95% CI, 1.81-5.14; I 2 = 23.5%). Besides, country-based subgroup analysis also showed a positive correlation between the gallbladder H. pylori positivity and chronic cholecystitis/cholelithiasis risk. For Asian and non-Asian country studies, the ORs were 4.30 (95% CI, 1.76-10.50; I 2 = 37.4%) and 2.13 (95% CI, 1.23-3.70; I 2 = 0.0%), respectively. The association was more obvious using the bile sample and urease gene primer. In conclusion, this meta-analysis provided evidence that there is a positive correlation between H. pylori infection in the gallbladder and increased risk of chronic cholecystitis and cholelithiasis.
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Affiliation(s)
- Liang Wang
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Endoscopy Center, Cangzhou Central Hospital of Hebei Province, Cangzhou, Hebei Province, China
| | - Junyin Chen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Gastroenterology, The Affiliated Hospital, Shaoxing College of Arts and Sciences, Shaoxing, Zhejiang Province, China
| | - Wenxi Jiang
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Li Cen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiaqi Pan
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Weixing Chen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chunxiao Chen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Grigor’eva IN, Romanova TI. Gallstone Disease and Microbiome. Microorganisms 2020; 8:E835. [PMID: 32498344 PMCID: PMC7356158 DOI: 10.3390/microorganisms8060835] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/28/2020] [Accepted: 05/30/2020] [Indexed: 12/12/2022] Open
Abstract
Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out-both in humans and in animal models-confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. The microbiome of bile correlates with the bacterial composition of saliva, and the microbiome of the biliary tract has a high similarity with the microbiota of the duodenum. Pathogenic microflora of the oral cavity, through mechanisms of immunomodulation, can affect the motility of the gallbladder and the expression of mucin genes (MUC1, Muc3, MUC4), and represent one of the promoters of stone formation in the gallbladder. The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. Intestinal bacteria (Clostridium, Bifidobacterium, Peptostreptococcus, Bacteroides, Eubacterium, and Escherichia coli) participating in the oxidation and epimerization of bile acids can disrupt enterohepatic circulation and lead to the formation of gallstones. At the same time, cholecystectomy due to GSD leads to the further transformation of the composition of the microbiota in various parts of the gastrointestinal tract, increasing the risk of developing stomach cancer and colorectal cancer. Further research is required to determine the possibility of using the evaluation of the composition of the microbiota of the gastrointestinal and biliary tracts as an early diagnostic marker of various gastroenterological diseases.
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Affiliation(s)
| | - Tatyana I. Romanova
- Laboratory of Gastroenterology, Research Institute of Internal and Preventive Medicine-Branch of The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia;
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