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Luo X, Ma R, Cai H, Su X, Wang S, Qiao T. Formation of non-cholesterol gallstones in populations within clonorchiasis endemic regions is closely related to Clonorchis sinensis infection. BMC Gastroenterol 2025; 25:345. [PMID: 40340656 PMCID: PMC12060310 DOI: 10.1186/s12876-025-03939-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 04/25/2025] [Indexed: 05/10/2025] Open
Abstract
BACKGROUND Numerous risk factors are linked to gallbladder stone disease (GBSD). Nonetheless, the relationship between Clonorchis sinensis (C. sinensis) and this condition remains to be clarified. METHODS The antibody against C. sinensis in serum and the glucose, triglyceride, and cholesterol levels were investigated in 220 patients with GBSD and 251 controls. Bile components were analysed in patients with gallbladder polyps (GP, n = 18), gallstones (GS, n = 265), and GS combined with C. sinensis infection (GSI, n = 243). Additionally, the gallbladder ejection fraction (%E), residual gallbladder volume (RGV) at 1 h after a fatty meal, and fasting gallbladder volume (FGV) were compared among the GP (n = 43), GS (n = 311), and GSI (n = 277) groups. RESULTS The results indicated positive antibody against C. sinensis (OR: 1.759, 95% CI: 1.163-2.662) and hyperglycaemia (glucose concentration ≥ 6.10 mmol/L, OR: 2.263, 95% CI: 1.227-4.172) were risk factors for GBSD. There were more non-cholesterol stones in GSI patients (216/241, 89.6%) than in GS patients (137/281, 48.8%) (P < 0.0001). Microscopic observations revealed that mucus containing glycogen coated the C. sinensis eggs and the proportion of dead eggs gradually increased in bile, sediment, and stones alongside rising calcium salt content. Total bile acid and cholesterol concentrations were lower in GSI patients than in GP patients or GS patients (P < 0.05). Moreover, increased FGV and RGV and decreased %E were observed in GSI patients compared with GP patients (P < 0.001). CONCLUSIONS The formation of non-cholesterol gallstones in populations residing in endemic areas is related to the deposition, death, and calcification of eggs in the gallbladder, changes in bile components, and decreased gallbladder motility caused by C. sinensis infection.
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Affiliation(s)
- Xiaobing Luo
- Department of Clinical Laboratory, Guangzhou Nansha People's Hospital, No. 7 Xingye Road, Dagang Town, Nansha District, Guangzhou, Guangdong, China.
| | - Ruihong Ma
- Department of Clinical Laboratory, Guangzhou Nansha People's Hospital, No. 7 Xingye Road, Dagang Town, Nansha District, Guangzhou, Guangdong, China
| | - Hongying Cai
- Department of Pathology, Guangzhou Nansha People's Hospital, No. 7 Xingye Road, Dagang Town, Nansha District, Guangzhou, Guangdong, China
| | - Xiangyu Su
- Department of Clinical Laboratory, Guangzhou Nansha People's Hospital, No. 7 Xingye Road, Dagang Town, Nansha District, Guangzhou, Guangdong, China
| | - Sangui Wang
- Dongguan Nancheng Hospital, No. 55 Nancheng Avenue, Guantai Road, Dongguan, Guangdong, China.
| | - Tie Qiao
- The Second People's Hospital of Guangzhou Panyu District, No. 88 Gangdong Road, Dashi Street, Panyu District, Guangzhou, Guangdong, China.
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Yao SY, Li XM, Cai T, Li Y, Liang LX, Liu XM, Lei YF, Zhu Y, Wang F. Helicobacter pylori infection is associated with the risk and phenotypes of cholelithiasis: A multi-center study and meta-analysis. World J Gastroenterol 2024; 30:4991-5006. [PMID: 39713162 PMCID: PMC11612862 DOI: 10.3748/wjg.v30.i47.4991] [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: 07/20/2024] [Revised: 09/05/2024] [Accepted: 09/23/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a prevalent pathogen associated with various diseases. Cholelithiasis is also a common condition. H. pylori infection has been identified in the biliary system, suggesting its potential involvement in biliary diseases. However, the specific role of H. pylori in the development of cholelithiasis remains inconclusive. AIM To investigate the potential association between H. pylori infection and the development of cholelithiasis. METHODS We performed a retrospective study in more than 70000 subjects in health examination center from 3 institutions in the middle, northern and eastern China, from October 2018 to December 2021, to explore the potential association between H. pylori and cholelithiasis through univariate and multivariate analysis. Meanwhile, the influence of H. pylori on biliary-related parameters was investigated. A comprehensive analysis of previous studies concerned about H. pylori and cholelithiasis was also executed. RESULTS In our multi-center study, H. pylori was positively associated with cholelithiasis [odds ratio (OR) = 1.103, 95% confidence interval (CI): 1.001-1.216, P = 0.049]. Furthermore, H. pylori patients had less total and direct bilirubin than uninfected patients, while the total cholesterol and low-density lipoprotein cholesterol were more in H. pylori-positive participants (P < 0.05). In the published articles, the cohort studies indicated H. pylori was a risk factor of cholelithiasis (hazard ratio =1.3280, 95%CI: 1.1810-1.4933, P < 0.0001). The pooled results of case-control and cross-sectional studies showed positive association between H. pylori and cholelithiasis in Asia (OR = 1.5993, 95%CI: 1.0353-2.4706, P = 0.034) but not in Europe (OR = 1.2770, 95%CI: 0.8446-1.9308, P = 0.246). Besides, H. pylori was related to a higher choledocholithiasis/cholecystolithiasis ratio (OR = 3.3215, 95%CI: 1.1034-9.9986, P = 0.033). CONCLUSION H. pylori is positively correlated with cholelithiasis, choledocholithiasis phenotype particularly, especially in Asia, which may be relevant to bilirubin/cholesterol metabolism. Cohort studies confirm an increased risk of cholelithiasis in H. pylori patients.
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Affiliation(s)
- Shuo-Yi Yao
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Xin-Meng Li
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Ting Cai
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Ying Li
- Health Management Center, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Lun-Xi Liang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Xiao-Ming Liu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Yu-Feng Lei
- Department of Gastroenterology, Shanxi Coal Central Hospital, Taiyuan 030006, Shanxi Province, China
| | - Yong Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
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Wang D, Ye A, Jiang N. The role of bacteria in gallstone formation. Folia Microbiol (Praha) 2024; 69:33-40. [PMID: 38252338 DOI: 10.1007/s12223-024-01131-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 12/27/2023] [Indexed: 01/23/2024]
Abstract
Gallstones are a prevalent biliary system disorder that is particularly common in women. They can lead to various complications, such as biliary colic, infection, cholecystitis, and even gallbladder cancer. However, the etiology of gallstones remains incompletely understood. The significant role of bacteria in gallstone formation has been demonstrated in recent studies. Certain bacteria not only influence bile composition and the gallbladder environment but also actively participate in stone formation by producing enzymes such as β-glucuronidase and mucus. Therefore, this review aimed to analyze the mechanisms involving the types and quantities of bacteria involved in gallstone formation, providing valuable references for understanding the etiology and clinical treatment of gallstones.
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Affiliation(s)
- Danfeng Wang
- Health Management (Physical Examination) Section of Hubei Third People's Hospital Affiliated to Jianghan University, Wuhan, 430034, People's Republic of China
| | - Aihui Ye
- Wuchang District Shouyilu Street Community Health Service Center, Wuhan, 430061, People's Republic of China
| | - Ni Jiang
- Health Management (Physical Examination) Section of Hubei Third People's Hospital Affiliated to Jianghan University, Wuhan, 430034, People's Republic of China.
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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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Hirata BHN, Sasagawa S, Navarini A, Mateus HC, Pacheco Junior AM, Salles MJC. Comparison of bacterial profile of gallbladder with gallstones from patients undergoing cholecystectomy due to complicated and uncomplicated cholelithiasis: changes in the epidemiological scenario. Rev Col Bras Cir 2023; 50:e20233474. [PMID: 37162041 PMCID: PMC10508671 DOI: 10.1590/0100-6991e-20233474-en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 02/07/2023] [Indexed: 05/11/2023] Open
Abstract
INTRODUCTION cholelithiasis is a highly prevalent disease of the digestive system in the world. In Brazil, it is a routine condition, whose studies suggest a prevalence of around 10% of adults. Colonization of bile and gallstone pathogens can occur when there is bacterial stasis and proliferation. This proliferation is facilitated by the adhesion and biofilm formation capacity of some bacteria. There are also lithogenic processes that involve bacterial participation. Studies have shown changes in the microbiota of the gallbladder of patients undergoing cholecystectomy, which may impact empirical treatment with antibiotics. METHODOLOGY microbiological analyzes of the sonication fluid of the gallstones and of two samples with bile were performed. Identification and antimicrobial susceptibility testing were performed according to a standard routine. RESULTS of the 34 patients, 76.4% were female. The age group was 48 years +/- 16.61. Acute cholecystitis occurred in 50% of cases. Bactobilia was evidenced in 32.1% of the cases. Klebisiella pneumoniae was noted as the most prevalent pathogen in acute cholecystitis; and Enterobacter sp, in cases of uncomplicated cholelithiasis. Greater sensitivity was obtained in the search for microorganisms in the sonication fluid samples of the stones in relation to the bile samples (p=0.0058). CONCLUSION there was a higher prevalence of bactobilia in patients with acute cholecystitis compared to those with uncomplicated cholelithiasis. The use of sonication in bacterial investigation proved to be superior to the conventional method and can be considered.
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Affiliation(s)
| | - Suzethe Sasagawa
- - Faculdade de Ciências Médicas da Santa Casa de São Paulo, Departamento de Microbiologia - São Paulo - SP - Brasil
| | - Alessandra Navarini
- - Faculdade de Ciências Médicas da Santa Casa de São Paulo, Departamento de Microbiologia - São Paulo - SP - Brasil
| | - Henrique Cunha Mateus
- - Hospital de Misericórdia da Santa Casa de São Paulo, Cirurgia - São Paulo - SP - Brasil
| | | | - Mauro José Costa Salles
- - Hospital de Misericórdia da Santa Casa de São Paulo, Infectologia - São Paulo - SP - Brasil
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Hu J, Tang J, Zhang X, Yang K, Zhong A, Yang Q, Liu Y, Li Y, Zhang T. Landscape in the gallbladder mycobiome and bacteriome of patients undergoing cholelithiasis with chronic cholecystitis. Front Microbiol 2023; 14:1131694. [PMID: 37032855 PMCID: PMC10073429 DOI: 10.3389/fmicb.2023.1131694] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 03/03/2023] [Indexed: 04/11/2023] Open
Abstract
Gallstone disease (GSD) is associated with changes in the gut and gallbladder bacterial composition, but there is limited information on the role of the fungal community (mycobiome) in disease development. This study aimed to characterize the gallbladder mycobiome profiles and their interactions with bacteriome in GSD. A total of 136 bile and gallstone samples (34 paired for bacteriome, and 33 paired and extra 2 bile samples for mycobiome) were obtained from calculi patients with chronic cholecystitis. Bile and gallstone bacteriome and mycobiome were profiled by 16S and internal transcribed spacer (ITS) rRNA gene sequencing, respectively. Gallbladder bacteriome, mycobiome, and interkingdom and intrakingdom interactions were compared between bile and gallstone. In general, microbial diversity was higher in bile than in gallstone, and distinct microbial community structures were observed among them. Deep Sea Euryarchaeotic Group, Rhodobacteraceae, and Rhodobacterales were microbial biomarkers of bile, while Clostridiales and Eubacterium coprostanoligenes were biomarkers of gallstone. Five fungal taxa, including Colletotrichum, Colletotrichum sublineola, and Epicoccum, were enriched in gallstone. Further ecologic analyses revealed that intensive transkingdom correlations between fungi and bacteria and intrakingdom correlations within them observed in gallstone were significantly decreased in bile. Large and complex fungal communities inhabit the gallbladder of patients with GSD. Gallstone, compared with bile, is characterized by significantly altered bacterial taxonomic composition and strengthened bacterial-bacterial, fungal-fungal, and bacterial-fungal correlations in the gallbladder of patients with GSD.
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Affiliation(s)
- Junqing Hu
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- Medical Research Center, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Jichao Tang
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- General Surgery Day Ward, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Xinpeng Zhang
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- General Surgery Day Ward, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Kaijin Yang
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- General Surgery Day Ward, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Ayan Zhong
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- General Surgery Day Ward, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Qin Yang
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- Section for Hepato-Pancreato-Biliary Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Yanjun Liu
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Yi Li
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- General Surgery Day Ward, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Tongtong Zhang
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
- Medical Research Center, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
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Musiał N, Bogucka A, Tretiakow D, Skorek A, Ryl J, Czaplewska P. Proteomic analysis of sialoliths from calcified, lipid and mixed groups as a source of potential biomarkers of deposit formation in the salivary glands. Clin Proteomics 2023; 20:11. [PMID: 36949424 PMCID: PMC10035263 DOI: 10.1186/s12014-023-09402-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 03/08/2023] [Indexed: 03/24/2023] Open
Abstract
Salivary stones, also known as sialoliths, are formed in a pathological situation in the salivary glands. So far, neither the mechanism of their formation nor the factors predisposing to their formation are known despite several hypotheses. While they do not directly threaten human life, they significantly deteriorate the patient's quality of life. Although this is not a typical research material, attempts are made to apply various analytical tools to characterise sialoliths and search for the biomarkers in their proteomes. In this work, we used mass spectrometry and SWATH-MS qualitative and quantitative analysis to investigate the composition and select proteins that may contribute to solid deposits in the salivary glands. Twenty sialoliths, previously characterized spectroscopically and divided into the following groups: calcified (CAL), lipid (LIP) and mixed (MIX), were used for the study. Proteins unique for each of the groups were found, including: for the CAL group among them, e.g. proteins from the S100 group (S100 A8/A12 and P), mucin 7 (MUC7), keratins (KRT1/2/4/5/13), elastase (ELANE) or stomatin (STOM); proteins for the LIP group-transthyretin (TTR), lactotransferrin (LTF), matrix Gla protein (MPG), submandibular gland androgen-regulated protein 3 (SMR3A); mixed stones had the fewest unique proteins. Bacterial proteins present in sialoliths have also been identified. The analysis of the results indicates the possible role of bacterial infections, disturbances in calcium metabolism and neutrophil extracellular traps (NETs) in the formation of sialoliths.
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Affiliation(s)
- Natalia Musiał
- Intercollegiate Faculty of Biotechnology UG&MUG, University of Gdańsk, Abrahama 58, 80-307, Gdańsk, Poland.
| | - Aleksandra Bogucka
- Intercollegiate Faculty of Biotechnology UG&MUG, University of Gdańsk, Abrahama 58, 80-307, Gdańsk, Poland
- Institute of Biochemistry, Medical Faculty, Justus Liebig University of Giessen, Friedrichstrasse 24, 35392, Giessen, Germany
| | - Dmitry Tretiakow
- Department of Otolaryngology, Faculty of Medicine, Medical University of Gdańsk, Smoluchowskiego 17, 80-214, Gdańsk, Poland
| | - Andrzej Skorek
- Department of Otolaryngology, Faculty of Medicine, Medical University of Gdańsk, Smoluchowskiego 17, 80-214, Gdańsk, Poland
| | - Jacek Ryl
- Division of Electrochemistry and Surface Physical Chemistry, Faculty of Applied Physics and Mathematics, Gdańsk University of Technology, G. Narutowicza 11/12, 80-233, Gdańsk, Poland
| | - Paulina Czaplewska
- Intercollegiate Faculty of Biotechnology UG&MUG, University of Gdańsk, Abrahama 58, 80-307, Gdańsk, Poland.
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Usui M, Yoshii Y, Thiriet-Rupert S, Ghigo JM, Beloin C. Intermittent antibiotic treatment of bacterial biofilms favors the rapid evolution of resistance. Commun Biol 2023; 6:275. [PMID: 36928386 PMCID: PMC10020551 DOI: 10.1038/s42003-023-04601-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 02/16/2023] [Indexed: 03/18/2023] Open
Abstract
Bacterial antibiotic resistance is a global health concern of increasing importance and intensive study. Although biofilms are a common source of infections in clinical settings, little is known about the development of antibiotic resistance within biofilms. Here, we use experimental evolution to compare selection of resistance mutations in planktonic and biofilm Escherichia coli populations exposed to clinically relevant cycles of lethal treatment with the aminoglycoside amikacin. Consistently, mutations in sbmA, encoding an inner membrane peptide transporter, and fusA, encoding the essential elongation factor G, are rapidly selected in biofilms, but not in planktonic cells. This is due to a combination of enhanced mutation rate, increased adhesion capacity and protective biofilm-associated tolerance. These results show that the biofilm environment favors rapid evolution of resistance and provide new insights into the dynamic evolution of antibiotic resistance in biofilms.
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Affiliation(s)
- Masaru Usui
- Laboratory of Food Microbiology and Food Safety, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
- Institut Pasteur, Université de Paris Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, 75015, Paris, France.
| | - Yutaka Yoshii
- Institut Pasteur, Université de Paris Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, 75015, Paris, France
| | - Stanislas Thiriet-Rupert
- Institut Pasteur, Université de Paris Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, 75015, Paris, France
| | - Jean-Marc Ghigo
- Institut Pasteur, Université de Paris Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, 75015, Paris, France
| | - Christophe Beloin
- Institut Pasteur, Université de Paris Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, 75015, Paris, France.
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Jayasoma K, Koralegedara NH, Dharmapala A, Chandrajith R. Microstructural and Geochemical Characterization of Gallstones: Implication for Biomineralization. Biol Trace Elem Res 2022; 200:4891-4902. [PMID: 35089502 DOI: 10.1007/s12011-021-03076-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/19/2021] [Indexed: 11/30/2022]
Abstract
Stone formation in the gallbladder is one of the growing health issues reported throughout the world. However, studies on the characteristics of gallstone in the Sri Lankan community are very limited. Detail investigation of gallstone is important for identifying the causative factors and understanding the formation process. The present study aimed to investigate the compositional and microstructural characteristics of gallstone in Sri Lankan patients. Twenty-three patients who were admitted for cholecystectomies were selected for the study. The socio-demographic information was collected from patients using a structured questionnaire. Stones that were removed from surgeries were analyzed by their microstructural and compositional features using Fourier Transformed Infra-Red Spectrometer (FT-IR) and Inductively Coupled Plasma Mass spectroscopy (ICP-MS), Scanning Electron Microscope (SEM), and polarizing microscope. 44% of stones were the mixed type that comprised mainly cholesterol and bilirubinate and followed by pigment type (30%) that mainly contained bilirubinate. The pure cholesterol stones which comprise only cholesterol are the least abundant type of stones. Calcium is the major element found in stones followed by Cu, Mn, Fe, Mg, Zn, and Ni. Higher content of these elements was found in pigment stones compared to the other types. The core and crust regions of stones were enriched with Ca compared to the middle part. Concentric layers that comprise alternating dark and light color bands were observed in the crust, reflecting the compositional variation in bile during the formation of gallstones. The electron microscope images confirmed lightly stacked cholesterol with plate- and needle-like crystals and irregularly arranged clumps of bilirubinate. The Ca-rich core of gallstone confirmed that the Ca-salt precipitation possibly provided a nucleus for the stone formation.
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Affiliation(s)
- Kushani Jayasoma
- Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka
| | | | - Arinda Dharmapala
- Department of Surgery, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Rohana Chandrajith
- Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka.
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Pop R, Tăbăran AF, Ungur AP, Negoescu A, Cătoi C. Helicobacter Pylori-Induced Gastric Infections: From Pathogenesis to Novel Therapeutic Approaches Using Silver Nanoparticles. Pharmaceutics 2022; 14:pharmaceutics14071463. [PMID: 35890358 PMCID: PMC9318142 DOI: 10.3390/pharmaceutics14071463] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 06/29/2022] [Accepted: 07/11/2022] [Indexed: 02/01/2023] Open
Abstract
Helicobacter pylori is the first formally recognized bacterial carcinogen and the most important single digestive pathogen responsible for the induction of gastroduodenal diseases such as gastritis, peptic ulcer, and, finally, gastric neoplasia. The recently reported high rates of antimicrobial drug resistance hamper the current therapies of H. pylori, with therapeutic failure reaching up to 40% of patients. In this context, new treatment options and strategies are urgently needed, but the successful development of these new therapeutic tools is conditioned by the understanding of the high adaptability of H. pylori to the gastric acidic environment and the complex pathogenic mechanism. Due to several advantages, including good antibacterial efficiency, possible targeted delivery, and long tissular persistence, silver nanoparticles (AgNPs) offer the opportunity of exploring new strategies to improve the H. pylori therapy. A new paradigm in the therapy of H. pylori gastric infections using AgNPs has the potential to overcome the current medical limitations imposed by the H. pylori drug resistance, which is reported for most of the current organic antibiotics employed in the classical therapies. This manuscript provides an extensive overview of the pathology of H. pylori-induced gastritis, gastric cancer, and extradigestive diseases and highlights the possible benefits and limitations of employing AgNPs in the therapeutic strategies against H. pylori infections.
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11
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Nascimento JHFD, Tomaz SC, Souza-Filho BMD, Vieira ATS, Andrade ABD, Gusmão-Cunha A. A POPULATION STUDY ON GENDER AND ETHNICITY DIFFERENCES IN GALLBLADDER DISEASE IN BRAZIL. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2022; 35:e1652. [PMID: 35730881 PMCID: PMC9254611 DOI: 10.1590/0102-672020210002e1652] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 02/03/2022] [Indexed: 01/11/2023]
Abstract
Gallbladder diseases (GBD) are one of the most common medical conditions
requiring surgical intervention, both electively and urgently. It is widely
accepted that sex and ethnic characteristics mighty influence both prevalence
and outcomes.
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Affiliation(s)
| | - Selton Cavalcante Tomaz
- Universidade do Estado da Bahia, Departamento de Ciências da Vida - Salvador - Bahia - Brasil
| | | | | | - André Bouzas de Andrade
- Universidade do Estado da Bahia, Departamento de Ciências da Vida - Salvador - Bahia - Brasil
| | - André Gusmão-Cunha
- Universidade do Estado da Bahia, Departamento de Ciências da Vida - Salvador - Bahia - Brasil.,Universidade Federal da Bahia, Faculdade de Medicina da Bahia - Salvador - Bahia - Brazil
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12
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Center SA, Randolph JF, Warner KL, Flanders JA, Harvey HJ. Clinical features, concurrent disorders, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome. J Am Vet Med Assoc 2021; 260:212-227. [PMID: 34936575 DOI: 10.2460/javma.20.10.0555] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To characterize clinical features, comorbidities, frequency of bacterial isolation, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS 168 client-owned cats with S-CCHS. PROCEDURES Data were prospectively (1980 to 2019) collected regarding clinical features, comorbidities, bacterial infection, illness duration, and treatments. Variables were evaluated for associations with survival time. RESULTS Median age of cats was 10.0 years, with no breed or sex predilection observed. Common clinical features included hyporexia (82%), hyperbilirubinemia (80%), lethargy (80%), vomiting (80%), jaundice (67%), weight loss (54%), and hypoalbuminemia (50%). Comorbidities included extrahepatic bile duct obstruction (53%), cholelithiasis (42%), cholecystitis (40%), and ductal plate malformation (44%) as well as biopsy-confirmed inflammatory bowel disease (60/68 [88%]) and pancreatitis (41/44 [93%]). Bacterial cultures were commonly positive (69%) despite prebiopsy antimicrobial administration in most cats. Of surgically confirmed choleliths, diagnostic imaging identified only 58%. Among 55 cats with "idiopathic pancreatitis," 28 (51%) were documented to have transiting choleliths, and 20 had pancreatic biopsies confirming pancreatitis. Cholelithiasis (with or without bile duct obstruction) and cholecystectomy were associated with survival advantages. Survival disadvantages were found for leukocytosis, ≥ 2-fold increased alkaline phosphatase, and hyperbilirubinemia. Cholecystoenterostomy had no survival impact. Cats with ductal plate malformations were significantly younger at diagnosis and death than other cats. Chronic treatments with antimicrobials, S-adenosylmethionine, and ursodeoxycholic acid were common postbiopsy. CLINICAL RELEVANCE S-CCHS in cats was associated with bacterial infection and various comorbidities and may be confused with pancreatitis. Surgically correctable morbidities (ie, cholecystitis, cholecystocholelithiasis) and cholecystectomy provided a significant survival advantage.
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13
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Foster N, Tang Y, Berchieri A, Geng S, Jiao X, Barrow P. Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know? Pathogens 2021; 10:1299. [PMID: 34684248 PMCID: PMC8537056 DOI: 10.3390/pathogens10101299] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/28/2021] [Accepted: 09/29/2021] [Indexed: 11/17/2022] Open
Abstract
One characteristic of the few Salmonella enterica serovars that produce typhoid-like infections is that disease-free persistent infection can occur for months or years in a small number of individuals post-convalescence. The bacteria continue to be shed intermittently which is a key component of the epidemiology of these infections. Persistent chronic infection occurs despite high levels of circulating specific IgG. We have reviewed the information on the basis for persistence in S. Typhi, S. Dublin, S. Gallinarum, S. Pullorum, S. Abortusovis and also S. Typhimurium in mice as a model of persistence. Persistence appears to occur in macrophages in the spleen and liver with shedding either from the gall bladder and gut or the reproductive tract. The involvement of host genetic background in defining persistence is clear from studies with the mouse but less so with human and poultry infections. There is increasing evidence that the organisms (i) modulate the host response away from the typical Th1-type response normally associated with immune clearance of an acute infection to Th2-type or an anti-inflammatory response, and that (ii) the bacteria modulate transformation of macrophage from M1 to M2 type. The bacterial factors involved in this are not yet fully understood. There are early indications that it might be possible to remodulate the response back towards a Th1 response by using cytokine therapy.
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Affiliation(s)
- Neil Foster
- SRUC Aberdeen Campus, Craibstone Estate, Ferguson Building, Aberdeen AB21 9YA, UK
| | - Ying Tang
- Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518055, China;
| | - Angelo Berchieri
- Departamento de Patologia Veterinária, Faculdade de Ciências Agrárias e Veterinárias, Univ Estadual Paulista, Via de Acesso Paulo Donato Castellane, s/n, 14884-900 Jaboticabal, SP, Brazil;
| | - Shizhong Geng
- Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China; (S.G.); (X.J.)
| | - Xinan Jiao
- Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China; (S.G.); (X.J.)
| | - Paul Barrow
- School of Veterinary Medicine, University of Surrey, Daphne Jackson Road, Guildford GU2 7AL, UK;
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14
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Analysis on Microbial Profiles & Components of Bile in Patients with Recurrent CBD Stones after Endoscopic CBD Stone Removal: A Preliminary Study. J Clin Med 2021; 10:jcm10153303. [PMID: 34362087 PMCID: PMC8347313 DOI: 10.3390/jcm10153303] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/24/2021] [Accepted: 07/24/2021] [Indexed: 12/12/2022] Open
Abstract
Background/Aim: Common bile duct (CBD) stone recurrence after endoscopic treatment is a major concern as a late complication. Biliary bacterial factors and biochemical factors determine the path of gallstone formation. The aim of this preliminary study was to investigate the microbial profile and components of bile in patients with and without recurrent CBD stones after endoscopic CBD stone removal. Methods: Among patients who had undergone an initial endoscopic procedure for the removal of CBD stones and were followed up for >2 years, 11 patients who experienced at least two CBD stone recurrences, six months after endoscopic retrograde cholangiopancreatography (ERCP), were categorized into the recurrence group. Nine patients without CBD recurrence events were matched. Results: Polymicrobial infections are generally seen in all patients who have biliary sphincteroplasty. Microbial richness, measured by the numbers of operational taxonomic units (OTUs), was reduced in the recurrence group. The microbial evenness was also significantly lower than in the non-recurrence group. The overall microbial communities in the recurrence group deviated from the non-recurrence group. Infection with bacteria exhibiting β-glucuronidase activity was more frequent in the recurrence group, but there was no statistical significance. In an analysis of the bile components, the bile acid concentration was higher in the non-recurrence group than in the recurrence group. However, the other metabolites were not significantly different. Conclusions: Microbiota dysbiosis and altered bacterial community assembly in bile duct and decreased bile acid in bile juice were associated with recurrence of bile duct stone.
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15
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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: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [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)
| | - Shuodong Wu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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16
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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: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [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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17
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Ferkingstad E, Oddsson A, Gretarsdottir S, Benonisdottir S, Thorleifsson G, Deaton AM, Jonsson S, Stefansson OA, Norddahl GL, Zink F, Arnadottir GA, Gunnarsson B, Halldorsson GH, Helgadottir A, Jensson BO, Kristjansson RP, Sveinbjornsson G, Sverrisson DA, Masson G, Olafsson I, Eyjolfsson GI, Sigurdardottir O, Holm H, Jonsdottir I, Olafsson S, Steingrimsdottir T, Rafnar T, Bjornsson ES, Thorsteinsdottir U, Gudbjartsson DF, Sulem P, Stefansson K. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. Nat Commun 2018; 9:5101. [PMID: 30504769 PMCID: PMC6269469 DOI: 10.1038/s41467-018-07460-y] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 11/01/2018] [Indexed: 01/07/2023] Open
Abstract
Gallstones are responsible for one of the most common diseases in the Western world and are commonly treated with cholecystectomy. We perform a meta-analysis of two genome-wide association studies of gallstone disease in Iceland and the UK, totaling 27,174 cases and 736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR = 1.36 [1.25-1.49], P = 2.1 × 10-12, MAF = 1%; Val98Ile: OR = 1.15 [1.10-1.20], P = 1.8 × 10-10, MAF = 4%). We demonstrate that lower bile acid transport by ASBT is accompanied by greater risk of gallstone disease and highlight the role of the intestinal compartment of the enterohepatic circulation of bile acids in gallstone disease susceptibility. Additionally, two low frequency missense variants in SERPINA1 and HNF4A and 17 common variants represent novel associations with gallstone disease.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Florian Zink
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland
| | | | | | | | | | | | | | | | | | - Gisli Masson
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland
| | - Isleifur Olafsson
- Department of Clinical Biochemistry, Landspítali University Hospital, Reykjavik, 101, Iceland
| | | | - Olof Sigurdardottir
- Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, 600, Iceland
| | - Hilma Holm
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland
| | - Ingileif Jonsdottir
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland
- Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
- Department of Immunology, Landspitali University Hospital, Reykjavik, 101, Iceland
| | - Sigurdur Olafsson
- Department of Internal Medicine, Landspitali University Hospital, Reykjavik, 101, Iceland
| | - Thora Steingrimsdottir
- Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
- Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, 101, Iceland
| | | | - Einar S Bjornsson
- Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
- Department of Internal Medicine, Landspitali University Hospital, Reykjavik, 101, Iceland
| | - Unnur Thorsteinsdottir
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland
- Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
| | - Daniel F Gudbjartsson
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland
- School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 101, Iceland
| | - Patrick Sulem
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.
| | - Kari Stefansson
- deCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.
- Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
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18
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Kose SH, Grice K, Orsi WD, Ballal M, Coolen MJL. Metagenomics of pigmented and cholesterol gallstones: the putative role of bacteria. Sci Rep 2018; 8:11218. [PMID: 30046045 PMCID: PMC6060111 DOI: 10.1038/s41598-018-29571-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 07/13/2018] [Indexed: 01/10/2023] Open
Abstract
There is growing evidence for bacteria playing a role in the pathogenesis and formation of pigmented gallstones from humans. These studies mainly involved cultivation of gallstone-associated bacteria and 16S rRNA profiling, providing an indirect link between processes involved in gallstone formation by the bacteria in-situ. Here, we provide functional metagenomic evidence of a range of genes involved in bile stress response, biofilm formation, and anaerobic energy metabolism by Gram-negative Klebsiella in pigmented gallstones from a 76-year-old male patient. Klebsiella was also present in one cholesterol-type stone in a 30-year-old female patient who had additional cholesterol gallstones characterised by Gram-positive bacteria. Pigmented stones further revealed a predominance of genes involved in carbohydrate metabolism, whilst cholesterol stones indicated a profile dominanted by protein metabolism possibly reflecting known chemical differences between Gram-negative and Gram-positive biofilm matrices. Archaeal genes were not detected. Complementary carbon and hydrogen isotopic analyses of cholesterol within the patients’ stones revealed homogeneity, suggesting a common diet or cholesterol biosynthesis pathway that has little influence on microbial composition. This pilot study provides a framework to study microbial processes that play a potential role in gallstone formation across markedly different types of stones and patient backgrounds.
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Affiliation(s)
- S H Kose
- School of Molecular and Life Sciences, Curtin University, Perth, WA, 6102, Australia. .,WA-Organic and Isotope Geochemistry Centre, School of Earth and Planetary Science, Curtin University, Perth, WA, 6102, Australia.
| | - K Grice
- WA-Organic and Isotope Geochemistry Centre, School of Earth and Planetary Science, Curtin University, Perth, WA, 6102, Australia
| | - W D Orsi
- Department of Earth and Environmental Science, Paleontology and Geobiology, Ludwig-Maximilians-Universität München, 80333, Munich, Germany.,GeoBio Centre LMU, Ludwig-Maximilians-Universität München, 80333, Munich, Germany
| | - M Ballal
- Fiona Stanley Hospital, 11 Robin Warren Dr, Murdoch, 6150, WA, Australia.,St John of God Murdoch Hospital, Barry Marshall Parade, Murdoch, 6150, WA, Australia
| | - M J L Coolen
- WA-Organic and Isotope Geochemistry Centre, School of Earth and Planetary Science, Curtin University, Perth, WA, 6102, Australia
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19
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Zhou B, Hu J, Zhong Y. Surgical treatments for patients with recurrent bile duct stones and Oddis sphincter laxity. Intractable Rare Dis Res 2017; 6:172-176. [PMID: 28944138 PMCID: PMC5608926 DOI: 10.5582/irdr.2017.01053] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Recurrent bile duct stones is the most common complication after gallstone surgery and the incidence is about 4-24%. Sphincter of Oddi laxity will lead to duodenal content flow into the bile or pancreatic duct. Patients with recurrent bile duct stones and Oddis sphincter laxity were intractable. Here we sought to present the possible and helpful surgical treatments for such patients. Prospective randomized clinical trial are needed for evaluating the outcome of surgical treatments.
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Affiliation(s)
- Boxuan Zhou
- Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jinxiong Hu
- Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yuesi Zhong
- Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- Address correspondence to: Dr. Yuesi Zhong, Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. E-mail:
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20
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Kleinlützum D, Plesker R. A case of gallstones in an African green monkey ( Chlorocebus aethiops). Primate Biol 2017; 4:33-37. [PMID: 32110690 PMCID: PMC7041542 DOI: 10.5194/pb-4-33-2017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 01/02/2017] [Indexed: 01/11/2023] Open
Abstract
Spontaneous cholelithiasis was found in a male African green monkey
(Chlorocebus aethiops) at necropsy. Choleliths varied in size, shape
and colour. Gallstones were analysed using accepted analytical methods. Results
showed that the gallstones were composed of cholesterol and protein in
varying proportions. Histologically, the gallbladder showed diffuse mild to
moderate lymphocytic infiltration. The etiology of the cholelithiasis in the
examined individual remains unknown.
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Affiliation(s)
- Dina Kleinlützum
- Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany
| | - Roland Plesker
- Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany
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21
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Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts. PLoS One 2016; 11:e0150519. [PMID: 26930491 PMCID: PMC4773253 DOI: 10.1371/journal.pone.0150519] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 02/15/2016] [Indexed: 02/08/2023] Open
Abstract
Biliary bacteria have been implicated in gallstone pathogenesis, though a clear understanding of their composition and source is lacking. Moreover, the effects of the biliary environment, which is known to be generally hostile to most bacteria, on biliary bacteria are unclear. Here, we investigated the bacterial communities of the biliary tract, duodenum, stomach, and oral cavity from six gallstone patients by using 16S rRNA amplicon sequencing. We found that all observed biliary bacteria were detectable in the upper digestive tract. The biliary microbiota had a comparatively higher similarity with the duodenal microbiota, versus those of the other regions, but with a reduced diversity. Although the majority of identified bacteria were greatly diminished in bile samples, three Enterobacteriaceae genera (Escherichia, Klebsiella, and an unclassified genus) and Pyramidobacter were abundant in bile. Predictive functional analysis indicated enhanced abilities of environmental information processing and cell motility of biliary bacteria. Our study provides evidence for the potential source of biliary bacteria, and illustrates the influence of the biliary system on biliary bacterial communities.
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22
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Fusconi M, Petrozza V, Schippa S, de Vincentiis M, Familiari G, Pantanella F, Cirenza M, Iebba V, Battaglione E, Greco A, Gallipoli C, Campo F, Gallo A. Bacterial Biofilm in Salivary Gland Stones: Cause or Consequence? Otolaryngol Head Neck Surg 2016; 154:449-53. [PMID: 26759424 DOI: 10.1177/0194599815622425] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 11/24/2015] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The pathogenesis of salivary calculi is not yet clear; however, 2 theories have been formulated: (1) "the classic theory," based on calcium microdeposits in serous and ductal acinous cells, successively discharged into the ducts; (2) "the retrograde theory," based on a retrograde migration of food, bacteria, and so on from the oral cavity to the salivary duct. The aim of the present study is to highlight the role of bacteria and biofilm in stone formation. STUDY DESIGN Case series without comparison. SETTING Laboratory of the Department of Anatomical Pathology. SUBJECTS AND METHODS Traditional optic microscopy and scanning electron microscopy were carried out on 15 salivary gland calculi that were collected from 12 patients. A qPCR (quantitative real-time polymerase chain reaction) assay was performed to highlight the presence of bacterial DNA on each stone. RESULTS Optic microscopy showed formations that-due to their size, shape, and Gram and Giemsa staining-seemed to be Gram-positive bacterial cells. PAS- (periodic acid-Schiff) and alcian-PAS-positive staining matrix was present around them. The ultrastructural observation of the material processed for scanning electron microscopy showed the presence of structures resembling bacterial cells in the middle of the stones, surrounded by soft, amorphous material. Results of qPCR showed the presence of bacterial DNA in the internal part of the tissue sample. CONCLUSIONS The presence of bacteria and/or bacterial products resembling biofilm in salivary gland stones supports the "retrograde theory." This evidence may support the hypothesis that biofilm could be the causative effect of lithiasic formations.
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Affiliation(s)
- Massimo Fusconi
- Department of Sensory Organs, ENT Clinic, Sapienza University of Rome, Rome, Italy
| | - Vincenzo Petrozza
- Department of Medical and Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy
| | - Serena Schippa
- Department of Public Health and Infectious Diseases, Microbiology Section, Sapienza University of Rome, Rome, Italy
| | - Marco de Vincentiis
- Department of Sensory Organs, ENT Clinic, Sapienza University of Rome, Rome, Italy
| | - Giuseppe Familiari
- Department of Anatomical Pathology, Forensic and Locomotor Apparatus Sciences, Sapienza University of Rome, Rome, Italy
| | - Fabrizio Pantanella
- Department of Public Health and Infectious Diseases, Microbiology Section, Sapienza University of Rome, Rome, Italy
| | - Mirko Cirenza
- Department of Medical and Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy
| | - Valerio Iebba
- Department of Public Health and Infectious Diseases, Microbiology Section, Sapienza University of Rome, Rome, Italy
| | - Ezio Battaglione
- Department of Anatomical Pathology, Forensic and Locomotor Apparatus Sciences, Sapienza University of Rome, Rome, Italy
| | - Antonio Greco
- Department of Sensory Organs, ENT Clinic, Sapienza University of Rome, Rome, Italy
| | - Camilla Gallipoli
- Department of Medical-Surgical Biotechnologies and Science, ENT, Sapienza University of Rome, Latina, Italy
| | - Flaminia Campo
- Department of Sensory Organs, ENT Clinic, Sapienza University of Rome, Rome, Italy
| | - Andrea Gallo
- Department of Medical-Surgical Biotechnologies and Science, ENT, Sapienza University of Rome, Latina, Italy
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Shen H, Ye F, Xie L, Yang J, Li Z, Xu P, Meng F, Li L, Chen Y, Bo X, Ni M, Zhang X. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria. Sci Rep 2015; 5:17450. [PMID: 26625708 PMCID: PMC4667190 DOI: 10.1038/srep17450] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 10/29/2015] [Indexed: 02/07/2023] Open
Abstract
Despite the high worldwide prevalence of gallstone disease, the role of the biliary microbiota in gallstone pathogenesis remains obscure. Next-generation sequencing offers advantages for systematically understanding the human microbiota; however, there have been few such investigations of the biliary microbiome. Here, we performed whole-metagenome shotgun (WMS) sequencing and 16S rRNA sequencing on bile samples from 15 Chinese patients with gallstone disease. Microbial communities of most individuals were clustered into two types, according to the relative enrichment of different intestinal bacterial species. In the bile samples, oral cavity/respiratory tract inhabitants were more prevalent than intestinal inhabitants and existed in both community types. Unexpectedly, the two types were not associated with fever status or surgical history, and many bacteria were patient-specific. We identified 13 novel biliary bacteria based on WMS sequencing, as well as genes encoding putative proteins related to gallstone formation and bile resistance (e.g., β-glucuronidase and multidrug efflux pumps). Bile samples from gallstone patients had reduced microbial diversity compared to healthy faecal samples. Patient samples were enriched in pathways related to oxidative stress and flagellar assembly, whereas carbohydrate metabolic pathways showed varying behaviours. As the first biliary WMS survey, our study reveals the complexity and specificity of biliary microecology.
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Affiliation(s)
- Hongzhang Shen
- Department of Gastroenterology, Hangzhou First People's Hospital, Hangzhou 310000, People's Republic of China
| | - Fuqiang Ye
- Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.,Genomics Center of Academy of Military Medical Sciences, Beijing 100850, People's Republic of China
| | - Lu Xie
- Department of Gastroenterology, Hangzhou First People's Hospital, Hangzhou 310000, People's Republic of China
| | - Jianfeng Yang
- Department of Gastroenterology, Hangzhou First People's Hospital, Hangzhou 310000, People's Republic of China
| | - Zhen Li
- Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.,Genomics Center of Academy of Military Medical Sciences, Beijing 100850, People's Republic of China
| | - Peisong Xu
- Department of Research Service, Zhiyuan Inspection Medical Institute, Hangzhou 310009, People's Republic of China
| | - Fei Meng
- Department of Research Service, Zhiyuan Inspection Medical Institute, Hangzhou 310009, People's Republic of China
| | - Lei Li
- Department of Research Service, Zhiyuan Inspection Medical Institute, Hangzhou 310009, People's Republic of China
| | - Ying Chen
- Department of Radiation Toxicology &Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China
| | - Xiaochen Bo
- Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.,Genomics Center of Academy of Military Medical Sciences, Beijing 100850, People's Republic of China
| | - Ming Ni
- Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.,Genomics Center of Academy of Military Medical Sciences, Beijing 100850, People's Republic of China
| | - Xiaofeng Zhang
- Department of Gastroenterology, Hangzhou First People's Hospital, Hangzhou 310000, People's Republic of China
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24
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Abstract
Background Acute bacterial cholangitis for the most part owing to common bile duct stones is common in gastroenterology practice and represents a potentially life-threatening condition often characterized by fever, abdominal pain, and jaundice (Charcot's triad) as well as confusion and septic shock (Reynolds' pentad). Methods This review is based on a systematic literature review in PubMed with the search items ‘cholangitis’, ‘choledocholithiasis’, ‘gallstone disease’, ‘biliary infection’, and ‘biliary sepsis’. Results Although most patients respond to empiric broad-spectrum antibiotic treatment, timely endoscopic biliary drainage depending on the severity of the disease is required to eliminate the underlying obstruction. Specific recommendations have been derived from the Tokyo guideline working group consensus 2006 and its update in 2013, albeit poorly evidence-based, providing a comprehensive overview of diagnosis, classification, risk stratification, and treatment algorithms in acute bacterial cholangitis. Conclusion Prompt clinical recognition and accurate diagnostic workup including adequate laboratory assessment and (aetiology-oriented) imaging are critical steps in the management of cholangitis. Treatment is directed at the two major interrelated pathophysiologic components, i.e. bacterial infection (immediate antimicrobial therapy) and bile duct obstruction (biliary drainage). As for the latter, transpapillary endoscopic drainage by stent or nasobiliary drain and/or same-session bile duct clearance, depending on individual disease severity, represent first-line treatment approaches.
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Affiliation(s)
- Vincent Zimmer
- Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany
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25
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Darkahi B, Sandblom G, Liljeholm H, Videhult P, Melhus Å, Rasmussen IC. Biliary microflora in patients undergoing cholecystectomy. Surg Infect (Larchmt) 2014; 15:262-5. [PMID: 24801654 DOI: 10.1089/sur.2012.125] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The management of acute cholecystitis requires a sound knowledge of the biliary microflora. METHODS Bile samples were taken for culture according to a standard routine during all cholecystectomies performed from April 2007 to February 2009 in the Department of Surgery at Enköping Hospital. The use of antibiotics within the 3-mo period before surgery, indication for surgery, prophylactic antibiotics, and post-operative complications were recorded prospectively. RESULTS Altogether, 246 procedures were performed during the study period, of which 149 (62%) were done on women. The mean (±SD) age of the study subjects was 49±16 y. Bacterial growth was seen in cultures from 34 (14%) of the subjects. The mean age of subjects with positive cultures was 64 y and that of subjects with negative cultures was 47 y (p<0.001). Positive culture was seen in 16 (31%) of the 51 patients who underwent operations for acute cholecystitis, whereas positive cultures were obtained in 18 of 195 patients without acute cholecystitis (9%) (p<0.001). Resistance to ampicillin was recorded in three of 34 (9%) of the cultures with bacterial growth, to co-trimoxazole in one of the 34 (3%) cultures, to fluoroquinolones in one of the 34 (3%) cultures, and to cephalosporins in one of the 34 (3%) cultures. Resistance to piperacillin-tazobactam was not observed in any of the cultures. In multivariable logistic regression analysis, a positive culture was the only factor significantly associated with risk for post-operative infectious complications (p<0.05). DISCUSSION Bacterial growth in the bile is observed more often in patients undergoing surgery for acute cholecystitis. The microflora of the bile is probably important for the outcome of surgery, but further studies are required for assessing the effectiveness of measures for preventing infectious post-operative complications.
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Affiliation(s)
- Bahman Darkahi
- 1 Department of Surgery, Enköping Hospital , Enköping, Sweden
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26
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Identification of Salmonella enterica serovar Typhimurium genes regulated during biofilm formation on cholesterol gallstone surfaces. Infect Immun 2013; 81:3770-80. [PMID: 23897604 DOI: 10.1128/iai.00647-13] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Salmonella spp. are able to form biofilms on abiotic and biotic surfaces. In vivo studies in our laboratory have shown that Salmonella can form biofilms on the surfaces of cholesterol gallstones in the gallbladders of mice and human carriers. Biofilm formation on gallstones has been demonstrated to be a mechanism of persistence. The purpose of this work was to identify and evaluate Salmonella sp. cholesterol-dependent biofilm factors. Differential gene expression analysis between biofilms on glass or cholesterol-coated surfaces and subsequent quantitative real-time PCR (qRT-PCR) revealed that type 1 fimbria structural genes and a gene encoding a putative outer membrane protein (ycfR) were specifically upregulated in Salmonella enterica serovar Typhimurium biofilms grown on cholesterol-coated surfaces. Spatiotemporal expression of ycfR and FimA verified their regulation during biofilm development on cholesterol-coated surfaces. Surprisingly, confocal and scanning electron microscopy demonstrated that a mutant of type 1 fimbria structural genes (ΔfimAICDHF) and a ycfR mutant showed increased biofilm formation on cholesterol-coated surfaces. In vivo experiments using Nramp1(+/+) mice harboring gallstones showed that only the ΔycfR mutant formed extensive biofilms on mouse gallstones at 7 and 21 days postinfection; ΔfimAICDHF was not observed on gallstone surfaces after the 7-day-postinfection time point. These data suggest that in Salmonella spp., wild-type type 1 fimbriae are important for attachment to and/or persistence on gallstones at later points of chronic infection, whereas YcfR may represent a specific potential natural inhibitor of initial biofilm formation on gallstones.
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27
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Abstract
Infections of the gastrointestinal tract can often involve the gallbladder. Infection probably plays a role in the formation of gallstones but is more commonly thought to contribute to acute illness in patients. Acute calculous cholecystitis caused by an impacted gallstone is often complicated by secondary bacterial infection and is a major cause of morbidity and even mortality in patients. A wide variety of organisms can be associated with acute acalculous cholecystitis, a less common but potentially more severe form of acute cholecystitis. This review focuses on infections and their role in the above-mentioned processes involving the gallbladder.
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Affiliation(s)
- Kabir Julka
- Division of Gastroenterology, University of Washington, Seattle, WA 98195, USA
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28
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Gonzalez-Escobedo G, Marshall JM, Gunn JS. Chronic and acute infection of the gall bladder by Salmonella Typhi: understanding the carrier state. Nat Rev Microbiol 2011; 9:9-14. [PMID: 21113180 PMCID: PMC3255095 DOI: 10.1038/nrmicro2490] [Citation(s) in RCA: 210] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Despite major treatment and prevention efforts, millions of new typhoid infections occur worldwide each year. For a subset of infected individuals, Salmonella enterica subsp. enterica serovar Typhi colonizes the gall bladder and remains there long after symptoms subside, serving as a reservoir for the further spread of the disease. In this Progress article, we explore recent advances in our understanding of the mechanisms by which Salmonella spp.--predominantly S. Typhi--colonize and persist in the human gall bladder.
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Affiliation(s)
- Geoffrey Gonzalez-Escobedo
- Center for Microbial Interface Biology and the Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA
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29
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Slingluff JL, Williams JT, Blau L, Blau A, Dick EJ, Hubbard GB. Spontaneous gallbladder pathology in baboons. J Med Primatol 2009; 39:92-6. [PMID: 19793177 DOI: 10.1111/j.1600-0684.2009.00387.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Gallbladder pathology (GBP) is a relatively uncommon, naturally occurring morbidity in both baboons and humans. METHODS A retrospective analysis was performed on 7776 necropsy reports over a 20 year period to determine the prevalence of baboon GBP. RESULTS Ninety-seven cases of GBP were identified, yielding a 20 year population prevalence of 1.25%. GBP is more common in adult female baboons, occurring with a female to male ratio of nearly 2:1. Among gallbladder pathologies, cholecystitis (35.1%) and cholelithiasis (29.9%) were the most prevalent abnormalities, followed by hyperplasia (16.5%), edema (15.5%), amyloidosis (5.2%), fibrosis (4.1%), necrosis (4.1%), and hemorrhage (1.0%). CONCLUSION Many epidemiologic similarities exist between GBP in baboons and humans suggesting that the baboon may serve as a reliable animal model system for investigating GBP in humans.
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Affiliation(s)
- J L Slingluff
- College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA, USA
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30
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Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology 2009; 136:425-40. [PMID: 19109959 PMCID: PMC2774219 DOI: 10.1053/j.gastro.2008.12.031] [Citation(s) in RCA: 124] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2008] [Revised: 12/05/2008] [Accepted: 12/08/2008] [Indexed: 12/12/2022]
Abstract
Cholesterol gallstone formation is a complex process mediated by genetic and environmental factors. Until recently, the role of the immune system in the pathogenesis of cholesterol gallstones was not considered a valid topic of research interest. This review collates and interprets an extensive body of basic literature, some of which is not customarily considered to be related to cholelithogenesis, describing the multiple facets of the immune system that appear to be involved in cholesterol cholelithogenesis. A thorough understanding of the immune interactions with biliary lipids and cholecystocytes should modify current views of the pathogenesis of cholesterol gallstones, promote further research on the pathways involved, and lead to novel diagnostic tools, treatments, and preventive measures.
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Affiliation(s)
- Kirk J Maurer
- Division of Gastroenterology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
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31
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Abstract
We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0–33.4), 8.0 (95% CI 5.6–11.4), and 4.2 (95% CI 2.5–7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9–59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P<0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P=0.001). We estimate that in Shanghai 80% (95% CI 75–84%), 59% (56–61%), and 41% (29–59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones.
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32
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HSING ANNW, RASHID ASIF, DEVESA SUSANS, FRAUMENI JOSEPHF. Biliary Tract Cancer. CANCER EPIDEMIOLOGY AND PREVENTION 2006:787-800. [DOI: 10.1093/acprof:oso/9780195149616.003.0040] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
AbstractThis chapter reviews the epidemiology of biliary tract cancer. Many etiologic leads for biliary tract cancer have come from clinical observations, autopsy series, and descriptive epidemiologic studies. While a significant fraction of these tumors are related to gallstones (cholelithiasis), information on other risk factors is limited, due to the rarity of the tumors, the often rapidly fatal course, and the small number of epidemiologic studies conducted to date. Because the three anatomic categories of biliary tract cancer have distinct epidemiologic patterns and molecular changes, including somatic mutations and loss of heterozygosity (LOH), it has been suggested that the causal factors vary by subsite.
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33
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Puppala S, Dodd GD, Fowler S, Arya R, Schneider J, Farook VS, Granato R, Dyer TD, Almasy L, Jenkinson CP, Diehl AK, Stern MP, Blangero J, Duggirala R. A genomewide search finds major susceptibility loci for gallbladder disease on chromosome 1 in Mexican Americans. Am J Hum Genet 2006; 78:377-92. [PMID: 16400619 PMCID: PMC1380282 DOI: 10.1086/500274] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Accepted: 11/16/2005] [Indexed: 12/11/2022] Open
Abstract
Gallbladder disease (GBD) is one of the major digestive diseases. Its risk factors include age, sex, obesity, type 2 diabetes, and metabolic syndrome (MS). The prevalence of GBD is high in minority populations, such as Native and Mexican Americans. Ethnic differences, familial aggregation of GBD, and the identification of susceptibility loci for gallstone disease by use of animal models suggest genetic influences on GBD. However, the major susceptibility loci for GBD in human populations have not been identified. Using ultrasound-based information on GBD occurrence and a 10-cM gene map, we performed multipoint variance-components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in the San Antonio Family Diabetes/Gallbladder Study were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. With use of the National Cholesterol Education Program/Adult Treatment Panel III criteria, five MS risk factors were defined: increased waist circumference, hypertriglyceredemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The MS risk-factor score (range 0-5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and MS risk-factor score, we found stronger linkage signals for the symptomatic GBD phenotype. The highest LOD scores (3.7 and 3.5) occurred on chromosome 1p between markers D1S1597 and D1S407 (1p36.21) and near marker D1S255 (1p34.3), respectively. Other genetic locations (chromosomes 2p, 3q, 4p, 8p, 9p, 10p, and 16q) across the genome exhibited some evidence of linkage (LOD >or=1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of Lith loci, which influence gallstone formation in mouse models. In conclusion, we found significant evidence of major genetic determinants of symptomatic GBD on chromosome 1p in Mexican Americans.
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Affiliation(s)
- Sobha Puppala
- Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
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Gilloteaux J, Miller D, Morrison RL. Intracellular liposomes and cholesterol deposits in chronic cholecystitis and biliary sludge. Ultrastruct Pathol 2004; 28:123-36. [PMID: 15471425 DOI: 10.1080/01913120490475888] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Ultrastructural study of a group of selected specimens of chronic cholecystitic gallbladders reveals cholecystocyte changes characterized by abraded and altered microvilli accompanied by mitochondrial damages in the apical regions as well as mucus accumulation with aggregated, angulated lysosomes and heterogeneous liposomes. These liposomes contain needle-like crystals, probably rich in cholesterol. Many fragments of cholecystocystes and damaged organelles or contents can be found in the biliary sludge. These data support previous reports suggesting that there is an association between cholecystitis and the presence of cholelithiasis, subsequent to the production of altered bile. The present data suggest that disintegrating, sloughed cholecystocyte contents also contribute to the bile sludge, a complex milieu enriched by lipids, cholesterol deposits, altered mucus due in part to changes in expression of apomucins. The instability of prolonged storage of such modified bile, caused and/or accompanied by other associated metabolic defects, including gallbladder sluggishness, would favor the nucleation and the enlargement of gallstones. Based on the aforementioned data, a comprehensive sequence for cholecystocyte ultrastructural alterations and pathologies is proposed, as a result of chronic cholecystitis.
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Affiliation(s)
- Jacques Gilloteaux
- Departments of Pathology and Surgery, Summa Health System, Summa Research Foundation, Akron, Ohio, USA.
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35
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Sripa B, Kanla P, Sinawat P, Haswell-Elkins MR. Opisthorchiasis-associated biliary stones: Light and scanning electron microscopic study. World J Gastroenterol 2004; 10:3318-21. [PMID: 15484308 PMCID: PMC4572303 DOI: 10.3748/wjg.v10.i22.3318] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: Biliary stones are frequently encountered in areas endemic for opisthorchiasis in Thailand. The present study was to describe the prevalence and pathogenesis of these stones.
METHODS: Gallstones and/or common bile duct stones and bile specimens from 113 consecutive cholecystectomies were included. Bile samples, including sludge and/or microcalculi, were examined for Opisthorchisviverrini eggs, calcium and bilirubin. The stones were also processed for scanning electron microscopic (SEM) study.
RESULTS: Of the 113 cases, 82 had pigment stones, while one had cholesterol stones. The other 30 cases had no stones. Most of the stone cases (76%, 63/83) had multiple stones, while the remainder had a single stone. Stones were more frequently observed in females. Bile examination was positive for O.viverrini eggs in 50% of the cases studied. Aggregates of calcium bilirubinate precipitates were observed in all cases with sludge. Deposition of calcium bilirubinate on the eggshell was visualized by special staining. A SEM study demonstrated the presence of the parasite eggs in the stones. Numerous crystals, morphologically consistent with calcium derivatives and cholesterol precipitates, were seen.
CONCLUSION: Northeast Thailand has a high prevalence of pigment stones, as observed at the cholecystectomy, and liver fluke infestation seems involved in the pathogenesis of stone formation.
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Affiliation(s)
- Banchob Sripa
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
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36
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Ko CW, Lee SP. Gastrointestinal disorders of the critically ill. Biliary sludge and cholecystitis. Best Pract Res Clin Gastroenterol 2003; 17:383-96. [PMID: 12763503 DOI: 10.1016/s1521-6918(03)00026-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Biliary sludge develops commonly in critically ill patients and may be associated with biliary colic, acute pancreatitis or acute cholecystitis. Sludge often resolves upon resolution of the underlying pathogenetic factor. It is generally diagnosed on sonography. Treatment of sludge itself is unnecessary unless further complications develop. Acute acalculous cholecystitis also develops frequently in critically ill patients. It may be difficult to diagnose in these patients, manifesting only as unexplained fever, leukocytosis or sepsis. Sonography and hepatobiliary scintigraphy are the most useful diagnostic tests. Management decisions should take into account the underlying co-morbid conditions. For many patients, percutaneous cholecystostomy may be the best management option. Cholecystostomy may also provide definitive drainage as patients recover and underlying critical illness resolves.
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Affiliation(s)
- Cynthia W Ko
- Division of Gastroenterology, Department of Medicine, University of Washington, Box 356424, Seattle, WA 98195, USA.
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