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Deng YH, Jiang M, Chen Y, Chen HB. Pharmacovigilance analysis of small bowel bleeding associated with NSAIDs. Ther Adv Drug Saf 2025; 16:20420986251318848. [PMID: 40336902 PMCID: PMC12056324 DOI: 10.1177/20420986251318848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 01/21/2025] [Indexed: 05/09/2025] Open
Abstract
Background Currently, the factors influencing small bowel bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remain unclear. Objectives This study aimed to assess NSAID-associated small bowel bleeding and evaluate the impact of other drugs on it through a pharmacovigilance study, thereby providing valuable insights for clinical practice. Design Data on NSAID-associated small bowel bleeding were retrospectively extracted from two public adverse drug reaction databases-the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) and the Japan Pharmaceuticals and Medical Devices Agency's Adverse Drug Event Reporting (JADER)-from 2004 to 2023 for further analysis. Methods The reporting odds ratio (ROR), a pharmacovigilance technique, was employed to identify signals of adverse reactions, and the Chi-square test was utilized to assess differences between groups. Results Multiple NSAIDs associated with small bowel bleeding were identified in both databases. In the drug combination analysis, no significant differences in the risk of small bowel bleeding were found between NSAIDs combined with proton pump inhibitors (PPIs) and NSAIDs alone in FAERS (all p > 0.05). Decreasing risks were found when multiple NSAIDs were combined with rebamipide or probiotics compared to NSAIDs alone in JADER (p < 0.05 and ROR < 1). In subgroup analyses of age and sex, older adults and males who used aspirin showed higher risk signals in both databases (all p < 0.05 and ROR > 1). Conclusion PPIs did not show a significant impact on NSAIDs-associated small bowel bleeding, while rebamipide and probiotics may exhibited a preventive effect against NSAIDs-associated small bowel bleeding. Older adults and males constituted risk factors for aspirin-associated small bowel bleeding.
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Affiliation(s)
- Ying-Han Deng
- Department of Gastroenterology, Sanming First Hospital Affiliated to Fujian Medical University, Sanming, China
| | - Meiting Jiang
- Department of Gastroenterology, Sanming First Hospital Affiliated to Fujian Medical University, Sanming, China
| | - Yun Chen
- Department of Gastroenterology, Sanming First Hospital Affiliated to Fujian Medical University, Sanming, China
| | - Hong-Bin Chen
- Department of Gastroenterology, Sanming First Hospital Affiliated to Fujian Medical University, Sanming 365000, China
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Zhu L, Luo Y, Liu Y, Sun S, Yuan J, Zhang L, Zhong W, Ma S, Yu Z, Zhou J, Chen X, Zhao J. Clostridium butyricum ameliorates indomethacin-induced enteropathy by promoting MUC2 secretion via suppressing the Notch pathway. Front Microbiol 2025; 16:1509876. [PMID: 40177488 PMCID: PMC11961966 DOI: 10.3389/fmicb.2025.1509876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a serious clinical complication with no effective treatments available. Modulating the intestinal microbiota through dietary and nutritional targets is a promising strategy for preventing NSAID enteropathy. This study aimed to investigate the protective effect and underlying mechanisms of the probiotic Clostridium butyricum (CB) on indomethacin (IND)-induced enteropathy. C57BL/6J mice received CB treatment for 14 days along with concurrent IND gavage for the final 7 days. Caco2 cells were stimulated with IND to evaluate the effect of CB supernatant (CBS) on the intestinal barrier function, and LS174T cells were used to validate the modulatory action of CBS on the Notch signaling pathway. Our findings revealed that CB treatment prevented anorexia and weight loss, reduced the severity of enteropathy, and decreased the inflammatory response of the small intestine. CB also increased the expression of tight junction proteins and reduced permeability in mice and Caco2 cells. Additionally, CB suppressed apoptosis and promoted proliferation in the small intestine. Further research found that CB increased the number of goblet cells and MUC2 secretion. Mechanistically, CB may promote MUC2 secretion by suppressing the Notch signaling pathway, consistent with the results of intervention in LS174T cells with CBS. In conclusion, CB might prevent NSAID enteropathy by increasing MUC2 secretion through the inhibition of the Notch pathway. Our study identified the potential efficacy of CB as a preventive strategy against NSAID enteropathy and showed promising prospects for CB as a food supplement.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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Dong J, Jin Z, Li C, Yang J, Jiang Y, Li Z, Chen C, Zhang B, Ye Z, Hu Y, Ma J, Li P, Li Y, Wang D, Ji Z. Machine Learning Models With Prognostic Implications for Predicting Gastrointestinal Bleeding After Coronary Artery Bypass Grafting and Guiding Personalized Medicine: Multicenter Cohort Study. J Med Internet Res 2025; 27:e68509. [PMID: 40053791 PMCID: PMC11926454 DOI: 10.2196/68509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 02/04/2025] [Accepted: 02/13/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Gastrointestinal bleeding is a serious adverse event of coronary artery bypass grafting and lacks tailored risk assessment tools for personalized prevention. OBJECTIVE This study aims to develop and validate predictive models to assess the risk of gastrointestinal bleeding after coronary artery bypass grafting (GIBCG) and to guide personalized prevention. METHODS Participants were recruited from 4 medical centers, including a prospective cohort and the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. From an initial cohort of 18,938 patients, 16,440 were included in the final analysis after applying the exclusion criteria. Thirty combinations of machine learning algorithms were compared, and the optimal model was selected based on integrated performance metrics, including the area under the receiver operating characteristic curve (AUROC) and the Brier score. This model was then developed into a web-based risk prediction calculator. The Shapley Additive Explanations method was used to provide both global and local explanations for the predictions. RESULTS The model was developed using data from 3 centers and a prospective cohort (n=13,399) and validated on the Drum Tower cohort (n=2745) and the MIMIC cohort (n=296). The optimal model, based on 15 easily accessible admission features, demonstrated an AUROC of 0.8482 (95% CI 0.8328-0.8618) in the derivation cohort. In external validation, the AUROC was 0.8513 (95% CI 0.8221-0.8782) for the Drum Tower cohort and 0.7811 (95% CI 0.7275-0.8343) for the MIMIC cohort. The analysis indicated that high-risk patients identified by the model had a significantly increased mortality risk (odds ratio 2.98, 95% CI 1.784-4.978; P<.001). For these high-risk populations, preoperative use of proton pump inhibitors was an independent protective factor against the occurrence of GIBCG. By contrast, dual antiplatelet therapy and oral anticoagulants were identified as independent risk factors. However, in low-risk populations, the use of proton pump inhibitors (χ21=0.13, P=.72), dual antiplatelet therapy (χ21=0.38, P=.54), and oral anticoagulants (χ21=0.15, P=.69) were not significantly associated with the occurrence of GIBCG. CONCLUSIONS Our machine learning model accurately identified patients at high risk of GIBCG, who had a poor prognosis. This approach can aid in early risk stratification and personalized prevention. TRIAL REGISTRATION Chinese Clinical Registry Center ChiCTR2400086050; http://www.chictr.org.cn/showproj.html?proj=226129.
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Affiliation(s)
- Jiale Dong
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Department of Acute Abdomen Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Zhechuan Jin
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Chengxiang Li
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jian Yang
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yi Jiang
- Department of Cardiovascular Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, China
| | - Zeqian Li
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Cheng Chen
- Department of Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Beijing, China
| | - Bo Zhang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Zhaofei Ye
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yang Hu
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jianguo Ma
- School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, China
| | - Ping Li
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yulin Li
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Dongjin Wang
- Department of Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Beijing, China
| | - Zhili Ji
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Department of Acute Abdomen Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Baba Y, Kawano S, Takaki A, Kono Y, Horii J, Takahashi S, Kawai D, Kobayashi S, Okada H. Relevance of oxidative stress for small intestinal injuries induced by nonsteroidal anti-inflammatory drugs: A multicenter prospective study. Medicine (Baltimore) 2024; 103:e40849. [PMID: 39686450 PMCID: PMC11651428 DOI: 10.1097/md.0000000000040849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
Several reports revealed that oxidative stress was involved in the mouse model of nonsteroidal anti-inflammatory drug (NSAIDs)-induced small intestinal mucosal injuries. Thus, we aimed to investigate in the prospective clinical study, that the relevance of oxidative stress balance in small intestinal mucosal injury in NSAIDs users. We prospectively included 60 patients who had been taking NSAIDs continuously for more than 3 months and exhibited obscure gastrointestinal bleeding (number UMIN 000011775). Small intestinal mucosal injuries were assessed by capsule endoscopy (CE), and reactive oxygen metabolites (d-ROMs) levels and oxidant capacity (OXY) adsorbent test were performed to investigate the relevance of oxidative stress balance. More than half of the patients (N = 32, 53%) had small intestinal mucosal injuries by CE, and 14 patients (24%) had ulcers. The incidence of ulcers was relatively higher in nonaspirin users. Serum OXY levels were significantly lower in the mucosal injury group (P = .02), and d-ROM levels were significantly higher in the ulcer group (P < .01). In aspirin users, d-ROM and OXY levels did not differ significantly with respect to mucosal injuries or ulcers. However, in nonaspirin users, OXY level was significantly lower in the mucosal injury group (P = .04), and d-ROM levels were significantly higher in the ulcer group (P = .02). Nonaspirin NSAIDs-induced intestinal mucosal injury is associated with antioxidant systems, resulting in increased oxidative stress.
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Affiliation(s)
- Yuki Baba
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshiyasu Kono
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Joichiro Horii
- Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center, Fukuyama, Japan
| | - Sakuma Takahashi
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Daisuke Kawai
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Sayo Kobayashi
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan
| | - Hiroyuki Okada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Kim JE, Lee YC, Kim TS, Kim ER, Hong SN, Kim YH, Kim K, Chang DK. Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors. Gut Liver 2024; 18:1026-1036. [PMID: 38468192 PMCID: PMC11565003 DOI: 10.5009/gnl230372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 12/11/2023] [Accepted: 12/20/2023] [Indexed: 03/13/2024] Open
Abstract
Background/Aims : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.
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Affiliation(s)
- Ji Eun Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yeong Chan Lee
- Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Tae Se Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Ran Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Dong Kyung Chang
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Lee HJ, Moon JW, Koh SJ, Im JP, Kim BG, Kim JS. Effect of tegoprazan, a novel potassium-competitive acid blocker, on non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. Sci Rep 2024; 14:27173. [PMID: 39511288 PMCID: PMC11543827 DOI: 10.1038/s41598-024-78581-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/01/2024] [Indexed: 11/15/2024] Open
Abstract
As the non-steroidal anti-inflammatory drugs (NSAIDs) are typically used in the treatment of chronic conditions, the incidence of NSAID-induced enteropathy is increasing. Given the challenges associated with discontinuing NSAIDs, effective preventive and treatment strategies are crucial. We assessed the effect of tegoprazan on NSAID-induced enteropathy. Human epithelial cells (HIEC-6, HT-29, and Caco-2) were treated with indomethacin and tegoprazan. Cell viability, expression levels of tight-junction proteins, levels of proinflammatory cytokines, and apoptosis were assessed by conducting MTT assays, RT-PCR, western blotting, and immunofluorescence staining, respectively. Tegoprazan significantly ameliorated the inhibition of cell proliferation induced by indomethacin. Tegoprazan also mitigated the suppression of occludin and ZO-1 expression by indomethacin, thereby restoring intestinal permeability. Additionally, tegoprazan reversed the indomethacin-induced elevation of the levels of proinflammatory cytokines and the rate of apoptosis of small intestinal epithelial cells. Our findings indicate that tegoprazan exerts a protective effect against NSAID-induced injury to small intestinal epithelial cells. The effect involves enhancement of the expression levels of tight junction proteins and the suppression of inflammation and apoptosis.
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Affiliation(s)
- Hyun Jung Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
| | - Ji Wook Moon
- BK21 Graduate Program, Department of Biomedical Sciences, Department of Anatomy, Korea University College of Medicine, Seoul, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
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Jones MP, Koloski NA, Walker MM, Holtmann GJ, Shah A, Eslick GD, Talley NJ. A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis. Am J Gastroenterol 2024; 119:1894-1900. [PMID: 38483301 DOI: 10.14309/ajg.0000000000002751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 03/06/2024] [Indexed: 04/24/2024]
Abstract
INTRODUCTION Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. METHODS General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. RESULTS Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). DISCUSSION Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.
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Affiliation(s)
- Michael P Jones
- School of Psychological Sciences, Macquarie University, North Ryde, New South Wales, Australia
| | - Natasha A Koloski
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia
| | - Marjorie M Walker
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
| | - Gerald J Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia
| | - Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia
| | - Guy D Eslick
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
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Garg K, Mohajeri MH. Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review. Brain Res Bull 2024; 207:110883. [PMID: 38244807 DOI: 10.1016/j.brainresbull.2024.110883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 01/12/2024] [Accepted: 01/16/2024] [Indexed: 01/22/2024]
Abstract
The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.
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Affiliation(s)
- Kirti Garg
- Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
| | - M Hasan Mohajeri
- Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland.
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Bordin DS, Livzan MA, Gaus OV, Mozgovoi SI, Lanas A. Drug-Associated Gastropathy: Diagnostic Criteria. Diagnostics (Basel) 2023; 13:2220. [PMID: 37443618 PMCID: PMC10341309 DOI: 10.3390/diagnostics13132220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/30/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. Here, we review the mechanisms of damage, risk factors and specific endoscopic, histopathological and clinical features of those drugs more often involved in gastric damage, namely NSAIDs, aspirin, anticoagulants, glucocorticosteroids, anticancer drugs, oral iron preparations and proton pump inhibitors. NSAID- and aspirin-associated forms of gastric damage are widely studied and have specific features, although they are often hidden by the coexistence of Helicobacter pylori infection. However, the damaging effect of anticoagulants and corticosteroids or oral iron therapy on the gastric mucosa is controversial. At the same time, the increased use of new antineoplastic drugs, such as checkpoint inhibitors, has opened up a new area of gastrointestinal damage that will be seen more frequently in the near future. We conclude that there is a need to expand and understand drug-induced gastrointestinal damage to prevent and recognize drug-associated gastropathy in a timely manner.
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Affiliation(s)
- Dmitry S. Bordin
- A.S. Loginov Moscow Clinical Scientific Center, Department of Pancreatic, Biliary and Upper Digestive Tract Disorders, 111123 Moscow, Russia
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
- Department of Outpatient Therapy and Family Medicine, Tver State Medical University, 170100 Tver, Russia
| | - Maria A. Livzan
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Olga V. Gaus
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Sergei I. Mozgovoi
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Angel Lanas
- Digestive Diseases Service, Aragón Health Research Institute (IIS Aragón), University Clinic Hospital, University of Zaragoza, 50009 Zaragoza, Spain
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Grinevich VB, Lazebnik LB, Kravchuk YA, Radchenko VG, Tkachenko EI, Pershko AM, Seliverstov PV, Salikova CP, Zhdanov KV, Kozlov KV, Makienko VV, Potapova IV, Ivanyuk ES, Egorov DV, Sas EI, Korzheva MD, Kozlova NM, Ratnikova AK, Ratnikov VA, Sitkin SI, Bolieva LZ, Turkina CV, Abdulganieva DI, Ermolova TV, Kozhevnikova SA, Tarasova LV, Myazin RG, Khomeriki NM, Pilat TL, Kuzmina LP, Khanferyan RA, Novikova VP, Polunina AV, Khavkin AI. Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:4-68. [DOI: 10.31146/1682-8658-ecg-208-12-4-68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Summary Post- COVID syndrome refers to the long-term consequences of a new coronavirus infection COVID-19, which includes a set of symptoms that develop or persist after COVID-19. Symptoms of gastrointestinal disorders in post- COVID syndrome, due to chronic infl ammation, the consequences of organ damage, prolonged hospitalization, social isolation, and other causes, can be persistent and require a multidisciplinary approach. The presented clinical practice guidelines consider the main preventive and therapeutic and diagnostic approaches to the management of patients with gastroenterological manifestations of postCOVID syndrome. The Guidelines were approved by the 17th National Congress of Internal Medicine and the 25th Congress of Gastroenterological Scientifi c Society of Russia.
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Affiliation(s)
| | - L. B. Lazebnik
- A. I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | | | | | | | - K. V. Kozlov
- Military Medical Academy named after S. M. Kirov
| | | | | | | | - D. V. Egorov
- Military Medical Academy named after S. M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S. M. Kirov
| | | | | | - A. K. Ratnikova
- North-West District Scientifi c and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency
| | - V. A. Ratnikov
- North-West District Scientifi c and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency
| | - S. I. Sitkin
- North-Western state medical University named after I. I. Mechnikov;
Almazov National Medical Research Centre
| | | | | | | | - T. V. Ermolova
- North-Western state medical University named after I. I. Mechnikov
| | | | | | | | - N. M. Khomeriki
- Moscow Regional Research Clinical Institute n. a. M. F. Vladimirsky”
| | - T. L. Pilat
- Scientifi c Research Institute of labour medicine named after academician N. F. Izmerov
| | - L. P. Kuzmina
- Scientifi c Research Institute of labour medicine named after academician N. F. Izmerov;
I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - A. I. Khavkin
- Russian National Research Medical University named after N. I. Pirogov
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11
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Ma Y, Wu Y, Wang X, Gao G, Zhou X. Research Progress of Near-Infrared Fluorescent Probes Based on 1,3-Dichloro-7-hydroxy-9,9-dimethyl-2(9 H)-acridone (DDAO). CHINESE J ORG CHEM 2023. [DOI: 10.6023/cjoc202206044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
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12
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Vandna, Ahlawat S, Sharma KK, Mohan H. Proteomic, biochemical, histopathological, and elevated plus maze analysis reveals the gut damaging role of ketoprofen with Yersinia enterocolitica and altered behavior in Wistar rats. Toxicol Appl Pharmacol 2022; 457:116315. [PMID: 36372189 DOI: 10.1016/j.taap.2022.116315] [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: 07/14/2022] [Revised: 10/20/2022] [Accepted: 11/06/2022] [Indexed: 11/13/2022]
Abstract
The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is known to damage the intestinal epithelial cells (IECs) that play numerous important roles, including nutrient absorption and barrier protection. In the current study, we determined the effect of ketoprofen on the rat gut when administered with Yersinia enterocolitica. On performing the label-free quantitation of the rat gut proteins, the expression of 494 proteins out of 1628 proteins was altered, which has a profound effect on NF-kB signaling pathway, immune system, dysbiosis, and gut injury. Further, the biochemical [enhanced malondialdehyde (MDA) & hepatic enzyme activities and reduced serotonin & antioxidants levels i.e., catalase (CAT) and superoxide dismutase (SOD)] and histopathological analysis suggested the significant damage in treated rats, compared to control rats. Lastly, the elevated plus maze (EPM) study confirmed high levels of anxiety in treated rats in comparison to the control group. Altogether, results suggest that the co-administration of ketoprofen with Y. enterocolitica damages gut, alters hepatic enzyme activities, and affects behavioral responses in the treated rats.
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Affiliation(s)
- Vandna
- Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak 124001, Haryana, India
| | - Shruti Ahlawat
- Department of Microbiology, Maharshi Dayanand University, Rohtak 124001, Haryana, India
| | - Krishna Kant Sharma
- Department of Microbiology, Maharshi Dayanand University, Rohtak 124001, Haryana, India.
| | - Hari Mohan
- Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak 124001, Haryana, India.
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13
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Effects of Canine-Obtained Lactic-Acid Bacteria on the Fecal Microbiota and Inflammatory Markers in Dogs Receiving Non-Steroidal Anti-Inflammatory Treatment. Animals (Basel) 2022; 12:ani12192519. [PMID: 36230259 PMCID: PMC9558503 DOI: 10.3390/ani12192519] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/16/2022] [Accepted: 09/18/2022] [Indexed: 11/17/2022] Open
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) may cause enteropathy in dogs and probiotics may be one option to prevent this. The objective of this study was to determine whether the administration of canine-obtained lactic acid bacteria (LAB) has an effect on the frequency of diarrhea, the composition of the fecal microbiota, and/or markers of gastrointestinal inflammation in dogs receiving NSAIDs when compared to dogs given NSAIDs and a placebo. A total of 22 dogs treated with NSAIDs for various clinical indications were enrolled in a seven-day randomized, double-blinded placebo-controlled interventional study. Dogs were randomized to receive either placebo or LAB, a product containing Limosilactobacillus fermentum, Lacticaseibacillus rhamnosus, and Lactiplantibacillus plantarum. Fecal samples were collected on days one and seven. The fecal microbiota was evaluated using the fecal dysbiosis index (DI) and individual bacterial taxa. Fecal calprotectin (CP) and S100A12/Calgranulin C concentrations were used as markers of gastrointestinal inflammation. There was a difference in frequency of diarrhea between groups, with it affecting 4/12 dogs (33%) in the placebo group and 1/10 dogs (10%) in the LAB group, but this difference did not reach statistical significance (p = 0.32). There was a correlation between S100A12 and CP (p < 0.001), and Clostridium perfringens correlated with S100A12 (p < 0.015). Neither treatment significantly affected S100A12 (p = 0.37), CP (p = 0.12), or fecal DI (p = 0.65). This study suggests that LAB is a safe supplement to use for short-term treatment in NSAID-treated dogs, but further studies are needed to determine its potential to prevent NSAID-induced enteropathy in dogs.
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14
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Lyu X, Chen J, Gao X, Yang J. Emerging story of gut dysbiosis in spondyloarthropathy: From gastrointestinal inflammation to spondyloarthritis. Front Cell Infect Microbiol 2022; 12:973563. [PMID: 36072223 PMCID: PMC9441705 DOI: 10.3389/fcimb.2022.973563] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
As a set of inflammatory disorders, spondyloarthritis (SpA) exhibits distinct pathophysiological, clinical, radiological, and genetic characteristics. Due to the extra-articular features of this disorder, early recognition is crucial to limiting disability and improving outcomes. Gut dysbiosis has been linked to SpA development as evidence grows. A pathogenic SpA process is likely to occur when a mucosal immune system interacts with abnormal local microbiota, with subsequent joint involvement. It is largely unknown, however, how microbiota alterations predate the onset of SpA within the “gut-joint axis”. New microbiome therapies, such as probiotics, are used as an adjuvant therapy in the treatment of SpA, suggesting that the modulation of intestinal microbiota and/or intestinal barrier function may contribute to the prevention of SpA. In this review, we highlight the mechanisms of SpA by which the gut microbiota impacts gut inflammation and triggers the activation of immune responses. Additionally, we analyze the regulatory role of therapeutic SpA medication in the gut microbiota and the potential application of probiotics as adjunctive therapy for SpA.
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Affiliation(s)
- Xing Lyu
- Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jieli Chen
- Discipline Construction Office, Tianjin Medical University, Tianjin, China
| | - Xingjie Gao
- Department of Biochemistry and Molecular Biology, Department of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Science, Tianjin Medical University, Tianjin, China
| | - Jie Yang
- Department of Biochemistry and Molecular Biology, Department of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Science, Tianjin Medical University, Tianjin, China
- *Correspondence: Jie Yang,
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15
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Trukhan DI. Disorders of intestinal microbiocenosis: expanding the application of probiotics. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2022:132-143. [DOI: 10.21518/2079-701x-2022-16-7-132-143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The problem of interaction between a person and the intestinal microbiome is surrounded by many secrets and mysteries. The bacterial flora of the gastrointestinal tract has a local and systemic effect not only on the digestive system, but also on the entire body as a whole. Numerous studies have proved the pathogenetic relationship of the state of the intestinal biocenosis not only with diseases of the gastrointestinal tract, but also with pathological processes from other organs and systems of the body. In terms of its role in maintaining homeostasis, the intestinal microflora is not inferior to any other vital organ. In the presented review, the current aspects of the terminology and clinic of disorders of intestinal microbiocenosis are considered. Probiotics occupy an important place in the complex therapy of intestinal microbiocenosis disorders and the corresponding clinical manifestations. The review considers the main mechanisms of probiotic / host interaction, non-immunological and immunological effects of probiotics and the requirements for them, the main directions of use of representatives of the normal microflora Bifidobacterium and Lactobacillus. The data of meta-analyzes and systematic reviews, testifying to the expansion of indications for the appointment of probiotics, are considered the possibilities of probiotics in the complex therapy of Helicobacter pylori infection, syndrome of increased epithelial intestinal permeability, and the prevention of respiratory infections.The review concludes with the results of a search in the PubMed database on the possibility of using probiotics in the prevention and treatment of a new coronavirus infection COVID-19. The availability of modern, effective and safe probiotics in the arsenal of a practical doctor (primarily a general practitioner and general practitioner), and their use, contributes to the optimization of drug therapy not only in gastroenterological patients, but also in patients with other somatic pathologies, including those with new coronavirus infection COVID-19.
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16
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Oncel S, Basson MD. Gut homeostasis, injury, and healing: New therapeutic targets. World J Gastroenterol 2022; 28:1725-1750. [PMID: 35633906 PMCID: PMC9099196 DOI: 10.3748/wjg.v28.i17.1725] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/12/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis, which depends upon the balance between mucosal injury by destructive factors and healing via protective factors. The persistence of noxious agents such as acid, pepsin, nonsteroidal anti-inflammatory drugs, or Helicobacter pylori breaks down the mucosal barrier and injury occurs. Depending upon the size and site of the wound, it is healed by complex and overlapping processes involving membrane resealing, cell spreading, purse-string contraction, restitution, differentiation, angiogenesis, and vasculogenesis, each modulated by extracellular regulators. Unfortunately, the gut does not always heal, leading to such pathology as peptic ulcers or inflammatory bowel disease. Currently available therapeutics such as proton pump inhibitors, histamine-2 receptor antagonists, sucralfate, 5-aminosalicylate, antibiotics, corticosteroids, and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract. More recent studies have focused on improving mucosal defense or directly promoting mucosal repair. Many investigations have sought to enhance mucosal defense by stimulating mucus secretion, mucosal blood flow, or tight junction function. Conversely, new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin, talin, Ehm2, filamin-a, gelsolin, and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase. This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
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Affiliation(s)
- Sema Oncel
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
| | - Marc D Basson
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
- Department of Surgery, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
- Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
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17
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Arima T, Morimoto K, Terai K, Kawamoto K, Muroya K, Koba Y, Omura T. Small bowel bleeding treated successfully with transcatheter arterial embolization with imipenem/cilastatin. Acute Med Surg 2022; 9:e733. [PMID: 35169486 PMCID: PMC8836219 DOI: 10.1002/ams2.733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 01/20/2022] [Accepted: 01/24/2022] [Indexed: 11/13/2022] Open
Abstract
Background Small bowel bleeding is an uncommon cause of lower gastrointestinal bleeding, which may require different management. Case Presentation A 37‐year‐old man presenting with hematochezia was promptly diagnosed with small bowel bleeding by computed tomography angiography. Transcatheter arterial embolization was carried out because the patient's hemodynamic status deteriorated. Hemostasis was achieved by embolization with imipenem/cilastatin, although superselective embolization failed. Capsule endoscopy revealed multiple ulcers and erosions. Drug‐induced small bowel injury was suspected to be the cause of small bowel bleeding. Conclusion Computed tomography angiography can facilitate the management of lower gastrointestinal bleeding. Considering transcatheter arterial embolization and choosing an optimal embolic agent depending on the situation are important in the management of hemodynamically unstable patients.
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Affiliation(s)
- Takahiro Arima
- Department of Surgery Higashiyamato Hospital Higashiyamato Japan
| | - Kohei Morimoto
- Department of Radiology National Disaster Medical Center Tachikawa Japan
| | - Kiyoshi Terai
- Department of Gastroenterology Higashiyamato Hospital Higashiyamato Japan
| | - Ken Kawamoto
- Department of Surgery Higashiyamato Hospital Higashiyamato Japan
| | - Ken Muroya
- Department of Surgery Higashiyamato Hospital Higashiyamato Japan
| | - Yuji Koba
- Department of Surgery Higashiyamato Hospital Higashiyamato Japan
| | - Takashi Omura
- Department of Surgery Higashiyamato Hospital Higashiyamato Japan
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18
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Głowacka U, Magierowska K, Wójcik D, Hankus J, Szetela M, Cieszkowski J, Korbut E, Danielak A, Surmiak M, Chmura A, Wallace JL, Magierowski M. Microbiome Profile and Molecular Pathways Alterations in Gastrointestinal Tract by Hydrogen Sulfide-Releasing Nonsteroidal Anti-Inflammatory Drug (ATB-352): Insight into Possible Safer Polypharmacy. Antioxid Redox Signal 2022; 36:189-210. [PMID: 33678013 DOI: 10.1089/ars.2020.8240] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Aims: Nonsteroidal anti-inflammatory drugs, including ketoprofen, induce adverse effects within the gastrointestinal (GI)-tract. Hydrogen sulfide (H2S) is an antioxidative gaseous mediator contributing to GI-protection. We aimed to evaluate the GI safety of a novel H2S-releasing derivative of ketoprofen (ATB-352) versus classic ketoprofen and the molecular mechanisms of their activity after chronic treatment in experimental animal models. Results: Ketoprofen (10 mg/kg/day) administered intragastrically for 7 days in contrast with ATB-352 (14 mg/kg/day) reduced mucosal H2S content inducing GI damage with significantly increased injury score, altered intestinal microbiome profile, and modulation of more than 50% of 36 investigated molecular sensors (e.g., mammalian target of rapamycin or suppressor of cytokine signaling 3 [SOCS3]). Polypharmacy with aspirin (10 mg/kg/day) enhanced ketoprofen toxicity not affecting GI safety of ATB-352. Omeprazole (20 mg/kg/day) decreased ketoprofen-induced injury to the level of ATB-352 alone. Both compounds combined or not with aspirin or omeprazole maintained the ability to inhibit cyclooxygenase (COX) activity manifested by decreased prostaglandin production. Innovation and Conclusions: Ketoprofen-induced H2S-production decrease and intestinal microbiome profile alterations lead to GI toxicity observed on macro-/microscopic and molecular levels. Ketoprofen but not ATB-352 requires concomitant treatment with omeprazole to eliminate GI adverse effects. ATB-352 applied alone or in a polypharmacy setting with aspirin effectively inhibited COX and maintained GI safety due to H2S-release. Neither compound affected DNA oxidation in the GI mucosa, but ATB-352 had lower impact on molecular oxidative/inflammatory response pathways and intestinal microbiome. The GI safety of ATB-352 could be due to the involvement of heme oxygenase 1 and SOCS3 pathway activation. Antioxid. Redox Signal. 36, 189-210.
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Affiliation(s)
- Urszula Głowacka
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | | | - Dagmara Wójcik
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | - Jerzy Hankus
- Department of Pathomorphology, Jagiellonian University Medical College, Cracow, Poland
| | - Małgorzata Szetela
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | - Jakub Cieszkowski
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | - Edyta Korbut
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | - Aleksandra Danielak
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | - Marcin Surmiak
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.,Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Anna Chmura
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
| | - John L Wallace
- Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada
| | - Marcin Magierowski
- Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
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19
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Azimirad M, Noori M, Raeisi H, Yadegar A, Shahrokh S, Asadzadeh Aghdaei H, Bentivegna E, Martelletti P, Petrosillo N, Zali MR. How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms? Front Med (Lausanne) 2021; 8:775063. [PMID: 34966759 PMCID: PMC8710593 DOI: 10.3389/fmed.2021.775063] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/22/2021] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) has rapidly spread all over the world with a very high rate of mortality. Different symptoms developed by COVID-19 infection and its impacts on various organs of the human body have highlighted the importance of both coinfections and superinfections with other pathogens. The gastrointestinal (GI) tract is vulnerable to infection with COVID-19 and can be exploited as an alternative transmission route and target for virus entry and pathogenesis. The GI manifestations of COVID-19 disease are associated with severe disease outcomes and death in all age groups, in particular, elderly patients. Empiric antibiotic treatments for microbial infections in hospitalized patients with COVID-19 in addition to experimental antiviral and immunomodulatory drugs may increase the risk of antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI). Alterations of gut microbiota are associated with depletion of beneficial commensals and enrichment of opportunistic pathogens such as C. difficile. Hence, the main purpose of this review is to explain the likely risk factors contributing to higher incidence of CDI in patients with COVID-19. In addition to lung involvement, common symptoms observed in COVID-19 and CDI such as diarrhea, highlight the significance of bacterial infections in COVID-19 patients. In particular, hospitalized elderly patients who are receiving antibiotics might be more prone to CDI. Indeed, widespread use of broad-spectrum antibiotics such as clindamycin, cephalosporins, penicillin, and fluoroquinolones can affect the composition and function of the gut microbiota of patients with COVID-19, leading to reduced colonization resistance capacity against opportunistic pathogens such as C. difficile, and subsequently develop CDI. Moreover, patients with CDI possibly may have facilitated the persistence of SARS-CoV-2 viral particles in their feces for approximately one month, even though the nasopharyngeal test turned negative. This coinfection may increase the potential transmissibility of both SARS-CoV-2 and C. difficile by fecal materials. Also, CDI can complicate the outcome of COVID-19 patients, especially in the presence of comorbidities or for those patients with prior exposure to the healthcare setting. Finally, physicians should remain vigilant for possible SARS-CoV-2 and CDI coinfection during the ongoing COVID-19 pandemic and the excessive use of antimicrobials and biocides.
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Affiliation(s)
- Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Noori
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamideh Raeisi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Enrico Bentivegna
- Internal Medicine and Emergency Medicine, St'Andrea Hospital, Sapienza University, Rome, Italy
| | - Paolo Martelletti
- Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy
| | - Nicola Petrosillo
- Infectious Diseases Service, University Hospital Campus Bio-Medico, Rome, Italy
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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20
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Cho M, Bu Y, Park JW, Rahman H, Ko SJ. Efficacy of complementary medicine for nonsteroidal anti-inflammatory drug-induced small intestinal injuries: A narrative review. Medicine (Baltimore) 2021; 100:e28005. [PMID: 35049210 PMCID: PMC9191556 DOI: 10.1097/md.0000000000028005] [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: 07/15/2021] [Accepted: 11/11/2021] [Indexed: 11/26/2022] Open
Abstract
Nonsteroidal anti-inflammatory drug-induced small bowel injuries (NSIs) have been largely ignored for decades due to the focus on nonsteroidal anti-inflammatory drug gastropathy. With the visualization of the small intestines enabled by video capsule endoscopy, the frequency and severity of NSIs have become more evident. NSIs have a complex pathophysiology, and no effective preventive or treatment options have been proven. Complementary and alternative medicine (CAM) has been used to treat disorders of the small intestine, and more research on its effectiveness for NSIs has been conducted.We reviewed the current evidence and mechanisms of action of CAMs on NSI. Clinical and experimental studies on the effect of CAMs on NSIs were performed using 10 databases.Twenty-two studies (3 clinical and 19 in vivo experimental studies) were included in the final analysis involving 10 kinds of CAMs: bovine colostrum, Orengedokuto (coptis), muscovite, licorice, grape seed, wheat, brown seaweed, Ganoderma lucidum fungus mycelia, Chaenomeles speciosa (sweet) Nakai (muguasantie), and Jinghua Weikang capsule. The mechanisms of CAM include an increase in prostaglandin E2, reparation of the enteric nervous system, inhibition of pro-inflammatory cytokines, reduction of intestinal permeability and enteric bacterial numbers, decrease in oxidative stress, and modulation of small intestinal motility.CAM may be a novel alternative option for treating and preventing NSI, and further studies on human and animal models with relevant comorbidities are warranted.
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Affiliation(s)
- Minji Cho
- Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Youngmin Bu
- Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Jae-Woo Park
- Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Hasanur Rahman
- Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
| | - Seok-Jae Ko
- Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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21
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Otani K, Watanabe T, Higashimori A, Nadatani Y, Nagami Y, Taira K, Inui K, Fujiwara Y. Effects of Colchicine on NSAID-Induced Severe Small Intestinal Damage: A Pilot Study. Digestion 2021; 102:803-808. [PMID: 33202409 DOI: 10.1159/000511255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 08/31/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND We previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) induced small intestinal damage through nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-dependent interleukin-1β secretion in mice. Our further study demonstrated that colchicine, a therapeutic agent for gout, significantly suppressed NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation in mice. However, clinical efficacy of colchicine for NSAID-induced small intestinal damage has not been established. OBJECTIVES We examined the clinical efficacy of colchicine in patients with NSAID-induced severe small intestinal damage as an animal-to-human translational research. METHODS This is a single-center, single-arm, prospective pilot study. From February 2017 to March 2019, we performed video capsule endoscopy (VCE) to screen 10 patients who took NSAIDs continuously for more than 3 months, and 7 of those with severe small intestinal damage were enrolled. Participants were treated with oral colchicine 0.5 mg twice daily for 8 weeks and thereafter followed up with blood tests and VCE. RESULTS After 8 weeks of colchicine treatment, complete healing was achieved in 4 patients (57.1%), and the median number of small erosions decreased significantly from 7.0 (range, 5.0-10.5) to 0.0 (range, 0.0-2.3) (p = 0.031). One patient withdrew due to diarrhea, and 5 patients revealed slightly elevated liver enzymes during the study. No other adverse events including changes in blood tests and clinical symptoms were observed. CONCLUSIONS Colchicine treatment achieved a high rate of complete healing in patients with NSAID-induced severe small intestinal damage.
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Affiliation(s)
- Koji Otani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan,
| | - Akira Higashimori
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yuji Nadatani
- Department of Premier Preventive Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koichi Taira
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kentaro Inui
- Department of Orthopaedic Surgery, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Zhang WT, Wang MR, Hua GD, Li QY, Wang XJ, Lang R, Weng WL, Xue CM, Zhu BC. Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis. Front Pharmacol 2021; 12:730681. [PMID: 34475825 PMCID: PMC8406693 DOI: 10.3389/fphar.2021.730681] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 07/12/2021] [Indexed: 11/23/2022] Open
Abstract
Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future.
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Affiliation(s)
- Wan-Tong Zhang
- Institute of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Miao-Ran Wang
- Department of Endocrinology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guo-Dong Hua
- Department of Pharmacy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Qiu-Yan Li
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Xu-Jie Wang
- Institute of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Rui Lang
- Department of Nephrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wei-Liang Weng
- Institute of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Chun-Miao Xue
- Department of Pharmacy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Bao-Chen Zhu
- Department of Pharmacy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Xu M, Liu F, Zhou W, He B, Tan S. Preparation and preliminary quality evaluation of aspirin/L-glutamate compound pellets. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:116. [PMID: 34460000 PMCID: PMC8405465 DOI: 10.1007/s10856-021-06594-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 08/16/2021] [Indexed: 06/13/2023]
Abstract
L-glutamate is an important component of protein. It can prevent gastrointestinal damage caused by NSAIDs. We constructed two-phase enteric-coated granules of aspirin and L-glutamate compound by extrusion spheronization method and fluidized bed coating. The subliminal effective dose of L-glutamate is 100 mg/kg tested by model of gastric ulcer of rats induced by aspirin and drug administration. HPLC-UV and UV-Vis methods were adopted to determine content and cumulative release of aspirin and L-glutamate as quality analysis method indexes. The prescription and process optimization were carried out with yield, sphericity and dissolution. The two-phase compound granules have good sphericity of 0.93 ± 0.05 (aspirin pellets) and 0.94 ± 0.02 (L-glutamate pellets), content of salicylic acid (0.24 ± 0.03)%, dissolution of aspirin (2.36 ± 0.11)%. Quality evaluation and preliminary stability meet the commercial requirements. The stored environment of compound preparation should be sealed in a cool and dark place.
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Affiliation(s)
- Mengchang Xu
- Academician Workstation, Changsha Medical University, Changsha, 410219, China
| | - Fenglin Liu
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China
| | - Wenhu Zhou
- Academician Workstation, Changsha Medical University, Changsha, 410219, China.
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China.
| | - Binsheng He
- Academician Workstation, Changsha Medical University, Changsha, 410219, China
| | - Songwen Tan
- Academician Workstation, Changsha Medical University, Changsha, 410219, China.
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China.
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24
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Cañamares-Orbís P, Lanas Arbeloa Á. New Trends and Advances in Non-Variceal Gastrointestinal Bleeding-Series II. J Clin Med 2021; 10:3045. [PMID: 34300211 PMCID: PMC8303152 DOI: 10.3390/jcm10143045] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/03/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
The gastrointestinal tract is a long tubular structure wherein any point in the mucosa along its entire length could be the source of a hemorrhage. Upper (esophagel and gastroduodenal) and lower (jejunum, ileum, and colon) gastrointestinal bleeding are common. Gastroduodenal and colonic bleeding are more frequent than bleeding from the small bowel, but nowadays the entire gastrointestinal tract can be explored endoscopically and bleeding lesions can be locally treated successfully to stop or prevent further bleeding. The extensive use of antiplatelet and anticoagulants drugs in cardiovascular patients is, at least in part, the cause of the increasing number of patients suffering from gastrointestinal bleeding. Patients with these conditions are usually older and more fragile because of their comorbidities. The correct management of antithrombotic drugs in cases of gastrointestinal bleeding is essential for a successful outcome for patients. The influence of the microbiome in the pathogenesis of small bowel bleeding is an example of the new data that are emerging as potential therapeutic target for bleeding prevention. This text summarizes the latest research and advances in all forms of acute gastrointestinal bleeding (i.e., upper, small bowel and lower). Diagnosis is approached, and medical, endoscopic or antithrombotic management are discussed in the text in an accessible and comprehensible way.
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Affiliation(s)
- Pablo Cañamares-Orbís
- Gastroenterology, Hepatology and Nutrition Unit, San Jorge University Hospital, 22004 Huesca, Spain
| | - Ángel Lanas Arbeloa
- IIS Aragón, CIBERehd, 50009 Zaragoza, Spain;
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, 50009 Zaragoza, Spain
- University of Zaragoza, 500009 Zaragoza, Spain
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25
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Effect of Weikang Capsule () on Aspirin-Related Gastric and Small Intestinal Mucosal Injury. Chin J Integr Med 2021; 27:621-625. [PMID: 34105097 DOI: 10.1007/s11655-021-3300-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the effects of Weikang Capsule (, WKC) on aspirin-related gastric and small intestinal mucosal injury by magnetically controlled capsule endoscopy (MCCE). METHODS Patients taking enteric-coated aspirin aged 40-75 years were enrolled in Beijing Anzhen Hospital, Capital Medical University from January 2019 to December 2019. The patients continued taking aspirin Tablet (100 mg per day) and underwent MCCE before and after 1-month combined treatment with WKC (0.9 g per time orally, 3 times per day). The gastrointestinal symptom score, gastric Lanza score, the duodenal, jejunal and ileal mucosal injury scores were used to evaluate the gastrointestinal injury before and after treatment. Adverse events including nausea, vomiting, abdominal pain, abdominal distension, abdominal discomfort, dizziness, or headache during MCCE and combined treatment were observed and recorded. RESULTS Twenty-two patients (male/female, 13/9) taking enteric-coated aspirin aged 59.5 ± 11.3 years with a duration of aspirin use of 28.0 (1.0, 48.0) months were recruited. Compared with pre-treatment, the gastrointestinal symptom rating scale scores, gastric Lanza scores, and duodenal mucosal injury scores were significantly reduced after 1-month WKC treatment (P<0.05), and jejunal and ileal mucosal injury scores showed no obvious change. No adverse events occurred during the trial. CONCLUSIONS WKC can alleviate gastrointestinal symptoms, as well as gastric and duodenal mucosal injuries, in patients taking enteric-coated aspirin; it does not aggravate jejunal or ileal mucosal injury, which may be an effective alternative for these patients (Clinical trial registry No. ChiCTR1900025451).
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Grinevich VB, Kravchuk YA, Ped VI, Sas EI, Salikova SP, Gubonina IV, Tkachenko EI, Sitkin SI, Lazebnik LB, Golovanova EV, Belousova EA, Makarchuk PA, Eremina EY, Sarsenbaeva AS, Abdulganieva DI, Tarasova LV, Gromova OA, Ratnikov VA, Kozlov KV, Ratnikova AK. Management of patients with digestive diseases during the COVID-19 pandemic. Clinical Practice Guidelines by the Russian scientific medical society of internal medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (2nd edition). EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:5-82. [DOI: 10.31146/1682-8658-ecg-187-3-5-82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
The presented clinical practice guidelines of the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The guidelines were approved by the XXIII Congress of the GSSR and the 22nd International Slavonic-Baltic Scientifi c Forum “St. Petersburg - Gastro-2020 ON-LINE” (St. Petersburg, June 11, 2020). The presented clinical practice guidelines of the Russian Scientific Medical Society of Internal Medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The recommendations were approved at the XV National Congress of Internal Medicine, XXIII Congress of NOGR on the basis of the 1st edition, adopted at the 22nd International Slavic- Baltic Scientific Forum “St. Petersburg - Gastro-2020 ON-LINE”.
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Affiliation(s)
| | | | - V. I. Ped
- Military Medical Academy named after S. M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S. M. Kirov
| | | | | | | | - S. I. Sitkin
- State Research Institute of Highly Pure Biopreparations of FMBA of Russia; Almazov National Medical Research Centre; North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - L. B. Lazebnik
- Moscow state University of Medicine a. Densitry named after A. I. Yevdokimov of the Ministry of Health of Russia
| | - E. V. Golovanova
- Moscow state University of Medicine a. Densitry named after A. I. Yevdokimov of the Ministry of Health of Russia
| | - E. A. Belousova
- State Budgetary Institution of Moscow Region “Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky”
| | - P. A. Makarchuk
- State Budgetary Institution of Moscow Region “Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky”
| | - E. Yu. Eremina
- Federal State Budgetary Educational Institution of Higher Education “National Research Ogarev Mordovia State University”
| | - A. S. Sarsenbaeva
- FSBEI HE SUSMU MOH Russia, st. Vorovskogo, 64, Ural Federal District
| | | | - L. V. Tarasova
- FSBEI of HE “The Chuvash State University n.a. I. N. Ulyanov”; BI of HE “The Surgut State University”
| | - O. A. Gromova
- Federal Research Center “Informatics and Management” of the Russian Academy of Sciences; Federal State Educational Institution of Higher Education Lomonosov Moscow State University
| | - V. A. Ratnikov
- Federal state budgetary institution “North-West District Scientific and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency“
| | - K. V. Kozlov
- Military Medical Academy named after S. M. Kirov
| | - A. K. Ratnikova
- Military Medical Academy named after S. M. Kirov; Federal state budgetary institution “North-West District Scientific and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency“
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27
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Mäkelä SM, Forssten SD, Kailajärvi M, Langén VL, Scheinin M, Tiihonen K, Ouwehand AC. Effects of Bifidobacterium animalis ssp. lactis 420 on gastrointestinal inflammation induced by a nonsteroidal anti-inflammatory drug: A randomized, placebo-controlled, double-blind clinical trial. Br J Clin Pharmacol 2021; 87:4625-4635. [PMID: 33908058 PMCID: PMC9291844 DOI: 10.1111/bcp.14880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 03/26/2021] [Accepted: 04/18/2021] [Indexed: 12/16/2022] Open
Abstract
Aims Use of nonsteroidal anti‐inflammatory drugs (NSAIDs) can cause damage to the gastric and duodenal mucosa. Some probiotics have proven useful in ameliorating the harmful side‐effects of NSAIDs. Our aim was to evaluate whether oral administration of Bifidobacterium animalis ssp. lactis 420 (B420) can attenuate the increase of calprotectin excretion into faeces induced by intake of diclofenac sustained‐release tablets. Methods A double‐blind, parallel‐group, placebo‐controlled and randomized clinical study was performed in 50 healthy male and female volunteers aged 20–40 years, in Finland. Study participation consisted of 4 phases: run‐in, intervention with B420 or placebo, B420 or placebo + NSAID treatment, and follow‐up. The primary outcome was the concentration of calprotectin in faeces. Secondary outcomes were haemoglobin and microbial DNA in faeces and blood haemoglobin levels. Results Intake of diclofenac increased the faecal excretion of calprotectin in both groups. The observed increases were 48.19 ± 61.55 μg/g faeces (mean ± standard deviation) in the B420 group and 31.30 ± 39.56 μg/g in the placebo group (difference estimate 16.90; 95% confidence interval: −14.00, 47.77; P = .276). There were no significant differences between the treatment groups in changes of faecal or blood haemoglobin. Faecal B. lactis DNA was much more abundant in the B420 group compared to the placebo group (ANOVA estimate for treatment difference 0.85 × 109/g faeces; 95% confidence interval: 0.50 × 109, 1.21 × 109; P < .0001). Conclusions Short‐term administration of the probiotic B420 did not protect the healthy adult study participants from diclofenac‐induced gastrointestinal inflammation as determined by analysis of faecal calprotectin levels.
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Affiliation(s)
- Sanna M Mäkelä
- Danisco Sweeteners Oy, IFF Health & Biosciences, ,Sokeritehtaantie 20, Kantvik, FI-02460, Finland
| | - Sofia D Forssten
- Danisco Sweeteners Oy, IFF Health & Biosciences, ,Sokeritehtaantie 20, Kantvik, FI-02460, Finland
| | - Marita Kailajärvi
- Clinical Research Services Turku (CRST) Oy and Institute of Biomedicine, University of Turku, Turku, Finland
| | - Ville L Langén
- Clinical Research Services Turku (CRST) Oy and Institute of Biomedicine, University of Turku, Turku, Finland.,Division of Medicine, Turku University Hospital, Turku, Finland
| | - Mika Scheinin
- Clinical Research Services Turku (CRST) Oy and Institute of Biomedicine, University of Turku, Turku, Finland.,Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland
| | - Kirsti Tiihonen
- Danisco Sweeteners Oy, IFF Health & Biosciences, ,Sokeritehtaantie 20, Kantvik, FI-02460, Finland
| | - Arthur C Ouwehand
- Danisco Sweeteners Oy, IFF Health & Biosciences, ,Sokeritehtaantie 20, Kantvik, FI-02460, Finland
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Chi T, Zhao Q, Wang P. Fecal 16S rRNA Gene Sequencing Analysis of Changes in the Gut Microbiota of Rats with Low-Dose Aspirin-Related Intestinal Injury. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8848686. [PMID: 33954200 PMCID: PMC8060078 DOI: 10.1155/2021/8848686] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 02/06/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The incidence of small intestinal injury caused by low-dose aspirin (LDA) is high, but the pathogenesis and intervention measures of it have not been elucidated. Recent studies have found gut microbiota to be closely associated with onset and development of NSAID-induced intestinal injury. However, studies of the changes in the gut microbiota of rats with LDA-related intestinal injury have been lacking recently. In this study, we investigated fecal 16S rRNA gene sequencing analysis of changes in the gut microbiota of rats with LDA-related intestinal injury. METHODS Sprague-Dawley (SD) rat models of small intestinal injury were established by intragastric administration of LDA. The small intestinal tissues and the fecal samples were harvested. The fecal samples were then analyzed using high-throughput sequencing of 16S rRNA V3-V4 amplicons. The gut microbiota composition and diversity were analyzed and compared using principal coordinate analysis (PCoA), nonmetric multidimensional scaling (NMDS) analysis, the unweighted pair-group method with arithmetic mean (UPGMA) clustering analysis, multivariate statistical analysis (ANOSIM, MetaStats, and LEfSe), and spatial statistics. RESULTS The LDA rat model was successfully established. Decreased Firmicutes and increased Bacteroidetes abundances in rats with LDA-induced small intestinal injury were revealed. MetaStats analysis between the before administration of LDA (CG) and after administration of LDA (APC) groups showed that the intestinal floras exhibiting significant differences (P < 0.05, q < 0.1) were Firmicutes, Bacteroides, Cyanobacteria, Melainabacteria, Coriobacteriia, Bacteroidia, Bacteroidales, Eubacteriaceae, and Streptococcaceae. In addition, the bacterial taxa showing significant differences between the control (NS) and APC groups were Firmicutes, Bacteroides, Verrucomicrobiaceae and Peptococcaceae. CONCLUSIONS The alterations in the gut microbiota composition and diversity of rats with LDA-related intestinal injury were found in the present study. The change of gut microbiota in LDA-related intestinal injury will lay the foundation for further research on the function and signaling pathways of the intestinal flora and promote the use of intestinal flora as drug targets to treat LDA-induced small intestinal injury.
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Affiliation(s)
- Tianyu Chi
- Departments of Gastroenterology, Xuanwu Hospital Capital Medical University, Beijing, China
| | - Quchuan Zhao
- Departments of Gastroenterology, Xuanwu Hospital Capital Medical University, Beijing, China
| | - Peili Wang
- Cardiovascular Center, Xi Yuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
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Effects of Bovine Colostrum with or without Egg on In Vitro Bacterial-Induced Intestinal Damage with Relevance for SIBO and Infectious Diarrhea. Nutrients 2021; 13:nu13031024. [PMID: 33809940 PMCID: PMC8004259 DOI: 10.3390/nu13031024] [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: 02/24/2021] [Revised: 03/12/2021] [Accepted: 03/18/2021] [Indexed: 02/08/2023] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) occurs commonly, is difficult to treat, and frequently recurs. Bovine colostrum (BC) and chicken eggs contain immunoglobulins and other components that possess antimicrobial, immunoregulatory, and growth factor activities; however, it is not known if they have the ability to reduce injury caused by the presence of bacteria associated with SIBO (Streptococcus, Escherichia coli, Staphylococcus, Bacteroides, Klebsiella, Enterococcus, and Proteus) and infectious diarrhea (enteropathogenic Escherichia coli, Salmonella). We examined the effects of BC, egg, or the combination, on bacterial growth and bacteria-induced changes in transepithelial electrical resistance (TEER) and bacterial translocation across confluent Caco-2 monolayers. BC, egg, or the combination did not affect bacterial growth. Adding bacteria to monolayers reduced TEER and (with minor variations among species) increased bacterial translocation, increased monolayer apoptosis (increased caspase-3 and Baxα, reduced Bcl2), increased intercellular adhesion molecule 1 (ICAM-1), and reduced cell adhesion molecules zonulin1 (ZO1) and claudin-1. BC, egg, or the combination reduced these effects (all p < 0.01) and caused additional increases in vascular endothelial growth factor (VEGF) and Heat Shock Protein 70 (Hsp70) expression. We conclude that BC ± egg strengthens mucosal integrity against a battery of bacteria relevant for SIBO and for infectious diarrhea. Oral BC ± egg may have clinical value for these conditions, especially SIBO where eradication of precipitating organisms may be difficult to achieve.
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Chao G, Hong X, Zhang S. Effects of Mast Cells Induced by NSAIDs Impair Intestinal Epithelial Barrier Function In Vivo and In Vitro. Inflammation 2021; 44:1396-1404. [PMID: 33566258 DOI: 10.1007/s10753-021-01424-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/04/2021] [Accepted: 01/19/2021] [Indexed: 02/07/2023]
Abstract
To explore the correlation between altered expression of mast cells and PAR-2 and impaired mucosal barrier in NSAIDs enteropathy through animal and cell experiments, and to elucidate the role of mast cells and PAR-2 in the pathogenesis of NSAIDs enteropathy and the regulatory mechanism of the tight junction of intestinal epithelium. Animal experiments: the NSAIDs-related small intestine injury model was established by intragastric administration of diclofenac sodium, and mast cells were detected by toluidine blue staining. Cell experiments: Intestinal epithelial cell line (IEC-6) was applied with diclofenac sodium and its activity was detected by CCK-8.IEC-6 and RBL-2H3 were co-cultured to evaluate the permeability of intestinal epithelial cells by detecting the concentration of potassium ion and LDH. The expressions of tight junction proteins (zo-1, claudin-1, occludin), cytoskeletal components (actin, tubulin, keratin) and par-2 were analyzed by Western Blot. In animal experiments, the number of mast cells was significantly increased after 24 h of action of diclofenac sodium. In cell experiments, the survival rate of IEC-6 cells decreased significantly when the concentration of diclofenac sodium is more than 50 μg/mL; after 24 h of co-culture, the potassium and LDH concentration in the co-culture group were significantly higher, and the expression of ZO-1, claudin-1, occludin, tubulin, and keratin was decreased. Mast cells activate PAR-2 in intestinal epithelial cells, downregulate the related proteins of cell tight junctions and cytoskeletal proteins, and increase the permeability of intestinal epithelial cells.
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Affiliation(s)
- Guanqun Chao
- Department of General Practice, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Xiaojie Hong
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shuo Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
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31
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Guo CG, Leung WK. Potential Strategies in the Prevention of Nonsteroidal Anti-inflammatory Drugs-Associated Adverse Effects in the Lower Gastrointestinal Tract. Gut Liver 2021; 14:179-189. [PMID: 31547642 PMCID: PMC7096237 DOI: 10.5009/gnl19201] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 07/09/2019] [Indexed: 12/21/2022] Open
Abstract
With the increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs), the incidence of lower gastrointestinal (GI) complications is expected to increase. However, unlike upper GI complications, the burden, pathogenesis, prevention and treatment of NSAID-associated lower GI complications remain unclear. To date, no cost-effective and safe protective agent has been developed that can completely prevent or treat NSAID-related lower GI injuries. Selective COX-2 inhibitors, misoprostol, intestinal microbiota modulation, and some mucoprotective agents have been reported to show protective effects on NSAID-induced lower GI injuries. This review aims to provide an overview of the current evidence on the prevention of NSAID-related lower GI injuries.
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Affiliation(s)
- Chuan-Guo Guo
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong
| | - Wai K Leung
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong
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Monteros MJM, Galdeano CM, Balcells MF, Weill R, De Paula JA, Perdigón G, Cazorla SI. Probiotic lactobacilli as a promising strategy to ameliorate disorders associated with intestinal inflammation induced by a non-steroidal anti-inflammatory drug. Sci Rep 2021; 11:571. [PMID: 33436961 PMCID: PMC7803994 DOI: 10.1038/s41598-020-80482-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 12/09/2020] [Indexed: 02/07/2023] Open
Abstract
Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. Hence, we investigated whether probiotics can control the onset of this severe condition in a murine model of intestinal inflammation induced by the NSAID, indomethacin. Probiotic supplementation to mice reduce the body weight loss, anemia, shortening of the small intestine, cell infiltration into the intestinal tissue and the loss of Paneth and Goblet cells associated with intestinal inflammation. Furthermore, a high antimicrobial activity in the intestinal fluids of mice fed with probiotics compared to animals on a conventional diet was elicited against several pathogens. Interestingly, probiotics dampened the oxidative stress and several local and systemic markers of an inflammatory process, as well as increased the secretion of IL-10 by regulatory T cells. Even more importantly, probiotics induced important changes in the large intestine microbiota characterized by an increase in anaerobes and lactobacilli, and a significant decrease in total enterobacteria. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis.
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Affiliation(s)
- María José Martínez Monteros
- Laboratorio de Inmunología, Centro de Referencia Para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Chacabuco 145 - (T4000ILC), Tucumán, Argentina
| | - Carolina Maldonado Galdeano
- Laboratorio de Inmunología, Centro de Referencia Para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Chacabuco 145 - (T4000ILC), Tucumán, Argentina
- Cátedra de Inmunología, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - María Florencia Balcells
- Laboratorio de Inmunología, Centro de Referencia Para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Chacabuco 145 - (T4000ILC), Tucumán, Argentina
| | | | | | - Gabriela Perdigón
- Laboratorio de Inmunología, Centro de Referencia Para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Chacabuco 145 - (T4000ILC), Tucumán, Argentina
| | - Silvia Inés Cazorla
- Laboratorio de Inmunología, Centro de Referencia Para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Chacabuco 145 - (T4000ILC), Tucumán, Argentina.
- Cátedra de Inmunología, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina.
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Wang X, Tang Q, Hou H, Zhang W, Li M, Chen D, Gu Y, Wang B, Hou J, Liu Y, Cao H. Gut Microbiota in NSAID Enteropathy: New Insights From Inside. Front Cell Infect Microbiol 2021; 11:679396. [PMID: 34295835 PMCID: PMC8290187 DOI: 10.3389/fcimb.2021.679396] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/10/2021] [Indexed: 12/15/2022] Open
Abstract
As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.
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Affiliation(s)
- Xianglu Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Qiang Tang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Huiqin Hou
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Wanru Zhang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Mengfan Li
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Danfeng Chen
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yu Gu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Jingli Hou
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China
- *Correspondence: Hailong Cao, ; Jingli Hou, ; Yangping Liu,
| | - Yangping Liu
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China
- *Correspondence: Hailong Cao, ; Jingli Hou, ; Yangping Liu,
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
- *Correspondence: Hailong Cao, ; Jingli Hou, ; Yangping Liu,
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Proton-pump inhibitors are associated with a high false-positivity rate in faecal immunochemical testing. J Gastroenterol 2021; 56:42-53. [PMID: 33159805 DOI: 10.1007/s00535-020-01738-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 10/11/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND False-positivity rates in faecal immunochemical test (FIT) can be affected by drug exposure. We aimed to assess the association between proton pump inhibitors (PPI) consumption and false positive (FP) results in a colorectal cancer (CRC) screening programme using electronic prescription records. METHODS A retrospective cohort study within a population-based screening program for CRC from 2010 to 2016 was performed. Participants with a conclusive FIT result and with prescription electronic data were included. An FP result was defined as having a positive FIT (≥ 20 µg haemoglobin/g faeces) and a follow-up colonoscopy without intermediate or high-risk lesions or CRC. Screening data were anonymously linked to the public data analysis program for health research and innovation (PADRIS) database that recorded patient diseases history and reimbursed medication. PPI exposure was defined as having retrieved at least one dispensation of PPI three months prior to the FIT. RESULTS A total of 89,199 tests (of 46,783 participants) were analysed, 4824 (5.4%) tested positive and the proportion of FP was 53.5%. Overall, 17,544 participants (19.7%) were PPI users prior to FIT performance. PPI exposure increased the probability of obtaining an FP FIT result from 50.4 to 63.3% (adjusted OR 1.39; 95% CI 1.18-1.65). Nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, antibiotics, and laxatives were also associated with an FP result. The effect of PPI was independent and showed a synergistic interaction with nonsteroidal anti-inflammatory drugs. CONCLUSION PPIs increase FIT positivity at the expense of FP results. The recommendation to avoid their use before FIT performance could reduce up to 3% of colonoscopies and 9% of FP results.
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Chao G, Dai J, Zhang S. Protective effect of naringin on small intestine injury in NSAIDs related enteropathy by regulating ghrelin/GHS-R signaling pathway. Life Sci 2020; 266:118909. [PMID: 33333047 DOI: 10.1016/j.lfs.2020.118909] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 11/16/2020] [Accepted: 12/08/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To investigate the mechanism of Ghrelin/GHS-R signaling pathway in small intestine injury induced by NSAIDs related enteropathy. To clarify the mechanism network of intestinal mucosal repair with naringin as a new therapeutic method. METHODS Naringin was used as the intervention method, observed the damage of small intestinal mucosa and detected the expression of ghrelin, GHS-R, leptin and TNF-α by electron microscopy, HE staining and immunohistochemistry. RESULTS Compared with the control group, the weight of rats in the model group decreased, the thickness of intestinal mucosa became thinner, the structure of intestinal mucosa changed, the expression of ghrelin, GHS-R and leptin decreased, the expression of TNF-α increased. Compared with the model group, the intestinal mucosa of the treatment group was repaired, the expression of ghrelin, GHS-R and leptin was increased, and the expression TNF-α was decreased. CONCLUSION The mechanism of intestinal mucosal damage in patients with NSAIDs related enteropathy may be related to the decreased expression of ghrelin, GHS-R and leptin, and promotion of TNF-α secretion. Naringin can effectively promote the secretion of ghrelin and leptin, the expression of GSH-R, and inhibit the release of TNF-α, so as to repair intestinal mucosa naringin will become a new method to treat and prevent NSAIDs related intestinal diseases.
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Affiliation(s)
- Guanqun Chao
- Department of General Practice, Sir Run Run Shaw Hospital, Zhejiang University, China.
| | - Jian Dai
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China
| | - Shuo Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China.
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Sánchez-Trigueros MI, Méndez-Cruz F, Pineda-Peña EA, Rivera-Espinoza Y, Castañeda-Hernández G, Chávez-Piña AE. Synergistic protective effects between docosahexaenoic acid and omeprazole on the gastrointestinal tract in the indomethacin-induced injury model. Drug Dev Res 2020; 82:543-552. [PMID: 33319390 DOI: 10.1002/ddr.21772] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/04/2020] [Accepted: 12/04/2020] [Indexed: 02/06/2023]
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs due to their antipyretic, anti-inflammatory, and analgesic properties. However, NSAIDs can cause adverse reactions, mainly gastrointestinal damage. Omeprazole (OMP) exhibits gastroprotective activity, but its protection is limited at the intestinal level. For this reason, it is essential to utilize a combination of therapies that provide fewer adverse effects, such as the combined treatment of OMP and docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-inflammatory, analgesic, and gastroprotective activities. The objective of this study was to evaluate the pharmacological interaction between DHA and OMP in a murine model of indomethacin-induced gastrointestinal damage. The gastroprotective and enteroprotective effects of DHA (0.3-10 mg/kg, p.o.), OMP (1-30 mg/kg, p.o.), or the combination treatment of both compounds (3-56.23 mg/kg, p.o.) were evaluated in the indomethacin-induced gastrointestinal damage model (30 mg/kg, p.o.). Since DHA and OMP exhibited a protective effect in a dose-responsive fashion, the ED30 for each individual compound was determined and a 1:1 combination of DHA and OMP was tested. Isobolographic analysis was used to determine any pharmacodynamic interactions. Since the effective experimental dose ED30 (Zexp) of the combined treatment of DHA and OMP was lower than the theoretical additive dose (Zadd; p < .05) in both the stomach and small intestine their protective effects were considered synergistic. These results indicate that the synergistic protective effects from combined treatment of DHA and OMP could be ideal for mitigating damage generated by NSAIDs at the gastrointestinal level.
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Affiliation(s)
- Martha Ivonne Sánchez-Trigueros
- Laboratorio de Farmacología, Doctorado en Ciencias en Biotecnología, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Fidel Méndez-Cruz
- Laboratorio de Farmacología, Programa de Servicio Social en Investigación, Escuela Nacional de Medicina y Homeopatía (ENMyH) del Instituto Politécnico Nacional (IPN), Ciudad de México, Mexico
| | - Elizabeth Arlen Pineda-Peña
- Carrera Médico Cirujano, Facultad de Estudios Superiores Zaragoza, Campus I, Iztapalapa, Ciudad de México, Mexico
| | - Yadira Rivera-Espinoza
- Doctorado en Ciencias en Biotecnología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Gilberto Castañeda-Hernández
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados (Cinvestav) del Instituto Politécnico Nacional (IPN), Ciudad de México, Mexico
| | - Aracely Evangelina Chávez-Piña
- Laboratorio de Farmacología, Doctorado en Ciencias en Biotecnología, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México, Mexico.,Maestría en Ciencias en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México, Mexico
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DMARDs-Gut Microbiota Feedback: Implications in the Response to Therapy. Biomolecules 2020; 10:biom10111479. [PMID: 33114390 PMCID: PMC7692063 DOI: 10.3390/biom10111479] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/10/2020] [Accepted: 10/21/2020] [Indexed: 12/20/2022] Open
Abstract
Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.
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Grinevich VB, Kravchuk YA, Ped VI, Sas EI, Salikova SP, Gubonina IV, Tkachenko EI, Sitkin SI, Lazebnik LB, Golovanova EV. Management of patients with digestive diseases during the COVID-19 pandemic: Clinical Practice Guidelines by the Gastroenterological Scientific Society of Russia. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2020:4-51. [DOI: 10.31146/1682-8658-ecg-179-7-4-51] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
The presented clinical practice guidelines of the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The guidelines were approved by the XXIII Congress of the GSSR and the 22nd International Slavonic-Baltic Scientific Forum “St. Petersburg — Gastro-2020 ON-LINE” (St. Petersburg, June 11, 2020).
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Affiliation(s)
| | | | - V. I. Ped
- Military Medical Academy named after S.M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S.M. Kirov
| | | | | | | | - S. I. Sitkin
- State Research Institute of Highly Pure Biopreparations of FMBA of Russia; Almazov National Medical Research Centre; North-Western state medical University named after I.I. Mechnikov, Ministry of health of the Russian Federation
| | - L. B. Lazebnik
- FSBEI HE MGMSU named after A.I. Yevdokimov of the Ministry of Health of Russia
| | - E. V. Golovanova
- FSBEI HE MGMSU named after A.I. Yevdokimov of the Ministry of Health of Russia
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Abstract
PURPOSE OF REVIEW With the growing popularity and commercialization of probiotics, it is important to understand the implications of existing randomized controlled trials and their applicability in the clinical setting to treat luminal gastrointestinal diseases. RECENT FINDINGS Probiotics may be useful in the prevention of antibiotic-associated diarrhea, prevention of Clostridioides difficile infection and eradication of Helicobacter pylori. Some evidence supports the use of probiotics in the treatment of ulcerative colitis, prevention and treatment of pouchitis and irritable bowel syndrome. Caution has to be exercised in immunocompromised and critically ill individuals. New society guidelines do not encourage probiotic use in gastrointestinal disorders with the exception of premature infants to prevent necrotizing enterocolitis. SUMMARY Despite burgeoning body of literature and wide acceptance by the public, a thorough understanding of efficacy and safety of probiotics is lacking. Uniform dosage, standardized clinical end points, personalization based on host microbial profile and longer duration of follow-up on the research front may help in the future in appropriate positioning of probiotics in health and disease.
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Affiliation(s)
- Abbinaya Elangovan
- Department of Internal Medicine-Pediatrics, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Monika Fischer
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA
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Dehydroandrographolide inhibits mastitis by activating autophagy without affecting intestinal flora. Aging (Albany NY) 2020; 12:14050-14065. [PMID: 32702668 PMCID: PMC7425474 DOI: 10.18632/aging.103312] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 04/28/2020] [Indexed: 12/21/2022]
Abstract
Mastitis can seriously damage the physical and mental health of lactating women. The use of antibiotics and anti-inflammatory drugs may damage the flora balance in lactating women. To alleviate mastitis in lactating women and reduce drug-induced damage to the flora, we found that dehydroandrographolide (Deh) has good anti-inflammatory and bacterial balance functions. In vivo, we found that Deh significantly inhibited the expression of MPO, IL6, IL-1β, TNF-α, COX2 and iNOS and reduced pathological damage to the mammary gland. The feces in the control and Deh groups were collected and sequenced for 16S flora. The results showed that Deh did not change the primary intestinal microflora composition of the two groups. In vitro, our study showed that Deh significantly inhibited the expression of IL6, IL-1β and TNF-α in the EpH4-Ev cell line. When an AMPK inhibitor was added, the anti-inflammatory effect of Deh was blocked. To further study the anti-inflammatory mechanism of Deh, we found that Deh significantly promoted autophagy through the phosphorylation of AMPK, Beclin and ULK1. In conclusion, our study found that Deh promoted autophagy and played an anti-inflammatory role by activating the AMPK/Beclin/ULK1 signaling pathway and did not affect intestinal flora.
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Grinevich VB, Kravchuk YA, Tkachenko EI, Pershko AM, Ped VI, Sas IE, Gubonina IV, Lazebnik LB, Stefanyuk OV. Features of management of patients with gastroenterological pathology in the conditions of the COVID-19 pandemic. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2020; 174:3-18. [DOI: 10.31146/1682-8658-ecg-176-4-3-18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Affiliation(s)
| | | | | | | | - V. I. Ped
- Military Medical Academy named after S. M. Kirov
| | - I. E. Sas
- Military Medical Academy named after S. M. Kirov
| | | | - L. B. Lazebnik
- FSEBI of HE “A. I. Evdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
| | - O. V. Stefanyuk
- FSEBI of HE “A. I. Evdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation, Federal State Budgetary Institution “National Medical Research Centre for Therapy and Preventive Medicine” of the Russian Ministry of Health
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Cervantes-García D, Bahena-Delgado AI, Jiménez M, Córdova-Dávalos LE, Ruiz-Esparza Palacios V, Sánchez-Alemán E, Martínez-Saldaña MC, Salinas E. Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress. Molecules 2020; 25:molecules25102351. [PMID: 32443501 PMCID: PMC7287897 DOI: 10.3390/molecules25102351] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/13/2020] [Accepted: 05/14/2020] [Indexed: 12/18/2022] Open
Abstract
Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.
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Affiliation(s)
- Daniel Cervantes-García
- Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (D.C.-G.); (A.I.B.-D.); (M.J.); (L.E.C.-D.); (V.R.-E.P.)
- National Council of Science and Technology, Mexico City 03940, Mexico
| | - Armida I. Bahena-Delgado
- Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (D.C.-G.); (A.I.B.-D.); (M.J.); (L.E.C.-D.); (V.R.-E.P.)
| | - Mariela Jiménez
- Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (D.C.-G.); (A.I.B.-D.); (M.J.); (L.E.C.-D.); (V.R.-E.P.)
| | - Laura E. Córdova-Dávalos
- Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (D.C.-G.); (A.I.B.-D.); (M.J.); (L.E.C.-D.); (V.R.-E.P.)
| | - Vanessa Ruiz-Esparza Palacios
- Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (D.C.-G.); (A.I.B.-D.); (M.J.); (L.E.C.-D.); (V.R.-E.P.)
| | - Esperanza Sánchez-Alemán
- Department of Morphology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (E.S.-A.); (M.C.M.-S.)
- Unit of Familiar Medicine #8, Mexican Institute of Social Security, Aguascalientes 20180, Mexico
| | - María C. Martínez-Saldaña
- Department of Morphology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (E.S.-A.); (M.C.M.-S.)
| | - Eva Salinas
- Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico; (D.C.-G.); (A.I.B.-D.); (M.J.); (L.E.C.-D.); (V.R.-E.P.)
- Correspondence: ; Tel.: +52-449-910-8424
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Chen XY, Fan HN, Zhang HK, Qin HW, Shen L, Yu XT, Zhang J, Zhu JS. Rewiring of Microbiota Networks in Erosive Inflammation of the Stomach and Small Bowel. Front Bioeng Biotechnol 2020; 8:299. [PMID: 32478040 PMCID: PMC7237573 DOI: 10.3389/fbioe.2020.00299] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 03/20/2020] [Indexed: 12/12/2022] Open
Abstract
The development of non-invasive, inexpensive, and effective early diagnosis tests for gastric and small-bowel lesions is an urgent requirement. The introduction of magnetically guided capsule endoscopy (MGCE) has aided examination of the small bowel for diagnoses. However, the distribution of the fecal microbiome in abnormal erosions of the stomach and small bowel remains unclear. Herein, alternations in the fecal microbiome in three groups [normal, small-bowel inflammation, and chronic gastritis (CG)] were analyzed by metagenomics and our well-developed method [individual-specific edge-network analysis (iENA)]. In addition to the dominant microbiota identified by the conventional differential analysis, iENA could recognize novel network biomarkers of microbiome communities, such as the genus Bacteroide in CG and small-bowel inflammation. Combined with differential network analysis, the network-hub microbiota within rewired microbiota networks revealed high-ranked iENA microbiota markers, which were disease specific and had particular pathogenic functions. Our findings illuminate the components of the fecal microbiome and the importance of specific bacteria in CG and small-bowel erosions, and could be employed to develop preventive and non-invasive therapeutic strategies.
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Affiliation(s)
- Xiao-Yu Chen
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Hui-Ning Fan
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Huang-Kai Zhang
- Aginome-XMU Joint Laboratory, Xiamen University, Xiamen, China
| | - Huang-Wen Qin
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Li Shen
- Clinical Research Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xiang-Tian Yu
- Clinical Research Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Jing Zhang
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Jin-Shui Zhu
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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Rekatsina M, Paladini A, Cifone MG, Lombardi F, Pergolizzi JV, Varrassi G. Influence of Microbiota on NSAID Enteropathy: A Systematic Review of Current Knowledge and the Role of Probiotics. Adv Ther 2020; 37:1933-1945. [PMID: 32291647 PMCID: PMC7467482 DOI: 10.1007/s12325-020-01338-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Indexed: 12/25/2022]
Abstract
Microbiota are increasingly studied, providing more precise information on their important role in physiologic processes. They also influence some pathologic processes, such as NSAID-induced enteropathy. This side effect is much more diffuse than it has been described in the past. It derives mainly from the local action of the medicines and is caused by the local binding of gram-negative bacterial lipopolysaccharides and infiltration of neutrophils into the intestinal mucosa. The initial interest in the interaction between these damages and microbiota is very old, but new and interesting data are available. This review aims to focus on recent studies on NSAID-induced enteropathy, an often-underestimated medical condition, and on the influence of microbiota on this condition. Apart from the broadly investigated use of antibiotics and other mucosal protective solutions, this systematic review focuses mostly on the use of probiotics, which directly influence intestinal microflora. Other important factors influencing NSAID-induced enteropathy, such as sex, advanced age, infection and use of proton pump inhibitors, are also discussed.
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Affiliation(s)
| | - Antonella Paladini
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Building Delta 6, 67100, L'Aquila, Italy
| | - Maria Grazia Cifone
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Building Delta 6, 67100, L'Aquila, Italy
| | - Francesca Lombardi
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Building Delta 6, 67100, L'Aquila, Italy
| | | | - Giustino Varrassi
- Paolo Procacci Foundation, Via Tacito 7, 00193, Rome, Italy.
- World Institute of Pain, Winston Salem, NC, USA.
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Watanabe T, Fujiwara Y, Chan FKL. Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review. J Gastroenterol 2020; 55:481-495. [PMID: 31865463 PMCID: PMC7188723 DOI: 10.1007/s00535-019-01657-8] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 12/10/2019] [Indexed: 02/04/2023]
Abstract
Recent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.
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Affiliation(s)
- Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
| | - Francis K L Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
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Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs in the world, and their side effects are very high. First of all, these are NSAID gastropathy, but in the long term, 5070% of NSAIDs cause damage to the small intestine (NSAID enteropathy), sometimes with serious consequences. To date, no drugs have been proposed with proven effectiveness to prevent this side effect. Apparently, this is not due to the fully clarified mechanism of pathogenesis. The most promising is the hypothesis of the participation of individual representatives of microflora in the development of enteropathy. Therefore, modulating the intestinal flora with the help of probiotics can be the basic therapeutic strategy for the prevention and treatment of such damage.
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Affiliation(s)
- E N Kareva
- Sechenov First Moscow State Medical University (Sechenov University).,Pirogov Russian National Research Medical University
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Zhu S, Li H, Liang J, Lv C, Zhao K, Niu M, Li Z, Zeng L, Xu K. Assessment of oral ciprofloxacin impaired gut barrier integrity on gut bacteria in mice. Int Immunopharmacol 2020; 83:106460. [PMID: 32248021 DOI: 10.1016/j.intimp.2020.106460] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 03/13/2020] [Accepted: 03/28/2020] [Indexed: 12/18/2022]
Abstract
Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.
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Affiliation(s)
- Shengyun Zhu
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, China
| | - Huiqi Li
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China
| | - Jing Liang
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China
| | - Chaoran Lv
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China
| | - Kai Zhao
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, China
| | - Mingshan Niu
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, China
| | - Zhenyu Li
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, China
| | - Lingyu Zeng
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, China
| | - Kailin Xu
- Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, China.
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Nardosinanone N suppresses LPS-induced macrophage activation by modulating the Nrf2 pathway and mPGES-1. Biochem Pharmacol 2020; 173:113639. [DOI: 10.1016/j.bcp.2019.113639] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 09/12/2019] [Indexed: 12/13/2022]
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Maseda D, Ricciotti E. NSAID-Gut Microbiota Interactions. Front Pharmacol 2020; 11:1153. [PMID: 32848762 PMCID: PMC7426480 DOI: 10.3389/fphar.2020.01153] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/15/2020] [Indexed: 12/21/2022] Open
Abstract
Nonsteroidal anti-inflammatory drugs (NSAID)s relieve pain, inflammation, and fever by inhibiting the activity of cyclooxygenase isozymes (COX-1 and COX-2). Despite their clinical efficacy, NSAIDs can cause gastrointestinal (GI) and cardiovascular (CV) complications. Moreover, NSAID use is characterized by a remarkable individual variability in the extent of COX isozyme inhibition, therapeutic efficacy, and incidence of adverse effects. The interaction between the gut microbiota and host has emerged as a key player in modulating host physiology, gut microbiota-related disorders, and metabolism of xenobiotics. Indeed, host-gut microbiota dynamic interactions influence NSAID disposition, therapeutic efficacy, and toxicity. The gut microbiota can directly cause chemical modifications of the NSAID or can indirectly influence its absorption or metabolism by regulating host metabolic enzymes or processes, which may have consequences for drug pharmacokinetic and pharmacodynamic properties. NSAID itself can directly impact the composition and function of the gut microbiota or indirectly alter the physiological properties or functions of the host which may, in turn, precipitate in dysbiosis. Thus, the complex interconnectedness between host-gut microbiota and drug may contribute to the variability in NSAID response and ultimately influence the outcome of NSAID therapy. Herein, we review the interplay between host-gut microbiota and NSAID and its consequences for both drug efficacy and toxicity, mainly in the GI tract. In addition, we highlight progress towards microbiota-based intervention to reduce NSAID-induced enteropathy.
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Affiliation(s)
- Damian Maseda
- Department of Microbiology, University of Pennsylvania, Philadelphia, PA, United States
| | - Emanuela Ricciotti
- Department of Systems Pharmacology and Translational Therapeutics, and Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States
- *Correspondence: Emanuela Ricciotti,
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Karateev AE, Moroz EV, Kryukov EV. Small intestinal damage associated with the use of nonsteroidal anti-inflammatory drugs. ALMANAC OF CLINICAL MEDICINE 2019; 47:559-567. [DOI: 10.18786/2072-0505-2019-47-048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
The use of nonsteroidal anti-inflammatory drugs (NSAID), even if short-term, may be associated to small intestinal complications, such as erosions, ulcers and chronic mucosal inflammation. Video capsule endoscopy allows for identification of such lesions in 20 to 55% of the patients who have taken nonselective NSAID for 2 to 4 weeks. The pathophysiology of NSAID-induced enteropathy is related to a reduced reparative potential of the mucosa and abnormalities of the microbial balance in the small intestine. In real world practice, NSAID enteropathy is commonly asymptomatic, and its manifestations, such as bleeding, perforation and ileus, are quite rare (about 0.3 episodes per 100 patient-years). The main manifestation of NSAID enteropathy is chronic iron deficient anemia. The use of rebamipide, sulfasalazine, mesalazine, and rifaximin has been discussed in the treatment of NSAID enteropathy, whereas its prevention implies preferential administration of coxibs, the use of rebamipide and probiotics.
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Affiliation(s)
- A. E. Karateev
- V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences
| | - E. V. Moroz
- N.N. Burdenko Main Military Clinical Hospital
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